Main Recurrent Translocations Involving The IgH Locus
\\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.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
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.
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6762",leadTitle:null,fullTitle:"Advances in Testosterone Action",title:"Advances in Testosterone Action",subtitle:null,reviewType:"peer-reviewed",abstract:"This book describes recent findings on androgens. The chapters include information on physiological and pathological conditions such as alteration in testosterone production by Leydig cells, prostate cancer, and metabolic disorders. Moreover, this book refers to the potential use of androgens in assisted human reproduction treatments and bovine breeding. Since each chapter contains background information based on evidence and emphasizes basic science, this book is aimed at professionals who already have a basic understanding of the principles of androgen biochemistry and endocrine-related diseases.",isbn:"978-1-78984-513-6",printIsbn:"978-1-78984-512-9",pdfIsbn:"978-1-83881-694-0",doi:"10.5772/intechopen.72493",price:119,priceEur:129,priceUsd:155,slug:"advances-in-testosterone-action",numberOfPages:118,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c7bfdea5f2e1d85ba08b6f07b8d3af5a",bookSignature:"Manuel Estrada",publishedDate:"November 21st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6762.jpg",numberOfDownloads:6581,numberOfWosCitations:9,numberOfCrossrefCitations:8,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:12,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:29,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2018",dateEndSecondStepPublish:"March 2nd 2018",dateEndThirdStepPublish:"May 1st 2018",dateEndFourthStepPublish:"July 20th 2018",dateEndFifthStepPublish:"September 18th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"29615",title:"Dr.",name:"Manuel",middleName:null,surname:"Estrada",slug:"manuel-estrada",fullName:"Manuel Estrada",profilePictureURL:"https://mts.intechopen.com/storage/users/29615/images/system/29615.jpg",biography:"Manuel Estrada received his PhD degree in Biomedical Sciences from Universidad de Chile in 2003. From 2003 to 2006, he served as a Postdoctoral Fellow at the Department of Pharmacology, Medical School at Yale University. Since 2006 he has been an Associate Professor of Physiology at the Department of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile. His research interests include rapid androgen effects and cardiomyocyte metabolic adaptations to hypertrophy. He is an author of many papers published in international peer-reviewed journals, and his presence is often requested as an Invited Speaker in congresses and diverse scientific meetings.",institutionString:"University of Chile",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Chile",institutionURL:null,country:{name:"Chile"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1014",title:"Reproductive Endocrinology and Infertility",slug:"medicine-endocrinology-reproductive-endocrinology-and-infertility"}],chapters:[{id:"62442",title:"Morphological Bases of Human Leydig Cell Dysfunction",doi:"10.5772/intechopen.79201",slug:"morphological-bases-of-human-leydig-cell-dysfunction",totalDownloads:1134,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, we describe the histophysiology of human Leydig cells, their cytological characteristics, their differentiation processes, and the physiopathological processes occurring at various times throughout life. We first focus on the normal development of fetal Leydig cells as well as the pathologies of fetal Leydig cells that can affect numbers or hyperplasic processes (e.g., hypogonadotropic hypogonadism, cryptorchidism, congenital Leydig cell hyperplasia secondary to diabetes, and isoimmunization). Next, we explain the changes occurring at puberty with the onset and differentiation of adult Leydig cells and the pathophysiology of delayed puberty. We then describe the histophysiology of adult Leydig cells and the most frequent pathologies (e.g., hypogonadotropic hypogonadism, testicular dysgenesia, mild androgen insensitivity syndrome, 5-α-reductase defect, and Klinefelter syndrome). Finally, we discuss the morphological changes of these cells in the elderly.",signatures:"Maria P. De Miguel, Pilar Gonzalez-Peramato and Manuel Nistal",downloadPdfUrl:"/chapter/pdf-download/62442",previewPdfUrl:"/chapter/pdf-preview/62442",authors:[{id:"199960",title:"Dr.",name:"Maria P",surname:"De Miguel",slug:"maria-p-de-miguel",fullName:"Maria P De Miguel"},{id:"248353",title:"Prof.",name:"Manuel",surname:"Nistal",slug:"manuel-nistal",fullName:"Manuel Nistal"},{id:"248354",title:"Dr.",name:"Pilar",surname:"Gonzalez-Peramato",slug:"pilar-gonzalez-peramato",fullName:"Pilar Gonzalez-Peramato"}],corrections:null},{id:"60839",title:"The Regulation of the Male Hypothalamic-Pituitary-Gonadal Axis and Testosterone Production by Adipokines",doi:"10.5772/intechopen.76321",slug:"the-regulation-of-the-male-hypothalamic-pituitary-gonadal-axis-and-testosterone-production-by-adipok",totalDownloads:1226,totalCrossrefCites:7,totalDimensionsCites:8,hasAltmetrics:0,abstract:"There is evidence that the mass and metabolic status of the adipose tissue that produces adipokines significantly affect the activity of the hypothalamic-pituitary-gonadal (HPG) axis and the synthesis of testosterone. This is due to the fact that adipokines, such as leptin, adiponectin, visfatin and resistin have an important role in the regulation of the male HPG axis and steroidogenesis in the testes. The regulation of the HPG axis by adipokines can be carried out both through the changes the plasma levels of adipokines (a systemic regulation) and through the changes in the expression and activity of adipokines in the pituitary and testes, the components of the HPG axis (an autonomous regulation). This review presents the comprehensive analysis of the involvement of leptin, adiponectin, resistin and visfatin in the regulation of the male HPG axis and the testosterone production, as well as of the possible mechanisms of this regulation. The role of adipokines in the dysregulation of the male reproductive system and the impaired steroidogenic activity in the testes in obesity and type 2 diabetes mellitus are also discussed.",signatures:"Alexander O. Shpakov, Julian R. Ryzhov, Andrey A. Bakhtyukov and\nKira V. Derkach",downloadPdfUrl:"/chapter/pdf-download/60839",previewPdfUrl:"/chapter/pdf-preview/60839",authors:[{id:"75888",title:"Dr.",name:"Alexander",surname:"Shpakov",slug:"alexander-shpakov",fullName:"Alexander Shpakov"},{id:"81685",title:"Dr.",name:"Kira",surname:"Derkach",slug:"kira-derkach",fullName:"Kira Derkach"},{id:"245240",title:"Mr.",name:"Julian",surname:"Ryzhov",slug:"julian-ryzhov",fullName:"Julian Ryzhov"},{id:"245241",title:"MSc.",name:"Andrey",surname:"Bakhtyukov",slug:"andrey-bakhtyukov",fullName:"Andrey Bakhtyukov"}],corrections:null},{id:"60756",title:"The Biological Role of Androgen Receptor in Prostate Cancer Progression",doi:"10.5772/intechopen.76360",slug:"the-biological-role-of-androgen-receptor-in-prostate-cancer-progression",totalDownloads:1897,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Prostate cancer is the most commonly diagnosed cancer in men all over the world. Localized cancers in the early stages can be well managed by surgical or radiation therapy. Metastatic prostate cancer is treated with androgen deprivation therapy because androgen signaling is essential to the prostate tumor growth and anti-apoptotic ability. However, resistance develops quickly in the clinical course and leads to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) functions as a nuclear receptor to facilitate ligand-dependent transcriptional activation in the nucleus. AR interacts with several tissue-specific transcription factors such as forkhead box protein A1 (FOXA1) and regulates epigenetic status by recruiting epigenetic factors. In addition, AR transcriptional activity is modulated by interacting directly or indirectly with non-coding RNAs such as long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). Notably, enhanced AR signaling in CRPC has been documented in several studies; however, which of these factors are important for the biological function it remains poorly understood. Here, I review our current knowledge of the mechanistic roles of AR involved in prostate cancer progression and discuss the importance of the prostate cancer-associated signals.",signatures:"Ken-ichi Takayama",downloadPdfUrl:"/chapter/pdf-download/60756",previewPdfUrl:"/chapter/pdf-preview/60756",authors:[{id:"239221",title:"Dr.",name:"Ken-Ichi",surname:"Takayama",slug:"ken-ichi-takayama",fullName:"Ken-Ichi Takayama"}],corrections:null},{id:"63382",title:"Effects of Dehydroepiandrosterone (DHEA) Supplementation to Improve Ovarian Response and IVF Outcomes on Women with Poor Ovarian Response",doi:"10.5772/intechopen.79320",slug:"effects-of-dehydroepiandrosterone-dhea-supplementation-to-improve-ovarian-response-and-ivf-outcomes-",totalDownloads:1207,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"There is still no clear consensus on the poor responder (PR) definition, however, the European Society of Human Reproduction and Embryology (ESHRE) suggested, in 2011, the Bologna criteria, which includes, for a poor ovarian response definition, at least two of the following three characteristics: age > 40 years, the number of oocytes previously recovered equal to or less than three, and low ovarian reserve tests score. It is noticed that, despite the use of different effective ovulation stimulation protocols, clinical pregnancy rates remain low in PR. In recent years, however, many authors, including Casson et al., reported the beneficial of DHEA supplementation on ovarian response in this group. Dehydroepiandrosterone (DHEA), a precursor of estradiol (E2) and testosterone (T), originates from the reticularis adrenal zone and from ovarian theca cell. In this chapter, we intend to demonstrate the potential benefits of DHEA supplementation in women with poor response in IVF outcomes.",signatures:"José Fernando de Macedo, Maristela Rodrigues Oliveira and Olga\nGoiana Martins",downloadPdfUrl:"/chapter/pdf-download/63382",previewPdfUrl:"/chapter/pdf-preview/63382",authors:[{id:"115594",title:"Mr.",name:"José",surname:"Macedo",slug:"jose-macedo",fullName:"José Macedo"},{id:"248124",title:"Mrs.",name:"Maristela",surname:"Oliveira",slug:"maristela-oliveira",fullName:"Maristela Oliveira"},{id:"248125",title:"Mrs.",name:"Olga",surname:"Sampaio",slug:"olga-sampaio",fullName:"Olga Sampaio"}],corrections:null},{id:"61362",title:"Influence of Testosterone on Body and Testicular Development in Zebu Cattle in the Tropical Climate",doi:"10.5772/intechopen.76706",slug:"influence-of-testosterone-on-body-and-testicular-development-in-zebu-cattle-in-the-tropical-climate",totalDownloads:1119,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The Brahman cattle is mainly used for breeding and the meat industry. The present chapter had the objective of evaluating the physical and testicular development, and the serum testosterone level of 8–18 months old male Brahman cattle on grazing weight gaining performance tests. In Bos indicus, puberty usually occurs between the ages of 16 and 18 months. Variables such age, weight, and scrotal circumference were equally important in the estimation of sexual maturity in male Bos indicus. An increase in serum testosterone level occurred between 12 and 14 months of age, followed by testicular and body growth. An elevation in testosterone levels is an indicator that an acceleration in physical and testicular growth is approaching. The variables body weight and scrotal circumference which are important in the estimation of sexual maturity are dependent on testosterone levels in zebu cattle according to literature. It is recommended to calculate body mass index and testicular volume to follow male growth due to the high correlation between these variables.",signatures:"Marcelo Chacur, Alex Arikawa, Eunice Oba, Camila Souza and Luis\nRoberto Gabriel Filho",downloadPdfUrl:"/chapter/pdf-download/61362",previewPdfUrl:"/chapter/pdf-preview/61362",authors:[{id:"239524",title:"Prof.",name:"Marcelo George",surname:"Chacur",slug:"marcelo-george-chacur",fullName:"Marcelo George Chacur"},{id:"245222",title:"MSc.",name:"Alex",surname:"Arikawa",slug:"alex-arikawa",fullName:"Alex Arikawa"},{id:"245223",title:"MSc.",name:"Camila",surname:"Souza",slug:"camila-souza",fullName:"Camila Souza"},{id:"245224",title:"Dr.",name:"Eunice",surname:"Oba",slug:"eunice-oba",fullName:"Eunice Oba"},{id:"245225",title:"Dr.",name:"Luis Roberto",surname:"Gabriel Filho",slug:"luis-roberto-gabriel-filho",fullName:"Luis Roberto Gabriel Filho"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"805",title:"Sex Steroids",subtitle:null,isOpenForSubmission:!1,hash:"69b8296a72c662d5d96bf61a1b394eda",slug:"sex-steroids",bookSignature:"Scott M. 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\r\n\tThis book on "Soldering - New Techniques and Approaches" will intend to provide a comprehensive discussion into the diverse topics in soldering and modern interconnection technology. One of the goals of the book will be to bridge this gap while moving from conventional to advanced lead-free soldering technology. Recent developments in high-density interconnection require the development of cost-effective and lightweight miniaturized devices such as flip-chip packages and through Si via technology. The micro joining of these miniaturized appliances needs low-cost interconnect materials and approaches in a practical scenario. The evolution of microelectronic devices and circuits towards drastic miniaturization and high density-high speed platforms for rapid data processing necessitates the development of new advanced and reliable solder materials. The usage of conventional Sn-Pb solders has been now regulated worldwide due to the various toxicity issues and directives, i.e., the Restriction of Hazardous Substances (RoHS), Waste Electrical and Electronic Equipment (WEEE), and End-of-Life Vehicles (ELV). This book will aim to cover a broad overview of modern soldering and micro joining materials and new technologies developed over the years in this discipline.
