Upregulated miRNAs in CRC tumor tissue vs. normal tissue.
\r\n\tIn recent decades, numerous studies have been carried out on eukaryotic microorganisms viz., fungi, protozoa and algae to unravel the disease mechanisms caused by them and also their potential use in genetic engineering. The current book will accumulate the latest findings related to eukaryotic microorganisms in order to guide the future research and to uplift this area of microbiology for potential applications in medical and agricultural sciences.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"111dd972fdc98d1968c9f854910f7188",bookSignature:"Dr. Asghar Ali Kamboh",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8963.jpg",keywords:"Mycology, Protozoology, Phycology, Gut eukaryotic microbiota, Antifungal / Antiprotozoal agents, Manipulating the Genes of Eukaryotes, Use of Eukaryotes in genetic engineering",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 27th 2019",dateEndSecondStepPublish:"September 17th 2019",dateEndThirdStepPublish:"November 16th 2019",dateEndFourthStepPublish:"February 4th 2020",dateEndFifthStepPublish:"April 4th 2020",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"225390",title:"Dr.",name:"Asghar Ali",middleName:null,surname:"Kamboh",slug:"asghar-ali-kamboh",fullName:"Asghar Ali Kamboh",profilePictureURL:"https://mts.intechopen.com/storage/users/225390/images/system/225390.jpeg",biography:"Dr. Asghar Ali Kamboh was born in Mehrabpur, Sindh, Pakistan. He completed his studies in Veterinary Medicine and Masters in Veterinary Microbiology in 2003 and 2007 respectively, with distinguished grades. In 2009, he was awarded an overseas scholarship by the Government of Pakistan and proceeded to China for doctoral studies. Currently, he is working as an Associate Professor in the Department of Veterinary Microbiology, Sindh Agriculture University, Tandojam. He has edited two books and published more than 100 research and review articles in national and international peer-reviewed journals. He has supervised/co-supervised more than 35 M.Phil students. He is also the author of many books and book chapters. In addition, he is an editor/editorial board member of many scholarly journals in the area of animal health and production.",institutionString:"Sindh Agriculture University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Sindh Agriculture University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"13",title:"Immunology and Microbiology",slug:"immunology-and-microbiology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"305835",firstName:"Ketrin",lastName:"Polesak",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/305835/images/9351_n.png",email:"ketrin@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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In the last 20 years, its applications have been extended to large biological materials, such as proteins, DNA and membranes [1] and to healthy or diseased human tissue (e.g. cancer, atheromatic plaques, etc) [2, 3]. The technique is extensively used not only for organic compounds but almost all substances and is popular because it is simple, easy to perform, accurate and cost effective. It is hoped that in the very near future, affordable small IR instruments will be build to assist in fast pre-diagnosis and diagnosis, in clinical settings.
Functional groups like –CH2, -CH3, -NH, -OH, etc are easily identified from an IR spectrum and the material and biomaterial that contains them can be detected and conveniently compared with library spectra. Modern Fourier Transform Infrared (FT-IR) Spectrometers, can obtain an average of 100 to 150 spectra in the mid-infrared region, in a few seconds and with excellent resolution, a vast improvement from the past. FT-IR Spectrometers are now available at low cost (~€40,000) for the analytical chemist and the structural chemical spectroscopist. [4].
The aim of this book is to assist the chemist, spectroscopist and any other scientist interested in applying FT-IR. Presented herein are signature bands at high frequency regions (4,000-1,500 cm-1), capable of giving structural information [5-10]. The positions and intensities of the absorption bands can be used to characterize a compound from library spectra and to confirm the presence of a particular group in order to obtain information as to the structure and conformation of the molecule and its microenvironment. Skeletal vibrations of molecules (1,500-400 cm-1) can change substantially with conformational changes. However these should be used with caution and cannot be applied with a high degree of confidence to structural modifications taking place to large biomolecules. It is in assisting the IR spectroscopist in determining with confidence any particular identification and characterization of a molecule from “signature bands”, that this monograph aims to be of value.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/48234.pdf",chapterXML:"https://mts.intechopen.com/source/xml/48234.xml",downloadPdfUrl:"/chapter/pdf-download/48234",previewPdfUrl:"/chapter/pdf-preview/48234",totalDownloads:1602,totalViews:156,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:9,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:null,dateReviewed:"January 26th 2015",datePrePublished:null,datePublished:"March 4th 2015",dateFinished:"February 4th 2015",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/48234",risUrl:"/chapter/ris/48234",book:{id:"4474",slug:"infrared-spectroscopy-anharmonicity-of-biomolecules-crosslinking-of-biopolymers-food-quality-and-medical-applications"},signatures:"Theophanides Theophile",authors:[{id:"37194",title:"Dr.",name:"Theophile",middleName:null,surname:"Theophanides",fullName:"Theophile Theophanides",slug:"theophile-theophanides",email:"theophan@central.ntua.gr",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/37194/images/4237_n.png",institution:{name:"National Technical University of Athens",institutionURL:null,country:{name:"Greece"}}}],sections:[],chapterReferences:[{id:"B1",body:'According to the National Cancer Institute of The United States, cancer is defined as a disease in which cells grow uncontrollably and spread to other parts of the body [1]. Cancer can occur in any human tissue when cells lose control of cell division and multiply abnormally. Tumors, the accumulation of abnormal cells, can be limited to one location or invade into nearby tissues to form new tumors, a process known as metastasis. Cancerous tumors can be solid tumors, like colon cancer, or cancers of the blood, such as leukemias [1]. Regardless of the classification or tumor type, however; all cancers have common molecular features that have been identified as the hallmarks of cancer. These hallmarks encompass the biological abnormalities that are present in a cell to be classified as a cancer cell. They include the morphology, biology, metabolism, and genetic composition that are shared by all tumors.