",isbn:"978-1-80356-747-1",printIsbn:"978-1-80356-746-4",pdfIsbn:"978-1-80356-748-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"a4b9a00a0b9b0718ef37413d53a5c146",bookSignature:"Dr. Ashutosh Sharma",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11940.jpg",keywords:"Materials, Conventional Soldering, Modern Soldering, Shear Strength, Wetting, Intermetallic Growth Kinetics, Fracture Toughness, Solder Pastes, Solder-Joints, Wire Bonding, Flip Chip Packages, Metallization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 25th 2022",dateEndSecondStepPublish:"June 1st 2022",dateEndThirdStepPublish:"July 31st 2022",dateEndFourthStepPublish:"October 19th 2022",dateEndFifthStepPublish:"December 18th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A pioneering scientist in the field of advanced microelectronic packaging and fabrication technologies, holder of Extraction and Processing Division (2016) Award, TMS USA, and 17 registered patents and several publications.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"145236",title:"Dr.",name:"Ashutosh",middleName:null,surname:"Sharma",slug:"ashutosh-sharma",fullName:"Ashutosh Sharma",profilePictureURL:"https://mts.intechopen.com/storage/users/145236/images/system/145236.jpeg",biography:"Ashutosh Sharma is currently working in the Department of Materials Science and Engineering, Ajou University, Suwon, South Korea. He earned his Ph.D. degree in Metallurgical and Materials Engineering from the Indian Institute of Technology (IIT) Kharagpur, India. His research interests include electrochemical deposition, lead-free soldering and brazing, additive manufacturing, high entropy alloys, gas sensors, and composites. Dr. Sharma is a life member of various scientific and professional bodies. In a very short time, he has contributed more than 100 international journals, 17 patents, 8 book chapters, and 1 authored book, and 1 edited book so far. 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The M-Ig can be an intact immunoglobulin (Ig) (containing both heavy and light chains), or light chains in the absence of heavy chain (encountered in light chain myeloma, light chain deposition disease, AL amyloidosis), or rarely heavy chains in the absence of light chains only (heavy chain disease).
All intact Igs have the same structure, made up of mirror imaged identical light and heavy chains. There are five classes of heavy chain, γ, α, μ, δ and ε with two classes of light chain κ and λ. Igs are secreted by terminally differentiated B-lymphocytes and their normal function is to act as antibodies recognizing a specific antigen.
During B-cell maturation, the rearrangement of Ig heavy and light chain genes takes place early in pre-B-cell development and ends in memory B-cells or Ig producing plasma cells that have a unique heavy and light chain gene rearrangement, thus being selected to recognize a given antigen. During, oncogenic events which occur randomly during this process, the B cell may acquire a survival advantage, and proliferate into identical (clonal) daughter B-cells able to differentiate into Ig producing cells secreting a monoclonal component. With additional oncogenic events a mature B-cell neoplasm may develop, carrying the inherent ability to produce a monoclonal Ig. Multiple myeloma and Waldenstrom’s macroglobulinaemia are architypical of Ig-secreting B-cell disorders.
The purpose of this present chapter is to describe the properties of M-Igs and discuss the biologic, clinical and other implications of their presence in the course of B-cell disease entities.
B-cell maturation is a complex process that comprises both cell differentiation into Ig secreting plasma cells and, in parallel, the rearrangement of the genes responsible for Ig synthesis. Furthermore it includes inherent risks of genetic derailment because it is associated with DNA remodelling with intrinsic instability, thus presenting the possibility of malignant development.
B cell development begins in the bone marrow (BM) from gestation week 18 and throughout life. The generation of pro-B cells from a common lymphoid progenitor cell depends on two main transcription factors, E12 and E47 and on the contribution of the transcriptional regulators EBF and Pax-5 [5]. During B-cell evolution the rearrangement of Ig heavy and light chain genes takes place [2]. The Ig heavy gene (IgH) is located on chromosome 14 while Ig light chain (IgL) genes are on chromosomes 2 and 22 for κ (1-40 vκ, 1-5 jκ and 1cκ) and λ (1-30 vλ, 1-4 jλ and 1-4cλ) light chain respectively. Rearrangement of IgH and IgL genes allows variable (V), diversity (D) and joining (J) gene segments rearrangement. V(D)J recombination starts in precursor B cells (pre B-I); recombinase activating genes 1 and 2 (RAG-1 and RAG-2), are essential for this step. The resulting IgVH is frequently not functional therefore the pre-B cell initiates V(D)J recombination at the other allele. If this is successful, the complete IgVH will be expressed as an Igμ H chain in the cytoplasm (Cy-Igμ) and on the membrane, together with a surrogate light chain, the pre B cell receptor complex (pre-BCR). Accordingly the pre-B-II cell proliferates, then looses its pre-BCR and re-express RAG proteins [7]. At that point, the B-cell is transformed into a small pre B-II cell that will subsequently rearrange the IgL variable gene segments and expresses a mature membrane BCR. If the BCR is not strongly self-reactive, the immature B cell leaves the BM as transitional B cell that evolves into naive B cell in the spleen; alternatively, it may mature in the periphery. However, if the immature B cell is still self-reactive, it will remain in the BM for additional IgVL recombination, replacing the self-reactive IgVL by another IgVL and so on. B cells producing self-reactive BCRs are removed from the repertoire during maturation by BM silencing mechanisms [3;4]. Splenic transitional B cells (CD27- CD5+ CD10+ CD24hi CD38hi and L-selectinlo) undergo differentiation into mature naive B2, also called follicular (FO) B cells, or marginal zone (MZ) B cells [5]. The aforementioned B-cell population is characterized by limited proliferative capacity and survival upon BCR stimulation; it comprises less than 2% of the peripheral B cells [6]. While maturating in the spleen, transitional B cells loose CD10 and CD5 and start expressing higher levels of L selectin and CD44. Following which the B cell transforms into conventional naive B2 cells that recirculate via the blood to the secondary lymphoid tissues or organs [7]. MZ cells could represent the normal counterpart of marginal zone lymphoma cells and CD5+ B-cells the one of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). Blood also contains a small normal population of naive CD5+ CD27- cells that frequently produce poly-/self-reactive antibodies (Abs) [8]. The CD5 molecule negatively regulates BCR signals [9] and CD5 B cells represent 50% of poly-/self-reactive cells [10].
Lymph node (LN) colonization depends on the expression of L-selectin and integrin αLβ2 (LFA-1), while recruitment to mucosa-associated lymphoid tissues (MALT) depends on expression of L-selectin and integrin α4β7. Without antigenic stimulation, the naive B cells recirculate again.
Activation of mature naive B cells into Ig secreting plasma cells can be T-helper independent (TI) and antigen free, via invariant receptors (TI-1), or derives from crosslinking of the BCR by polyvalent Ags (TI-2). More frequently, it is performed in close collaboration with CD4-expressing T cells (T-helper dependant: TD), and results from a monovalent Ag aggression. MZ B cells of the spleen and other mucosal sites, mostly respond to TI-2 Ags, such as polysaccharides of bacterial cell walls and other bacterial components, able to crosslink BCRs [11]. IgM+ MZ B cells that are CD27+ are memory cells while CD27- are naïve; their BCRs display poly- and self- reactivity.
Schematic of B-cell Maturation and B-Lymphoproliferative Disorders Origin
T-helper-cell dependent (TD) B-cell activation takes place in germinal centers (GC) in response to the presence of free Ags, as part of immune complexes or at the surface of Ag presenting cells (APC). B-cells then differentiate into short-lived, Ab-forming plasma cells or proliferate as centroblasts expressing CD10+, CD38+ and BCL-6. These centroblasts express low amounts of the BCR at their surface and undergo somatic hypermutations (SHM), by accumulating nucleotide substitutions in their Ig variable (
Terminally differentiated B cells become either Ab-producing mature plasma cells that home to the bone marrow or memory cells [18]. Memory B cells (CD27+) are Ag-selected B cells, derived from TD GC responses and usually express either IgM- IgD- or IgM+ IgD+, comprising about 20% of all peripheral B cells. A small percentage of IgM only (IgM+ IgD-) and IgD only (IgM- IgD+) also exists. IgD-only B cells have undergone a Cμ deletion due to a non-canonical CSR event, express Igλ, contain extremely high levels of somatic IgV mutations [19] and show a strongly biased V3-30 IgVH gene usage [20], that can be seen in some malignant B-cell disorders [2]. Memory B-cells are long-lived, prone to Ig class switch (to IgG, IgA or IgE) and contain hypermutated IgV genes. Following stimulation, they present a competitive advantage over naive B cells in rapidly transforming themselves into plasma cells producing high affinity, class switched, IgG/IgA Abs [21]. They may hide in BM niches and recirculate numerous times. It is believed that in most indolent B-cell lymphoproliferative disorders, a proneoplastic condition precedes where the precursor neoplastic B-cell circulates and recirculates as a memory cell.
Where one or more oncogenic events occur during B-cell maturation, the resulting daughter cell will be identical and, if it has the ability to differentiate into an Ig producing cell, it will secrete a monoclonal component. Consequently, all B-cell mature neoplasms [22] have a common origin as well as the inherent ability to produce a monoclonal Ig.
Malignant B-cell Non-Hodgkin’s lymphoma (NHL) possibly develops because risks for genetic derailment are increased during SHM and CSR that are associated with DNA remodelling. Thus, the initiating steps of the malignant B-cell transformation concern erroneous V(D)J rearrangement. Recurrent translocations involving the IgH or IgL locus and observed in B-cell lymphoproliferative disorders are shown in table 1, in relation to their biologic repercussions in disease entities concerned.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
MCL/MM | \n\t\t\tt(11;14) | \n\t\t\tCyclin D1 encoded by CCND1 | \n\t\t\tRegulator of CDKs CDK4/CDK6 required for cell cycle transition G1→S | \n\t\t
FL | \n\t\t\tt(14;18) | \n\t\t\tBcl2 | \n\t\t\tAntiapoptotic | \n\t\t
MM | \n\t\t\tt(4;14) | \n\t\t\tFGFR3 | \n\t\t\tSignal transduction, pathways activation, cell proliferation regulation & differentiation | \n\t\t
MM | \n\t\t\tt(6;14) | \n\t\t\tCyclin D3 | \n\t\t\tCell cycle: G1→S transition | \n\t\t
MM | \n\t\t\tt(14;20) | \n\t\t\tMAFB | \n\t\t\tTranscription factor, lineage specific hematopoiesis regulation | \n\t\t
MM | \n\t\t\tt(14;16) | \n\t\t\tc-MAF | \n\t\t\tCell cycle Stimulation. Promote interactions of tumor & stromal cells | \n\t\t
BL/MM | \n\t\t\tt(8;14) | \n\t\t\tmyc | \n\t\t\tTranscription factor, cell proliferation, differentiation, apoptosis, stem cell self renewal | \n\t\t
Main Recurrent Translocations Involving The IgH Locus
Monoclonal gammopathy of undetermined significance (MGUS) is a pro-neoplastic condition that may evolve into multiple myeloma (MM) or other B-cell lymphoproliferative disorders. MGUS represent a first step in the development of monoclonal diseases while the progression of MGUS to MM or other entities may be secondary to a random second genetic event. Several studies indicate that the majority of IgH locus aberrations reported in MM are already present in MGUS, favoring the hypothesis that these are early genetic events in the progression leading to MM [23].
In MM, the most frequent partners in reciprocal translocations involving the IgH locus on chromosome 14q32, are 11q13 (15%), 4p16 (5%), 16q23 (5%), 21q12 (2%) and 6p21 (2%); two additional partners are also found rarely 12p13 (<1%) and 8q24 (<1%). Thus, the aforementioned translocations may deregulate seven oncogenes involved, CCND1, CCND2, CCND3, MAF, MAFB, MAFA and FGFR3/MMSET [24]. The overall rate of 14q32 translocations increases with disease progression and reaches 90% in advanced tumors. Light chain translocations are rather rare in MM, particularly Igκ, which seem to be very infrequent [25]. Changes in the expression of gene subsets could be partly responsible for disease heterogeneity, as well as for further disease transformation. Moreover, with the 11q13 partner, constitutive upregulation of cyclin D1 results, deregulating the cell cycle [26]; t(11;14) is accompanied with a higher frequency of CD20 expression, hyposecretory disease and λ light chain usage. This subtype is increasingly encountered in AL amyloidosis, with or without MM, and in the rare IgM MM and is associated with favorable outcome. Translocation t(4;14)(p16;q32), is cryptic because of its telomeric location [27] and has been associated with IgA isotype, λ chain usage, deletion or monosomy of chromosome 13, immature plasma morphology, more aggressive disease and shortened survival. It leads to deregulation of fibroblast growth factor receptor 3 (FGFR3) gene on der(14) and of Multiple Myeloma SET (MMSET) domain gene on der(4); the latter may be a critical transforming event. t(4;14) was found characterized by deregulation of chromatin organization, actin filament and microfilament movement [28].
The t(14;16)(q32;q23) leads to the dysregulation of the c-maf oncogene; it is more frequently encountered in IgA isotope and is associated with chromosome 13 deletion whereas t(14;20)(q32;q11) results in maf-B deregulation that like c-maf is a basic zipper transcription factor. The clinical significance of these rare IgH translocations is unknown and under investigation. However, the oncogenic process is continually going on during disease course and secondary IgH translocations can be observed such as those involving the myc oncogene (8q24), that are associated with advanced and aggressive disease. Especially in patients with cytogenetically high-risk disease, more changes are observed, including heterogeneous clonal mixtures with shifting predominant competitive clones [29].
It is interesting to observe that the abnormalities observed are not disease specific and can occur in different B-cell disorders in which they may confer different phenotypes, suggesting a role for additional factors [24].
A hallmark of Burkitt lymphoma (BL) is the expression of the myc oncogene, which has an essential role in cell proliferation, cell growth, protein synthesis, metabolism and apoptosis [30]. myc deregulated expression arises from t(8;14)(q24;q32), juxtaposing myc to the IgH locus, in 80% of cases, whereas in the remaining, myc is translocated to the κ- (2p12), or λ- (22q11) light chain respectively. In endemic BL, most myc/IgH breakpoints originate from aberrant somatic hypermutation, in contrast to sporadic cases where the translocation mostly involves the Ig switch regions of the IgH locus at 14q32. The discrepancies are perhaps due to differences in Epstein Bar Virus positivity between endemic and sporadic forms [31]. myc translocations are not completely specific for BL and have been reported in other B-cell entities.
Almost 70% of mantle cell lymphoma (MCL) patients are genetically characterized by the chromosomal translocation t(11;14). In several cases, patients also have point mutations and / or deletion of the ATM (ataxia telangiectasia mutated) gene. In addition, blastic forms or subtypes with more aggressive clinical behavior, may have additional mutations in genes that act as negative regulators of the cell cycle such as p16, p18 and p53 [32]. Rarer MCL cases are negative for cyclin D1, lack t(11; 14) and stand out of the usual clinical picture of MCL [33]; in such cases, cyclin D2 or cyclin D3 are overexpressed, a different permutation t(2; 12) (p12; p13) which connects cyclin D2 to the IgL-k locus may be present; it does not cause loss or quantitative disorder of genetic material, but at a molecular level, reconnecting two chromosomal regions can disrupt important genetic sequences, causing inactivation or gene mutation. Moreover, in this permutation, the protooncogene PRAD1 (Parathyroid Adenomatosis 1, or bcl1) which is normally found on chromosome 11, is swapped in the heavy chain Ig gene on chromosome 14 [34]. The resulting oncogene bcl1/IGH encodes cyclin D1 that is an important cell cycle regulator, particularly during the transition from the G1 to the S phase (the same applies for cyclins D2 and D3). Under normal conditions, cyclin D1 acts through its interaction with cyclin dependent kinases (CDKs). CDKs are enzymes that add phosphate groups to protein-targets in order to make them inactive. The resulting complexes CDK4-D1 and CDK6-D3, promote the progress to cell cycle phase S, resulting in an uncontrolled proliferation.
Follicular lymphoma (FL) is characterized by the presence of chromosomal translocation t(14;18), which promotes protein bcl2 overexpression that in turn, leads to the suspension of apoptosis and survival increment of B cells that harbor the translocation. Less commonly, bcl2 is deregulated by translocation to the Igκ t(2;8) and Igλ t(8;22) loci [35]. The t(14;18) is apparently mediated by the RAG recombinase proteins, which cleave at J segments in the IgH locus and at an unusual non B form DNA structure in bcl2. These B cells undergo an epigenetic reprogramming which, in conjunction with the acquisition of additional events, leads to FL development. The t(14;18)(q32;q21) may also be observed in diffuse large B cell lymphoma (DLBCL) [36] and in non-gastric MALT lymphomas. It brings the MALT1 gene under the control of the IGH enhancer [37].
The IgH locus contains a region of 40-50 functional variable (VH), 27 diversity (DH) and 6 joining (JH) gene segments which is flanked by exons encoding the Ig constant regions (Cμ, Cδ, Cγ3, Cγ1, Cα1, Cγ2, Cγ4, Cε and Cα2). The Igκ locus contains 34-38 functional Vκ and 5 Jκ gene segments and one exon encoding the constant region of Igκ (Cκ). The Igλ locus comprises 29-30 functional Vλ and 4 functional Jλ-Cλ combinations [16]. Consequently, one of about fifty functional VH, another of thirty D, and one of six JH genes and, in the same way, one of thirty VL and one of four JL genes will be used. It appears that there are nearly 200 functional heavy and light chain gene segments that give rise to combinations of gene products, allowing the production of more than 5 × 107 antibodies with different unique variable end antigen combining sites [15;38;39]. Independently of the initiating stimulus, partly due to the aberrant Ig locus translocations and the putative activation or silencing of genes in monoclonal diseases, the cell starts to synthesize Ig following the variable domain rearrangement. On the coding DNA strand, the gene segments for the formation of the variable and the constant domains of the heavy chain are in order 5´ VDJ-μ-δ-γ3-γ1-α1-γ2-γ4-ε-α2- 3´. The RNA polymerase binds to the template strand of DNA and starts reading in 3´ to 5´ direction adding nucleotides to the 3´end of pre-mRNA transcript. Alternative splicing of the pre- mRNA brings together the VDJ variable domain and constant domain segments leading to the formation of the mRNA heavy Ig chain. As this procedure occurs in order, initially VDJs will get together with μ constant domain leading to the synthesis of heavy IgM component. This will bind with a light chain forming an IgM molecule. Thus, in order, cells make at first IgM, then IgD, IgG3, IgG1, IgA1, IgG2, IgG4, IgE and IgA2 that consist of the same variable domains but different constant domains due to alternative splicing and giving them different specific properties [40].