The system used to organize the complexity of a cancer cell into simple hallmarks has been evolving for decades. Currently, there are 10 hallmarks of cancer. This includes self-sufficiency in growth signals, insensitivity to anti-growth signals, evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion, and metastasis, reprogramming energy metabolism and evading immune response, genome instability and mutation, and tumor-promoting inflammation [2]. Collectively, these characteristics arise from not only studying the biology but also assessing the genetic and genomic processes of cancer cells. For example, many hallmarks are common to both benign (non-cancerous tumors) and malignant growths, such as the evasion of apoptosis or cell death and limitless replication potential. Thus, it is only through genetic and genomic studies that the identification of additional markers provides evidence that cancer cells share the presence of genetic mutations and genomic instability. This approach is called the mutation theory and it argues that carcinogenesis is a process that initiates with genetic mutations that allow for the hallmarks of cancer to develop in a cell lifespan [3]. Therefore, we will summarize genetic factors that contribute to the hallmarks of cancer.
First, we will address the selective growth and proliferative advantage of cancer cells. Normal cells depend on growth signaling of a strictly regulated cell cycle to proliferate and maintain tissue homeostasis. On the other hand, in cancer cells, the growth and proliferative signals are altered by mutations in genes that code for growth ligands, receptors, and other survival-signaling molecules involved in apoptosis [4]. Depending on the biological role that they play in proliferation, growth factors can be upregulated or downregulated. Increased levels may enhance tumor progression, whereas, lower than normal levels may result in the escape of the tumor from regulation. A well-studied example is that of the transforming growth factor-β (TGF-β), which can be an anti-growth ligand but has also been implicated in tumor progression through stimulating differentiation of cancer cells. The duality of genes like TGF-β can be the result of gene amplification, somatic mutations, or chromosomal translocations that may lead to fusion proteins and aberrant signaling [4]. A more complex example is the rat sarcoma virus (RAS) protein, which is active in 30% of all cancers. This protein is often altered as the result of missense mutations in its gene or inactivating mutations in one of its negative regulators, resulting in a variety of effects such as enhanced growth and proliferation, suppression of apoptosis, rewiring of metabolism, promoting angiogenesis, and immune evasion. Thus, mutations in the
Similarly, another key regulator of cell growth is the tumor protein 53 (TP53), which is the most often mutated cancer gene, altered in over 50% of sequenced tumors. The main function of
In addition to unregulated growth and cell death, cancer cells can develop the potential to invade and proliferate outside their original tumor niche. Metastasis is the process that allows cancer cells to form secondary tumors and metastatic disease is responsible for over 90% of cancer-related deaths and involves several steps. For a cancer cell to become metastatic, it must invade through the extracellular matrix, promote angiogenesis and tumor vasculature, survive transport in circulation, and manipulate foreign microenvironments [7]. Most human carcinoma cells migrate collectively in an aberrant pattern. In the case of solid tumors, such as those seen in colon cancer, cancer evolves from epithelial cells that are normally immotile and tightly adherent to one another and the surrounding matrix. These cells acquire mobility by an epithelial-mesenchymal transition (EMT) that allows an epithelial cell to become mesenchymal [8]. The biological changes of EMT can include mutations on genes that are involved in epithelial growth factors, tissue hypoxia, metabolic and mechanical stress, and matrix composition. Mutations in EMT transcription factors could result in repressing epithelial genes and activating mesenchymal ones, or in epigenetic modifications that facilitate cancer cell invasion and migration. Once cells acquire the ability to invade new tissues, they adapt by proliferating in their new microenvironment.