Light chains are synthesized in parallel to the heavy chain partner. However, an excess of light chains is produced, that if remained unbound to a heavy Ig component, will enter the blood and the extravascular compartment and circulate as free light chains (FLC). In patients with plasma cell dyscasias (PCD) and B-cell lymphoproliferative disorders, homogeneous serum total Ig molecules (intact Ig) and serum FLCs (sFLCs) are secreted by the malignant clone [40].
sFLCs are rapidly cleared (2-6hrs) and metabolized by the kidney although trace quantities (1-10mg/L) can be found in the urine, produced by the lower urinary tract mucosa. With regard to intact Ig, IgA and IgM are cleared by pinocytosis and have constant half lives of 5-6 days while IgG has a concentration dependent variable half life, ranging from days to weeks or even months. Briefly, IgG is ingested by reticulo-endothelial cells by pinocytosis, but inside the endosome, it is bound by a recycling receptor called neonatal (FcRn) receptor and recycled back to the surface to be released. This process can occur many times and extends the half lives of both IgG and albumin, as FcRn binds to both IgG, via the constant domain, and albumin non-competitively [40]. When there is a large amount of IgG (as can be found in diseases such as IgG MM) the receptor becomes saturated and the half life of IgG is shorter.
Antibodies are the secreted form of the BCR, the simple symmetrical structure is conserved through the 5 immunoglobulin classes which are defined by their heavy chain amino acid sequences (γ, α, μ, δ and ε) although in MM IgM, IgD and IgE monoclonal proteins are rare. There is further subclass division for γ (γ1, γ2, γ3, γ4) and α (α1 and α2) immunoglobulin classes. Amino acid sequence analysis of the 5 immunoglobulin classes showed that each was based upon the same repeating structure, 2 identicial light chains (~25kDa in size, 211-217 amino acids) and 2 identical heavy chains (~50kDa in size, 450-550 amino acids depending upon the class of heavy chain). Each of the immunoglobulin constituent proteins are constructed of β pleated sheets, which form the β barrel (Figure 2, A κ FLC molecule showing the constant region (left), and the variable region (right) with its alpha helix (red). (Courtesy of J Hobbs). Whilst there are obvious similarities between the different classes of immunoglobulin these structures are still being resolved and understood. IgG can be divided into 3 subunits, two identical fragment antigen binding arms (Fab) and an crystallizable (Fc) stem. Furthermore, within each subclass the hinge region shows differences both in the number of amino acids and the flexibility of the protein. More elegant electron tomography imaging of this molecule clearly shows its globular nature which perhaps gives a better indication of the protein structure. Serum IgA is predominantly a monomer, but dimeric forms can be found with J chain linkers. Solution scattering modelling of the two subclasses suggests a structure similar to IgG for IgA2 immunoglobulins, however IgA1 proteins appear to have a flattened “T” shaped structure. The traditional 2 dimensional representation of immunoglobulins belies their globular and highly variable nature, which may wrongly support the assumption that such molecules are simply quantified.
β pleated sheets of the kappa free light chain
In normal conditions, the Ig or Ab (antibody) recognizes a unique part of the foreign target or antigen, called an epitope [40;41]. Each tip of the "Y" of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly. Antibodies contribute to immunity in three ways: they prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating the pathogens; and they trigger their destruction by stimulating other immune responses such as the complement pathway [42-44].
The five major Ab classes present complementary functions are shown in Table 2.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
IgM | \n\t\t\tMain Ig during Primary Response (Early antibody). Fixes Complement (most effectively). | \n\t\t
IgG | \n\t\t\tMain Ig during Secondary Response (late antibody). Opsonization. Fixes Complement. Neutralizes Toxins, Viruses. | \n\t\t
IgA | \n\t\t\tSecretory mucosal Ig Prevents invasion from gut mucosa. | \n\t\t
IgE | \n\t\t\tImmediate Hypersensitivity. Mast cell and Basophil reactions. Activates Eosinophils in helminth infection. | \n\t\t
IgD | \n\t\t\tFunction Unknown. Mostly on the Surface of B cells (B cell receptor). | \n\t\t
Major Functions of Antibodies Classes
Monoclonal Igs are not secreted after antigen exposure and do not contribute to combat pathogens; in fact humoral immunity is impaired because monoclonal plasma cells proliferate in detriment of normal Igs. Thus, in B-cell lymphoproliferative disorders, profound polyclonal hypogammaglobulinaemia can be observed leading to the inability to fight infections.
In some cases, the monoclonal Ig can have other effects, such as the ability to agglutinate red cells (cold agglutinin disease), to act as auto-antibody (autoimmune haemolytic anaemia), to aggregate at low temperatures (cryoglobulinemia), cause increased viscosity (Waldenstrom’s macroglobulinemia), to deposit in tissues with resulting organ dysfunction (AL amyloidosis or immunoglobulin deposition diseases), and to cause peripheral neuropathy (MGUS, WM, AL amyloidosis, POEMS syndrome) [45].
Monoclonal intact immunoglobulin is routinely detected by serum protein electrophoresis (SPEP), the heavy chain class identified by immunofixation (IF) and quantified by SPEP-densitometry or nephelometry. Guidelines recommend SPEP to monitor monoclonal immunoglobulin concentrations as markers of response and relapse. However, SPEP quantification can be inaccurate at low concentrations (10g/L), can be difficult when the M-Ig co-migrates with other serum proteins (commonly IgA and IgM isotypes), when monoclonal immunoglobulins are produced by multiple small clones and is not suitable for sFLC quantification. Furthermore, poor linearity of SPEP at high concentrations and the variable catabolism of monoclonal IgG can make assessment of the serum load inaccurate. To aid patient monitoring international guidelines (IMWG 2011 concensus) recommend the use of total Ig nephelometric assays. At gross concentrations these assay are suitable tools to monitor patients; however, as they are unable to distinguish between the monoclonal and polyclonal Igs they will be insensitive as the Ig concentration approaches the normal range. One potentially useful addition to the laboratorian’s armatorarium to overcome these issues are the newly developed heavy / light chain (HLC) immunoassays targeting the unique junctional epitope between the light chain (CL) and heavy chain (CH1) constant region of immunoglobulin, enabling the separate quantification of the different immunoglobulin classes i.e. HLC-IgGκ, -IgGλ, -IgAκ, -IgAλ, -IgMκ and -IgMλ. Measuring the molecules in pairs with this method enables the calculation of a ratio of the involved/uninvolved-polyclonal Igs (HLCR) [46-48] in the same manner as sFLC κ/λ ratios (FLCR).
SPEP quantification of sFLC is inaccurate and for more than 150 years monoclonal FLC measurements relied upon urinalysis. Collection, handling, renal function and variable light chain biochemistries make this a less than ideal medium for analysis. In the last 10 years the introduction of sheep based, polyclonal immunoassays for the quatification of sFLC κ and λ have changed the paradigm for FLC measurement. Briefly, polyclonal sheep antisera target κ and λ epitopes that are not available when the light chains are bound to their heavy chain partners [49]. As previously discussed FLCs are not homogeneous proteins and have significant genetic differences, particularly in the case of λ FLC, making the use of polyclonal antibodies (rather than monoclonal) necessary to ensure recognition of all FLC clones. The paired tests enable quantification of sFLC within and below the normal range which leads to the identification of subtle monoclonal clones [87], below the sensitivity of SPEP and the qualitative IFE methods.
Intact Ig molecules, due to their size, are not filtered and excreted in the urine. Their presence in urine indicates glomerular damage and is usually part of the nephrotic syndrome that can accompany some monoclonal diseases (amyloidosis). If a simple urinalysis to identify protein in the urine gives a positive result, a 24-hour urine collection is required for urine IF. On the contrary, sFLCs that are much smaller, are freely filtered, excreted in the urine and metabolized in the urinary tract. During the initial stages of a plasma cell disorder, they are produced in small amounts that are entirely filtered by the urinary system; the majority is metabolized while small amounts may be excreted in the urine. Consequently, a negative serum IF may result while urine protein electrophoresis and IF may be positive. Urine test is not required for follow up due to the “paralogue phenomenon “of the sFLC. As the disease progresses the sFLC cause renal damage and decreased excretion from the kidneys leading eventually to decreased levels in the urine. If only urines are tested for follow up, low levels of sFLC could be found leading, in case of relapse, to wrongly consider disease improvement. In addition, during treatment, the reversal of renal damage will cause more excretion of sFLC to the urine, finding that should not be interpreted as disease progression.
Monoclonal Ig, as measured by total Ig quantification, or more recently FLC or HLC, may contribute to diagnosis, response evaluation, disease monitoring or prognostication in plasma cell dyscrasias and B-cell lymphoproliferative disorders (Table 3).
Contribution of Total Ig, sFLC/sFLCR and HLC/HLCR Measurements In Plasma Cell Dyscrasias and B-cell Lymphoproliferatiive Disorders.
√:useful, -: not useful, ?: unknown, √D-S: for Durie and Salmon Staging, *If present at diagnosis,** IgM level is included in the IPSS-WM, ***when abnormal sFLCR is observed, its evaluation is useful; ⊥included in recently proposed CLL staging [50].
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell dyscrasia that is present in more than 3% of the general white population older than age 50. It has an average multiple myeloma progression risk of about 1% per year [51]. The entity was first described by Waldenstrom in 1960 after abnormal narrow hypergammaglobulinemia bands were noted in the serum of healthy individuals on SPEP [52]. In 1978, Kyle introduced the term “monoclonal gammopathy of undetermined significance” after observing that asymptomatic patients with monoclonal protein have a higher risk of developing multiple myeloma, Waldenstrom macroglobulinemia, light-chain amyloidosis or related disorders [53]. Since then definition of MGUS has undergone several adaptations but always, paraprotein presence represented the backbone of its characterization.
In the updated 2010 IMWG diagnostic criteria, the definition of MGUS includes the presence of a serum monoclonal protein <3 g/dL, <10% clonal BM plasma cells infiltration and absence of end-organ damage (CRAB criteria of multiple myeloma) [54].
Over the last years, 3 distinct clinical subtypes of MGUS have been recognized: non-IgM MGUS, IgM MGUS and light-chain MGUS [55;56]. The best characterized MGUS subtype is non-IgM MGUS. Paraprotein isotypes of non-IgM MGUS patients can be further categorized into IgG (69%), IgA (11%) and biclonal (3%) [57]. Furthermore, IgD and IgE consist just a small portion of all non-IgM MGUS cases [51]. Malignant transformation of non-IgM MGUS approximates 1% per year and typically develops into multiple myeloma rather than lymphoproliferative disorders [57]. IgM MGUS accounts for about 17% of all MGUS cases. It tends to progress to Waldenstrom macroglobulinemia or other lymphomas [58]. Finally, light-chain MGUS is characterized by the absence of intact IgM protein and the presence of monoclonal FLC characterized by a skewed FLC ratio, due to the increased levels of the monoclonal FLC [59]. This last type is not frequently identified because asymptomatic patients are rarely tested with FLC assays; light chain MGUS’ frequency is estimated at about 20% of cases.
Based on available clinical markers, two major predictive risk models of MGUS progression have been established by the Mayo clinic and the Spanish study group [55]. The Mayo clinic model indentifies 3 major risk factors: abnormal sFLC ratio, presence of non-IgG monoclonal Ig and monoclonal protein ≥ 15 g/l [59]. At 20 years of follow-up, the absolute risk of progression for MGUS patients with 0, 1, 2, and 3 risk factors is 5%, 21%, 37% and 58% respectively [59]. The Spanish study group proposes multiparametric flow cytometry as a tool to indentify aberrant plasma cell populations [60]. In addition, a recent study [61] showed that suppression of uninvolved immunoglobulin in MGUS, as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression), is an independent risk factor for progression to malignancy. Uninvolved Ig suppression, occurring several years before malignant transformation takes place, offers a new perspective in early detection or even prediction of MGUS progression.
Monoclonal Ig is also the central marker used for MGUS patients follow-up. Moreover, patients should be followed performing SPEP, Ig and FLC quantification, at a frequency that depends on their risk-group.
Finally, special attention should be given to associations between MGUS and numerous diseases that are commonly encountered in clinical practice, because these may be related to underlying mechanisms with relevance in disease pathogenesis. In a retrospective cohort study of more than 4 million individuals, elevated risks of MGUS and MM were associated with broad categories of autoimmune, infectious, and inflammatory disorders but not allergies [62]. Systemic lupus erythematosus (SLE), a multisystem autoimmune disease characterized by profound B cell hyperactivity, autoantibody formation, and hypergammaglobulinemia, has been associated with MGUS, although the latter is not clearly a manifestation of disease activity and its significance remains to be elucidated [63]. Two possible mechanisms have been proposed for the aforementioned correlation of the two nosological entities. The first hypothesis claims that B cell hyperactivity in SLE favours the escape of B cell clones from the normal regulatory mechanisms. An alternative hypothesis is that defective immunological surveillance, predisposing to malignancies in general, promotes the development of MM and/or its precursor state MGUS. Concerning rheumatoid arthritis (RA), several studies have indicated a direct correlation of the disease with MGUS presence. More specifically, 1.7% of patients with classical RA and high-titre rheumatoid factor present with MGUS [64].
Multiple myeloma (MM) is an heterogeneous PCD with a wide range of clinical manifestations and outcomes, affecting terminally differentiated B-cells and characterized by bone marrow infiltration by monoclonal plasma cells secreting a monoclonal Ig. The disease might be asymptomatic, requiring only follow-up, or symptomatic and accompanied by fatigue, bone pains or spontaneous fractures, renal failure, recurrent infections or other morbid symptoms. In such cases treatment is immediately needed to prevent if possible irreversible organ damage. Paraprotein presence and amount are included into the diagnostic criteria [65-67]. The diagnostic criteria for smoldering (asymptomatic) multiple myeloma is a serum M protein level of ≥3g/dL, ≥10% BM plasma cells infiltration, and no related organ or tissue impairment (including bone lesions) or symptoms and the diagnostic criteria for symptomatic multiple myeloma is M protein (serum or urine) presence, BM plasma cell infiltration of ≥10% or histologically proven plasmacytoma, and myeloma-related organ or tissue impairment [68], further characterized by the CRAB criteria of multiple myeloma for end-organ damage, consisting of hypercalcemia (calcium level>11.5 mg/dL), renal failure (serum creatinine >2.0 mg/dL or estimated creatinine clearance <40 mL/min), anemia (hemoglobin level <10 g/dL or hemoglobulin level at least 2g/dL below the lower normal limit) and bone lesions (lytic lesions, severe osteopenia or pathologic fractures) [54]. sFLC measurements also are useful for diagnostic purposes, especially in light chain myeloma (LCM) and oligosecretory disease [69].
The evaluation of response to treatment is largely based on Ig decrease with complete response (CR) identified as negative IFE on both serum and urine, maintained for a minimum of 6 weeks [70]. In an attempt to improve response criteria, sFLCR was incorporated to the MM uniform response criteria [71] and its normalization along with immunohistological or immunophenotype confirmation of clonal disease absence, defined a deeper response, the stringent complete response (sCR). A better evaluation of the depth of response is important as the quality of response is correlated with treatment free and overall survival after treatment [72]. In the same way, relapse is established by an Ig increase on SPEP, total Ig quantification, sFLCs and more recently HLCs; all the aforementioned methods can therefore be used for disease monitoring [73]. An additional contribution of sFLC mesurements for disease monitoring during follow-up of patients is that light chain only relapses may be observed, with the improvement of treatment modalities resulting in prolonged survival. Disease transformation characterized by light chain escape may occur, characterized by a shift in secretion from intact Ig to LC only in a subset of patients [74;75] that could be otherwise considered in plateau.
With regard to prognosis, although serum monoclonal Ig quantification was one of Durie and Salmon staging system’s risk factors [76] and was included in older prognostic algorithms [77], it was subsequently not shown to be linked with MM aggressiveness and was not retained as a prognostic risk parameter [78]. However, paraprotein type was shown to influence survival; IgG patients being most favourable, followed by IgA while light chain MM patients had the worst prognosis [79]. The introduction of the new Ig-based biomarkers (sFLC/HLC) rehabilitate monoclonal Igs prognostic potential in MM. Thus, sFLC and sFLCR were shown predictive of outcome in all MM subcategories. Patients with smoldering myeloma and abnormal sFLCR were shown to have an increased progression risk while an adverse outcome was observed in patients with overt MM and increased sFLCR [80;81]. In addition, the combination of sFLCR and other markers of disease activity (LDH, β2-microglobulin, genetic abnormalities) or the International Score System (ISS) for MM, were reported to produce powerful prognostic models [78;82], although this is yet to be proven in the ear of novel therapies [83]. Furthermore three groups showed simultaneously that HLC-IgG and –IgA ratios (HLCR) were predictive of a shorter overall survival [73;84] and progression-free survival [85].
Systemic AL amyloidosis is characterised by the deposition of misfolded monoclonal light chains or their fragments in tissues or organs, leading to visceral dysfunction [86]. Symptomatology depends on the organ(s) involved and includes nephrotic syndrome, skin lesions, cardiomyopathy, demyelinating peripheral neuropathy, hepatomegaly, malabsorption syndrome, etc. Diagnosis is frequently difficult, in the (usual) absence of characteristic signs such as macroglossia or periorbital purpura. Physicians should be aware of the possible diagnosis of AL amyloidosis in patients with unexplained fatigue, and FLCR can aid in the differential diagnosis. In such a context sFLC measurements are useful and will be found increased in up to 94-98% of patients, even in the absence of any Ig monoclonal peak on serum electrophoresis or immunoelectrophoresis. However, diagnosis should be proven by involved tissue biopsy. Kidney is the most frequently involved organ while cardiac deposits are the most deleterious and related to shorter survival. AL amyloidosis may complicate MM or other PCD in less than 10% of cases.
sFLC levels concentrations at diagnosis are by themselves an adverse marker of survival in AL amyloidosis [88]. The addition of cardiac biomarkers to sFLC levels at diagnosis was shown highly predictive of patients survival [89] and a new prognostic staging system was built [90]; a score of 1 for each of three prognostic variables, namely cardiac troponin T (cTnT) (> 0.025 ng/mL, N-terminal pro–B-type natriuretic peptide (NT-ProBNP) (>1,800 pg/mL), and FLC difference (FLC-diff) (>18 mg/dL), was used to divide patients into four stages (I, II, III, and IV) with scores of 0, 1, 2, and 3, respectively. The 5-year survival estimates produced for patients in stage I, II, III, and IV were 59%, 42%, 20%, and 14% respectively (p<0.001).
Preliminary data on HLC measurements in AL amyloidosis appear promising. In a subset of AL amyloidosis patients with no detectable serum or urinary monoclonal bands and a normal sFLC ratio, the HLC ratio was abnormal in 19% of cases, identifying 2 IgAκ, 3 IgAλ, and 4 IgGκ clones [91].
Waldenstroms Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma (LPL) [22] characterized by lymphoplasmacytic infiltration of BM and eventually other organs, and by the presence of a serum IgM monoclonal component. IgM paraprotein is mandatory to establish the diagnosis. In case of a biology proven LPL without IgM, the disease will be called just LPL, not WM.
WM is a rare disease entity that presents a wide range of clinical signs and symptoms including those due to the lymphoma (lymph nodes’ swelling, organomegaly, bone marrow failure) and those due to the presence of the IgM paraprotein. IgM-related symptoms are hyperviscosity, autoimmune phenomena (peripheral neuropathy, haemolytic anaemia, thrombocytopenic purpura), cryoglobulinaemia, amyloidosis. Asymptomatic patients do not require treatment and usually enjoy a prolonged survival, while patients with aggressive symptomatic disease should be immediately treated with chemotherapy [92;93]. Evaluation of response is based on changes in serum IgM concentrations and other factors. Complete response (CR) is characterized by the disappearance of symptoms, of monoclonal serum IgM (by IF), and of monoclonal lymphoplasmacytes from all infiltrated sites, partial response by a serum IgM decrease by 50% or more while progressive disease (PD) by IgM increase; likewise, relapse after response is characterized by IgM increase [94]. With regard to staging and prognosis, serum IgM levels were included into currently used international prognostic staging system for WM (IPSS-WM) that co-evaluated 5 parameters: age above 65 years, haemoglobin below 11,5 g/dL, platelet counts below or equal to 100×109/L, β2-microglobulin above 3mg/L and IgM above 7 g/dL [95].
There are so far only preliminary results on the contribution of the new Ig-based biomarkers (sFLC and HLC) levels in WM patients at diagnosis. It was shown that sFLC may be increased and, in such cases, correlate with markers of disease activity, such as increased β2M, anemia [96] and low serum albumin levels. Patients with elevated sFLC presented shorter time to treatment [97] and adverse outcome [98]. Increased HLC-IgM were also found correlated with markers of disease activity such as bone marrow infiltration of more than 50% and low serum albumin levels while high HLCR correlated with shorter time to treatment [98;99].
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world and presents a large range of clinical manifestations and a variable outcome. More than two thirds of the patients are asymptomatic at the time of diagnosis and may not require treatment for months or even years. For prognostic purposes, traditional Rai and Binet clinical staging systems are still in use but they do not apply perfectly in modern years. For patients needing treatment, underlying molecular alterations are important predictors of response; however, for the majority of CLL patients, life expectancy largely depends on time to first treatment [100], so reliable markers for time to treatment are needed.
It was shown that increased sFLC is the most common paraprotein observed in CLL, being found in almost half of the cases and that sFLCR abnormalities are present in a significant proportion of patients and identify those at risk of progressive disease [101;102].
More recently, increased polyclonal sFLC were also found to constitute an adverse marker for time to first treatment in CLL [103]. This finding was confirmed by Morabito et al that evaluated the sum of κ and λ sFLC levels and found that the prognostic impact of sFLC (κ + λ) value above 60.6 mg/mL was superior compared to FLCR and built a model based on four variables, namely sFLC (κ + λ) more than 60.6 mg/mL, Binet staging, ZAP-70, and cytogenetics and separated 4 patients’ groups with different time to treatment [50].
In the other PCD, Ig contribution to diagnosis, prognosis and monitoring is restricted to bone solitary plasmacytoma and mainly concerns sFLC quantification that was shown predictive of evolution to MM [104]. With regards to B-cell non Hodgkin’s lymphomas, abnormal Ig secretion, as observed mostly by the new Ig-based biomarkers (sFLC and HLC) levels, the clinical significance of which remains for the time being, under investigation [105], although increasing evidence of sFLCs prognostic role are emerging in these diseases [106;107].
Paraprotein presence is the hallmark of monoclonality. Knowledge of biologic mechanisms that lead to monoclonality has allowed understanding of malignant B-cell origin and B-cell neoplasms pathophysiology. New methods for the precise detection and quantification of monoclonal Ig have opened interesting clinical applications concerning patients diagnosis, monitoring and prognostication.
Due to the rapidly growing number of manufacturing industries, toxic metal contamination in aquatic environments has gotten a lot of attention. Among the contaminants, heavy metals are targeted for major environmental concern because they are non-biodegradable, and they cannot be decomposed or metabolized [1]. Several metals cause serious health and environmental problems, and chromium (Cr) compounds are one of the most toxic contaminants in wastewater due to their high solubility and toxicity, as well as their free transferability [2].
Cr has been widely applied in a variety of industrial activities due to its excellent properties, including electroplating, leather tanning, nuclear power plants, and textile industries [3, 4]. Furthermore, it can be used for anodizing, corrosion control, and chemical manufacturing [5, 6, 7]. In a natural environment, Cr usually exists in two stable oxidation states: trivalent Cr(III) and hexavalent Cr(VI). Meanwhile, other oxidation states are not stable in aerated aqueous media [8]. Specifically for Cr(VI), it may exist in the form of CrO42− or HCrO4− in a natural aqueous environment, whereas Cr(III) is inclined to form [Cr(H2O)6]3+, Cr(H2O)5(OH)2+, Cr(H2O)4(OH)2+, or Cr(III) organic complexes.
Given its considerable risk to biological systems, many studies have focused on the removal of Cr(VI). Cr(VI) is highly toxic, carcinogenic, and mutagenic [8, 9]. Adverse health effects have been linked to Cr(VI) exposure, such as bronchitis, liver damage, kidney damage, brain damage, and even lung cancer. On the other hand, Cr(III) is the most stable form in reducing conditions and it exists as cationic species Cr(OH)2+ and Cr(OH)2+, with the first or second hydrolysis products dominating at pH values ranging from 4 to 8. Although Cr(III) is an essential microelement for the effective maintenance of mammal’s glucose, lipid, and protein metabolism [10], high doses of Cr(III) may cause negative consequences to the environment. Moreover, there are currently just a few articles on the adsorption of Cr(III). Therefore, the development of a recovery method for this metal (both Cr(III) and Cr(VI)) is significant from an environmental aspect.
Ion exchange, precipitation, ultrafiltration, reverse osmosis, and electro dialysis are one of the physical and chemical technologies that have been reported for the removal of heavy metals [11]. However, these procedures have some drawbacks, such as a high consumption of reagents and energy, low selectivity, high operational costs, and difficult further treatment due to toxic sludge production [12]. Adsorption is an effective method for removing metallic ions from aqueous solutions [10, 13]; and biological adsorption (biosorption) is one of the most environmentally friendly, cost-effective, recyclable, and technically simple methods [14, 15].
Among the many biosorbents available, chitosan can be an excellent biosorbent for metals because its amine (-NH2) and hydroxyl (-OH) groups may serve as coordination sites to form complexes with various heavy metal ions [16]. Chitosan, whose full chemical name is (1,4)-2-amino-2- deoxy-β-D-glucose, has been proven to be particularly effective as a biosorbent for the recovery of several toxic metals, including mercury (Hg), uranium (U), molybdenum (Mo), vanadium (V), and platinum (Pt) [17, 18, 19]. It can be employed as an environmentally friendly adsorbent because it is cost effective, and it does not result in secondary pollution. Chitosan is a polymer that is made via alkaline deacetylation of chitin, which comes from cellulose, the most abundant biopolymer. It can be acquired from the shells of seafood, such as prawns, crabs, and lobsters [20]. The biopolymer has a high nitrogen content, which is present in the form of amine groups, free amino groups, and hydroxyl groups, all of which are responsible for metal ion binding through chelation mechanisms [21].
Despite the uses of chitosan in the removal of various pollutants have been adequately reviewed [22], on the other hand, it has some defects, including notable swelling in aqueous media and nonporous structures, resulting in a very low surface area [23]. Therefore, a variety of chemical modifications can be used to produce chitosan derivatives that improve the removal efficiency of the heavy metal [24]. For example, to increase the number of exposed active sites, several chemical or physical modifications can be adopted [25, 26]. Moreover, since silicon dioxide has numerous properties, including rigid configuration, porosity, and large surface area, it can be employed to counteract the defects of chitosan. In addition, modified silicon dioxide has been produced through a graft between silanol groups and ligands [27, 28, 29]. In prior work, we synthesized a hybrid membrane of carboxymethyl chitosan and silicon dioxide as adsorbents for the removal of Cr(VI) [30]. Furthermore, we used epichlorohydrin (EP) and glutaraldehyde (GA) as cross-linked agents in an adsorption experiment of chromate ions onto cross- linked chitosan [31].
In this work, we evaluated the adsorption of chitosan modified with sodium dodecyl sulfate (SDS) as part of the adsorption study of Cr using modified chitosan. SDS-modified chitosan beads have been reported to be effective for removing cationic dyes [32]. Adsorption on surfaces is enabled by the metal ion strength and the presence of key functional groups on the polymer chain [33, 34, 35]. The particle aggregation via a bridging structure can be described as a two-step pathway: (1) initial chain adsorption and bridging, followed by (2) floc maturation/ reconfiguration. Before the interparticle connection occurs, the chain of SDS must be adsorbed on a chitosan surface [36]. Furthermore, chitosan modified with SDS has recently been used for the removal of heavy metals, such as cadmium [37, 38]. However, the use of SDS-modified chitosan as a Cr adsorbent, using different initial concentrations of SDS to optimize the adsorbent, has rarely been investigated. The objective of the present research is to determine the efficacy of SDS-modified chitosan beads as a sorbent for Cr(III) and Cr(VI) for future practical applications, as well as to understand the adsorption mechanism. After the characterization of SDS-chitosan by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and Fourier transform-infrared spectroscopy (FT-IR), batch experiments with SDS-modified chitosan beads were carried out to optimize the parameters and to obtain the maximum removal of Cr(III) and Cr(VI). In this study, we examined the effects of several parameters, including solution pH, contact time, adsorbent dosage, and initial concentration.
Chemical reagents, such as chitosan and sodium dodecyl sulfate (SDS; M.W.: 288.372 g/mol), were purchased from Tokyo Chemical Industry Co., Inc. Acetic acid, NaOH, HNO3, NaSO4, ethylenediaminetetraacetic acid disodium salt dihydrate, and toluene, were purchased from Kanto Chemical Industry Co., Inc. All reagents used were of analytical grade. During the whole working process in this study, the water (>18.2MΩ) treated by the ultrapure water system (RFU 424TA, Advantech Aquarius) was employed. K2CrO7 standard solution (1000 mg·L−1 from Kanto Chemical Co., Inc.) was diluted and used to prepare the Cr standard solution for calibration.
In this study, chitosan powder with a molecular weight (50–190 kDa) and degree of deacetylation (> 80%) was used. After drying, the viscosity of chitosan was 20 to 100 mPa·s (in 0.5%Acetic acid soln., 20°C). Firstly, 1.5 g of chitosan was placed in acetic acid solution (2.0%), and the solution was mixed for 24 h. The chitosan-gel was prepared by dropping the above chitosan solution into 200 mL of 0.20 mol·L−1 NaOH. Consequently, the obtained gel was rinsed with ultrapure water until its pH reached 7 after stirring for 24 h. Secondly, 200 tablets of chitosan-gel beads were placed in 100 mL of SDS solution (including the fixed concentration of SDS), and then left for five days. Thus, chitosan-gel beads modified with SDS were obtained, and finally, they were dried at 60°C overnight for use as an adsorbent. The synthesis procedure for the SDS-chitosan beads is demonstrated in Figure 1. It is considered that the prepared adsorbent has a bilayer of SDS over the surface of pure chitosan beads. This bilayer can have a higher ion capturing capacity [37].
Procedure employed for the synthesis of sodium dodecyl sulfate (SDS)-chitosan beads.
The diameter of chitosan beads was measured to be about 0.5–2 mm (judging from 200 beads as representative chitosan beads). After weighing 200 hydrogel beads, the dry weight per chitosan bead was estimated to be 3.7 × 10−4 g, which suggests that the adsorbent contained 98% moisture. In order to determine the physicochemical properties of pristine and modified chitosan, several characterization methods have been employed. FT-IR spectra of the samples were recorded in the range of 4000–500 cm−1 with a JASCO Japan FTIR-4200 spectrophotometer using KBr pellet pressing method. The surface morphology and element distribution of the chitosan beads before and after the adsorption of Cr were observed using SEM-EDS (JEOL Japan: JCM-6000 with JED-2300). X-ray Photoelectron Spectroscopy (XPS, Thermo Scientific Center: K-Alpha) was also used to assess the surface chemistry properties of SDS-modified chitosan beads.
The beads were put into contact with 50 mL of an aqueous solution containing Cr(III) or Cr (VI) ion with a known initial concentration. The pH of each solution was adjusted using 0.1 mol
where
Figure 2 shows the SEM-EDS images of the chitosan beads and SDS-chitosan. These images showed the unevenness of the surface. This was most likely due to the release of water from the adsorbent during the drying process of chitosan. In addition to the irregularities, SDS-chitosan showed a mesh-like pattern. This was thought to be due to SDS modified on the chitosan surface. In particular, the modified chitosan beads with a high SDS concentration stood out compared to the other beads. As the irregularities on the adsorbent’s surface were considered, the adsorption proceeded in two ways: physical and chemical adsorption. From the mapping images, it was proven that Cr ions were adsorbed onto the adsorbent surface.
Scanning electron microscopy (SEM) images of chitosan beads (a) and SDS-chitosan (b), and mapping images of SDS-chitosan after the adsorption of Cr(III).
The surface functional groups and the chemical compositions of the modified SDS-chitosan beads were identified by FTIR and XPS analysis, respectively. The FT-IR results of chitosan and cross-linked chitosan are shown in our previous work [39]. Figure 3 shows the FT-IR results of SDS-chitosan and the chitosan beads in this study, with the peaks of SDS-chitosan and the chitosan beads can clearly visible. It is apparent from this figure that the main peaks common to each adsorbent were due to the -OH group at 3400–3500 cm−1 and the aliphatic methylene group at 2871 cm−1. The amine and ether groups are shown by wide peaks at 1560–1640 cm−1 and 1110 cm−1, respectively. For SDS-chitosan, the peak at 1248 cm−1 was characteristic of the asymmetrical vibration of the C-O-S group, confirming that the prepared adsorbent was a composite of SDS and chitosan.
Fourier transform-infrared spectroscopy (FT-IR) spectra of chitosan and SDS-chitosan.
The chitosan beads with varying initial loading concentrations of SDS were analyzed using XPS, as shown in Figure 4. The C1s spectra of these samples displayed peaks at 284.5, 286.5, and 288.5 eV, corresponding to C-C, C-O, and C=O bonds, respectively. The S2p spectra of SDS600 and 6000-chitosan displayed peaks at 169 eV. The S that seemed to be derived from SDS was also not detected at SDS concentrations of 0 and 100 mg/L but was detected at concentrations of 600 and 6000 mg/L.
X-ray photoelectron spectroscopy (XPS) spectra of chitosan (a), SDS100-chitosan (b), SDS600-chitosan (c), and SDS6000-chitosan (d) beads.
To determine the optimum initial loading concentration of SDS for Cr(III) removal, the chitosan beads were modified with SDS solutions ranging from 10 to 9000 mg/L. The adsorption experiments were performed under the following conditions: an initial concentration of Cr(III) of 1 mg/L, a contact time of 2 days, and adsorbent dosage of 0.05 g, a pH of 4, and a temperature of 25°C. In the meantime, initial SDS concentrations were varied from 10 to 6000 mg/L for Cr(VI) removal. The experiment was performed under the following conditions: adsorbent dose of 0.05 g, initial concentration of Cr(VI) of 1 mg/L, pH of 4, and contact time of three days.
The results of Cr (III) adsorption are shown in Figure 5. The adsorption capacity continuously increased within 6000 mg/L as the SDS concentration increases, but the adsorption amount was almost constant at further higher concentrations. Thus, 6000 mg/L was the optimum initial loading SDS concentration for Cr(III). On the other hand, the adsorption capacity of SDS for the removal of Cr(VI) increased with an increase of the SDS concentration from 10 to 40 mg/L, and after that it decreased as shown in Figure 6. The maximum capacity for Cr(VI) was obtained at the initial SDS concentration of 40 mg/L.
Effect of the initial SDS concentrations on the adsorption of Cr(III).
Adsorption of Cr(VI) for different initial SDS concentrations (10–6000 mg/L). (a) Effect of initial SDS concentrations (10–6000 mg/L) on the adsorption of chromium (Cr) (VI). (b) Effect of initial SDS concentrations (10–1000 mg/L) on the adsorption of Cr(VI).
The effect of pH on Cr(III) adsorption by SDS-chitosan was investigated in the pH range of 4–7. Other parameters were set as the following: the contact time was 24 h, the temperature was 25°C, the adsorbent dosage was 0.4 mg/L, and the initial Cr(III) concentration was 1 mg/L. The results are shown in Figure 7. As shown in Figure 7, the adsorption capacity of Cr(III) increased with the increase of pH from 4 to 7. However, it was found that Cr (III) precipitated as Cr (OH)3 at the pH value in 6 and 7. Thus, a pH of 6 and 7 were not suitable for the adsorption experiments and optimized pH value was 4.
Effect of pH on the adsorption of Cr(III) by SDS-chitosan.
As for the adsorption experiment of Cr(VI), pH was set in the range of 4 to 10 (Figure 8). In this experiment, the shaking time was 24 h, the temperature was 25°C, and the dose of adsorbent was 0.02 g/L. As shown in Figure 8, pH affects Cr(VI) adsorption on SDS-modified chitosan beads. The acidity of the solution brought a significant effect on the adsorption of Cr(VI) on SDS-modified chitosan beads where the amino groups of the chitosan were protonated. Cr(VI) ions were most effectively adsorbed at pH 4–5, which may be related to changes in surface charge on the adsorbent. As pH increased above pH 5, the uptake decreased.
Effect of pH on the adsorption of Cr(VI) onto the SDS-modified chitosan beads.
The influence of contact time on the adsorption of Cr(III) by SDS-chitosan was investigated. The experiment was conducted under the following conditions: a pH of 4, a temperature of 25°C, an adsorbent dosage of 0.05 g, and an initial concentration of Cr(III) of 1 mg/L. Figure 9 shows that the adsorption capacity of SDS-chitosan for Cr (III) increased sharply within the first 24 h, and continued until the contact time reached 48 h. Thus, 48 h was selected as the optimized contact time.
Effect of contact time on the adsorption of Cr(III) by SDS-chitosan.
We have also studied how the contact time affects the adsorption capacities of SDS-modified chitosan beads towards Cr(VI) with varying contact times from 1 to 96 h (Figure 10). In this experiment, the concentration of Cr(VI) was set as 1 mg/L with the dose of 0.05 g at a temperature of 25°C adjusted pH to 4.
Effect of the contact time on the adsorption of Cr(VI) on the SDS-modified chitosan beads.
The adsorption capacity of SDS-chitosan beads for Cr(VI) increased sharply within the first 24 h, which may be attributable to the availability of the sites on the surface of the adsorbent. It is suggested that a concentration gradient is present in both the adsorbent and adsorbate in the solution [40]. Then, adsorption reached equilibrium at 72 h, and afterwards, there was no appreciable increase (Figure 10). Hence for further studies, the optimized contact time was taken as 72 h.
The adsorbent dosage is an important factor that affects the adsorption capacity. To study the effect of adsorbent dosage on the adsorption of Cr(III), adsorption experiments were conducted at a pH of 4, a temperature of 25°C, a contact time of 24 h, and an initial concentration of Cr(III) of 1 mg/L. The results are shown in Figure 11. The adsorption rate increased as the adsorbent dosage increased, reaching approximately 70% at 0.8 mg/L, after that, there was no appreciable increase. Thus, 1 mg/L was selected as the optimized adsorbent dosage.
Effect of the adsorbent dosage on the adsorption of Cr(III) by SDS-chitosan.
Meanwhile for the adsorption experiment of Cr (VI), 0.8 mg/L was regarded as the optimum dosage. The experiments were performed by varying the dosage (from 0.4 to 1.0 mg/L) and keeping all other parameters constant (temperature: 25°C; pH: 4; contact time: 24 h; initial concentration: 1.0 mg/L). The results are shown in Figure 12.
Effect of the adsorbent dosage on the adsorption of Cr(VI) on the SDS-modified chitosan beads.
In this study, adsorption experiments of Cr(III) were conducted in the presence of several competitive ions with different concentrations (0, 50, 100, and 200 mg/L) of Na+, Ca2+, Ba2+, K+, Mg2+, and Sr2+. The initial concentration of Cr(III) was set to 1.0 mg/L, the pH was 4, the temperature was 25°C, the contact time was 24 h, and the adsorbent dosage was 1.0 mg/L. The effect of competitive ions on the adsorption of Cr(III) is shown in Figure 13. It was confirmed that the adsorption capacity of Cr(III) did not decrease at all even in the presence of other metal ions.
The effect of competitive ions on the adsorption of Cr(III).
Conversely, it was found that Cr(VI) adsorption was inhibited when the concentrations of coexisting ions were high. The effect of competitive anions on the adsorption of Cr(VI) is shown in Figure 14. In this study, the initial concentration of Cr(VI) was fixed to 1 mg·L−1. These counter ions were tested collectively, and all the ions were included at 50, 100, or 200 mg/L in solution. From this figure, the removal of Cr(VI) was remarkably reduced under the presence of common ions at above 50 mg·L−1 (i.e., 50 times the Cr(VI) concentration or more), although no substantial decrease was observed when the concentration of each common ion was less than 10 mg·L−1 in our previous preliminary experiments.
Effect of competitive anions on the adsorption of Cr(VI) on the SDS-modified chitosan beads.
Adsorption isotherms describe the interactive process between the adsorbents and adsorbates in aqueous medium at the attained saturation point. Adsorption isotherms of Cr(III) and Cr(VI) on SDS-chitosan were identified with different initial concentrations from 0.01 to 2 mg/L under optimized conditions for the pH (4), contact time (48 h for Cr(III), 72 h for Cr(VI)), and dosage of the adsorbent (1 mg/L for Cr(III), 0.8 mg/L for Cr(VI)). The adsorption of Cr on SDS-chitosan was evaluated using typical adsorption isotherms, the Langmuir and Freundlich models (Figure 15 (a) and (b)).
The adsorption data obtained for Cr(III) using SDS-chitosan were analyzed by Langmuir and Freundlich equations (Figure 16 (a) and (b)).
Langmuir equation:
Freundlich equation:
where
The Langmuir isotherm model assumes that a monolayer adsorption occurs on the surface of an adsorbent. The slope of the linearized Langmuir isotherm can be used to explain the type of sorption using the Hall separation factor (
Metal T(K) | Langmuir Isotherm | Freundlich Isotherm | |||||
---|---|---|---|---|---|---|---|
Cr(III) | 298 | 3.42 | 1.15 × 10−3 | 0.842 | 1.41 | 1.21 | 0.820 |
Cr(VI) | 298 | 3.23 | 0.31 × 10−4 | 0.960 | 3.01 | 0.700 | 0.921 |
Isotherm parameters for Cr(III) and Cr(VI) adsorption onto SDS-chitosan.
As shown in Figure 16 (a), (b), and Table 1, it was revealed that the
The rate-controlling steps of the adsorption system are essential to survey the mechanism of Cr(III) and Cr(VI). Kinetic studies were conducted to explain the adsorption mechanism of Cr(III) and Cr(VI) ions onto the SDS-chitosan beads. The effects of contact time on the kinetics of Cr(III) and Cr(VI) adsorption by SDS-chitosan adsorbent are displayed in Figure 17 (a) and (b). According to Figure 17 (a), the removal of Cr(III) from SDS-chitosan increased sharply in the initial 6 h, indicating that the uptake of Cr(III) was primarily caused by chemical sorption. As shown in Figure 17 (b), the adsorption of Cr(VI) by SDS-chitosan beads increased significantly within 96 hours, although the increase continued at a slower rate for 48 h. The rapid adsorption within the initial 24 h indicated that Cr(VI) uptake was mainly dominated by chemical sorption or surface complexation.
To investigate the mechanism of adsorption of Cr(III) and Cr(VI) on SDS-chitosan, fitting was determined according to the pseudo-first-order (Figure 18 (a) and (b)), pseudo-second-order (Figure 19 (a) and (b)) and intraparticle diffusion kinetic models (Figure 20 (a) and (b)). The equations of these models are given by:
Pseudo-first-order model:
Pseudo-second-order model:
Intraparticle diffusion model:
where
The sorption kinetic parameters including
Metal | Pseudo-first-order model | Pseudo-second-order model | Intraparticle Diffusion | ||||||
---|---|---|---|---|---|---|---|---|---|
Cr(III) | 0.69 | 1.05 | 0.22 | 0.88 | 1.26 | 0.07 | 0.98 | 0.17 | 0.90 |
Cr(VI) | 1.09 | 1.04 | 0.06 | 0.99 | 0.88 | 0.13 | 0.99 | 0.09 | 0.99 |
Kinetic parameters of Cr(III) and Cr(VI) absorption onto SDS-chitosan.
After
The film diffusion coefficient
If
The pore diffusion coefficient
1.00 | 7.04 | 1.51 |
The film and pore diffusion coefficients of the adsorption.
It is also known that if the adsorption is controlled by the film diffusion, the values of the film diffusion coefficient may be in the range of 10−6
To explore the effect of temperature on Cr(III) adsorption by SDS-chitosan, adsorption experiments were performed at temperatures ranging from 298 to 318 K. The results are displayed in Figures 21 and 22. In these temperature ranges, the amount of Cr(III) adsorbed on SDS-chitosan increased with the increase of temperature.
Effect of temperature on the adsorption of Cr(III) onto SDS-chitosan.
Effect of temperature on the adsorption of Cr(VI) on the SDS-modified chitosan beads.
Furthermore, based on the experimental results, the thermodynamic parameters of the adsorption, such as standard Gibb’s free energy change
where
Table 4 and Table 5 indicate the thermodynamic parameters for Cr(III) and Cr(VI), respectively. In the temperature range of 298
298 | — | — | 0.855 |
308 | 12.0 | 37.4 | 0.481 |
318 | — | — | 0.107 |
Thermodynamic parameters for the adsorption of Cr(III) on SDS-chitosan.
T(K) | ΔH(kJ/mol) | ΔS(J/mol) | ΔG(kJ/mol) |
---|---|---|---|
288 | 80.70 | 288.18 | −2.34 |
298 | — | — | −5.22 |
308 | — | — | −8.10 |
318 | — | — | −10.98 |
Thermodynamic parameters for the adsorption of Cr(VI) on SDS-modified chitosan beads.
Repeated use of adsorbent and recovery of the adsorbed metal ions are important indicators for evaluating economic efficiency. In this study, regeneration experiments were carried out using the SDS-chitosan beads after adsorption of Cr(III) and Cr(VI). After adsorption, the spent adsorbent was treated with 50 ml of 0.1 mol/L NaOH solution and ultrapure water as desorption agent in desorption experiment, and then filtered. The content of Cr(III) and Cr(VI) in the filtrate was determined by ICP-MS [49]. Figure 23, Cr(III) by using NaOH or pure water, respectively. As can be seen in Figure 23, the desorption efficiency of Cr(III) was calculated as 57% when using 0.1 mol/L NaOH. The desorption of NaOH was larger than ultrapure water. This indicated that NaOH could be a desorption agent for Cr(III). As shows in Figure 24, the desorption efficiency of Cr(VI) was found to be 50% when 0.1 mol/L NaOH was used, and the desorption was considerably lower with H2O than NaOH. It is suggested that NaOH can be used as a desorption agent for Cr(VI), although a further investigation is needed for the effective recovery and recycling of Cr(VI).
Desorption efficiency of Cr(III) using NaOH or pure water.
The comparison of the maximum adsorption capacity of Cr(III) by SDS-chitosan in the present study with those of other adsorbents in the literature is presented in Table 6. As shown in Table 6, the adsorption capacity of SDS-chitosan for Cr(III) in this work was not necessarily high compared to other adsorbents. Meanwhile, Table 7 summarizes the comparison of maximum adsorption capacity of Cr(VI) on SDS-chitosan beads with other adsorbents. It can also be noted that the adsorption capacity is not so high compared to other adsorbents. However, it could be regarded as a potential adsorbent for treating Cr(III) and Cr(VI) from wastewater for practical usage because the synthesis method of the adsorbent is relatively simple.
Adsorbent | Adsorption capacity (mg | References |
---|---|---|
Vesicular basalt | 0.98 | [50] |
Chitosan | 1.67 | [51] |
Attapulgite | 11.0 | [51] |
Chitosan/attapulgite | 27.0 | [51] |
Crystalline hydrous titanium(IV) oxide | 14.0 | [52] |
Natural sepiolite | 0.53 | [53] |
Borax sludge | 4.00 | [54] |
SDS-chitosan | 3.42 | This study |
Comparison of adsorption capacity for Cr(III) by different adsorbents.
Adsorbents | Adsorption Capacity (mg·g−1) | Reference |
---|---|---|
Magnetic Chitosan | 69.4 | [14] |
Carboxymethyl Chitosan-Silicon Dioxide | 80.7 | [30] |
Chitosan-g-poly/silica | 55.7 × 10−3 | [55] |
Crosslinked chitosan bentonite composite | 89.1 | [56] |
Graphene oxide/chitosan | 86.2 | [57] |
Ethylenediamine-magnetic chitosan | 51.8 | [55] |
SDS-chitosan | 3.23 | This study |
The comparison of adsorption properties of several adsorbents.
Desorption efficiency of Cr(VI) using NaOH or pure water.
In this study, sodium dodecyl sulfate (SDS) was used to chemically modify chitosan to enhance its adsorption capacity for the removal of chromium. SEM-EDS, FT-IR, and XPS were used to characterize the SDS-chitosan beads. The effect of important operating parameters, such as the loading amounts of SDS, solution pH, contact time, adsorbent dose, temperature, and initial Cr(III) or Cr(VI) concentration, on the adsorption performance was examined in a batch system. The experimental data were found to be fit best using Langmuir isotherm and pseudo-first-order kinetic models. At pH 4–5 and higher temperatures, the adsorption process performed admirably. The maximum adsorption capacity of Cr(III) and Cr(VI) on SDS modified chitosan beads were estimated to 3.42 mg·g−1 and 3.23 mg·g−1, respectively in this work. Finally, the SDS-chitosan beads synthesized in this work can be effectively utilized to remove chromium successfully.
The authors are grateful to Mr. H. Morohashi of the Industrial Research Institute of Niigata Prefecture for the measurement of XPS and useful advice. The authors also thank Mr. M. Ohizumi of the Office for Environment and Safety, and Mr. N. Miyamoto, Dr. M. Teraguchi, Mr. T. Nomoto, and Prof. T. Tanaka, of the Facility of Engineering in Niigata University for permitting the use of ICP-AES, ICP-MS, FT-IR, and SEM-EDS.
The authors declare no conflict of interest.
The present work was partially supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Research Program (C), No. 21 K12290).
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However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",book:{id:"5609",slug:"phenolic-compounds-biological-activity",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Biological Activity"},signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",middleName:null,surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",middleName:null,surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",middleName:null,surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",middleName:null,surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",middleName:null,surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}]},{id:"45635",title:"Application of Cellulose and Cellulose Derivatives in Pharmaceutical Industries",slug:"application-of-cellulose-and-cellulose-derivatives-in-pharmaceutical-industries",totalDownloads:10348,totalCrossrefCites:60,totalDimensionsCites:138,abstract:null,book:{id:"3173",slug:"cellulose-medical-pharmaceutical-and-electronic-applications",title:"Cellulose",fullTitle:"Cellulose - Medical, Pharmaceutical and Electronic Applications"},signatures:"Javad Shokri and Khosro Adibkia",authors:[{id:"140056",title:"Prof.",name:"Javad",middleName:null,surname:"Shokri",slug:"javad-shokri",fullName:"Javad Shokri"}]},{id:"57200",title:"Introductory Chapter: Principles of Green Chemistry",slug:"introductory-chapter-principles-of-green-chemistry",totalDownloads:2816,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"6067",slug:"green-chemistry",title:"Green Chemistry",fullTitle:"Green Chemistry"},signatures:"Hosam El-Din Mostafa Saleh and M. Koller",authors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"},{id:"218817",title:"Dr.",name:"Martin",middleName:null,surname:"Koller",slug:"martin-koller",fullName:"Martin Koller"}]},{id:"66517",title:"Microbial Cellulases: An Overview and Applications",slug:"microbial-cellulases-an-overview-and-applications",totalDownloads:3563,totalCrossrefCites:42,totalDimensionsCites:91,abstract:"Cellulases are a complex group of enzymes which are secreted by a broad range of microorganisms including fungi, bacteria, and actinomycetes. In the natural environment, synergistic interactions among cellulolytic microorganisms play an important role in the hydrolysis of lignocellulosic polymer materials. In fact, it is the combined action of three major enzymes which determines the efficiency of this process. They are exoglucanases, endoglucanases, and β-glucosidase. Microorganisms produce these enzymes in a diverse nature which determines their efficiency in cellulose hydrolysis. During the cellulose degradation reaction, the enzyme targets the β-1,4-linkages in its polymeric structure. This is an essential ecological process as it recycles cellulose in the biosphere. The application of this same scenario for industrial purposes is identified as an emerging area of research. Biofuel production, textile polishing and finishing, paper and pulp industry, and lifestyle agriculture are among the key areas where cellulase enzyme shows a broader potential. The objective of this chapter is to discuss the structure, function, possible applications, as well as novel biotechnological trends of cellulase enzymes. Furthermore, possible low-cost, enzymatic pretreatment methods of lignocellulosic material in order to use it as an efficient raw material for biofuel production will be discussed.",book:{id:"7363",slug:"cellulose",title:"Cellulose",fullTitle:"Cellulose"},signatures:"Sandhya Jayasekara and Renuka Ratnayake",authors:null}],onlineFirstChaptersFilter:{topicId:"85",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"65119",title:"Introductory Chapter: Polyaniline - From Synthesis to Practical Applications",slug:"introductory-chapter-polyaniline-from-synthesis-to-practical-applications",totalDownloads:975,totalDimensionsCites:2,doi:"10.5772/intechopen.83397",abstract:null,book:{id:"7503",title:"Polyaniline - From Synthesis to Practical Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7503.jpg"},signatures:"Florin Nastase"}],onlineFirstChaptersTotal:1},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"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:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,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. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. 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. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. Barderas",slug:"oxidative-stress-in-cardiovascular-diseases",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",subseries:{id:"15",title:"Chemical Biology"}}}]},overviewPagePublishedBooks:{paginationCount:33,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. 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He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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