One of the main strategies for cancer cells to thrive in new microenvironments and to promote cancer growth in their primary niche is to accumulate genetic and epigenetic modifications that are advantageous for metabolic rewiring. Metabolism in cancer cells may include changes in the use of glucose, amino acids, nitrogen, and alterations in metabolic gene regulation [9]. Among many nutrients, the most relevant ones are glucose and glutamine as they play a crucial role in carbon degradation, synthesis of macromolecules, ATP generation, nitrogen uptake, and nucleotide biosynthesis [10]. In the case of glucose, cancer cells have developed the “Warburg effect;” the increased utilization of glucose under aerobic conditions. This effect results from genetic and epigenetic changes that increase the transport and degradation of glucose, as well as in the deregulation of signaling pathways such as PI3K/Akt and the oncogenes KRAS proto-oncogene GTPase (
Finally, a hallmark of all cancer types is the ability to evade immune surveillance. The immune system uses cancer-immunoediting to regulate and eliminate cells that proliferate uncontrollably. Immunoediting is made up of three phases: elimination, equilibrium, and escape. Elimination of cancer cells is the ultimate effect of the immune surveillance of the innate and adaptive immune systems. There must be a recognition of tumor cells by innate immune cells, a maturation and migration of antigen-presenting cells, the generation of tumor-antigen-specific T-lymphocytes, the activation of cytotoxic mechanisms, and, finally, elimination of tumor cells [13]. For cancer immunoediting to be efficient, the immune system should be able to generate the genetic and epigenetic changes that are required to interact with tumor cells that undergo antigen remodeling and selection. Cancer cells with reduced immunogenicity result in the production of resistant variants with mutations that increase resistance to immune cytotoxicity. These tumor variants are characterized by genetic and epigenetic alterations that reduce tumor-antigen recognition, increase resistance to cell death, and induce immunological tolerance [14]. Furthermore, and in correlation with other hallmarks of cancer, cancer cells can suppress the cytotoxic components of the immune system through the secretion of immunosuppressive factors and inflammation. For example, cancer and stromal cells can secrete proinflammatory molecules, tumor-derived exosomes can suppress the function of immune cells, and metabolic rewiring and altered microbiome can result in negative regulation of the immune system [14]. In summary, the immune modulation observed in tumors is currently recognized as a key player during cancer initiation and progression, and as a promising field for therapeutic manipulation.
Importantly, a major disparity in the prevalence, incidence and mortality of colorectal cancer (CRC) between African Americans (AA) and Caucasian Americans (CA) exists. Differences in response to treatment is an established factor influencing the overall survival of CRC patients. Here, we will address tumor biology and the importance of inclusivity in research. Knowledge of the molecular differences in CRC arising in different populations is needed to drive new therapeutic strategies and help overcome treatment resistance mechanisms to reduce disparities observed for this disease in minority populations. Depicted in Figure 1 is an overview of those factors associated with cancer initiation, progression, and health disparity. Although we focus in this report on tumor biology, it is important to note that social determinants of health factor strongly into health disparity. Therefore, it is imperative that we not only understand tumor biology but are also able to address social determinates of health with respect to overall survival of all colon cancer patients.
Differences between AA and CA colon cancer patients at various levels of genomic expression and control; specifically, gene expression, DNA methylation, and chemotherapeutic response. Upstream factors are associated with and driven by social determinates of health. IND (investigational new drugs), SOC (standard of care), and NA (normal adjacent).
As it was mentioned in the introduction, cancer can arise from any cell in the human body that grows in an uncontrollable manner [1]. When classified by the location, or tissue, of origin, there about 200 different kinds of cancers. Nevertheless, when we focus on the aberrant gene expression of cancer and how it relates to the cellular composition, it can be concluded that there are 5 types of cancer: carcinoma, sarcoma, leukemia, lymphoma and myeloma, and brain and spinal cord [1].
Carcinomas can develop from the epithelial cells from the skin or the tissue lining of internal organs. Therefore, they could be further classified depending on the “skin layer” where they are localized, namely as adenocarcinomas, basal cell carcinomas, squamous carcinomas and transitional cell carcinomas. Another type of cancer—sarcoma—arises from connective tissue such as bone, cartilage, adipose tissue, muscles and vascular tissue (i.e., blood vessels). Leukemia, on the other hand, is characterized by developing specifically in white blood cells and its primary source, the bone marrow. The lymphomas and myelomas, develop from cells from the immune system, from locations such as the lymph nodes and the spleen. Lastly, cancers from the central nervous system, will be present in the brain and the spinal cord [1].
Carcinomas are the most common type of cancer, with 85% of the cancer cases in the United States, and include lung and colon cancer, which are number one and third in terms of incidence, respectively [1]. Sarcomas on the other hand, compose less than 1% of the cancer cases and most of the diagnosis are bone sarcomas [1]. Although leukemias are only the 3% of cancer cases in the United States, they are the most common type of cancer in children [1]. Cancers of the lymphatic system—lymphomas and myelomas—are 5% and 3% of the cancer cases, respectively. These cancers are particularly challenging to treat as they arise from abnormalities in the bone marrow, and they commonly require bone marrow transplantation [1]. Finally, brain and spinal tumors are 3% of the cancer cases in the USA and the most frequent subtype is the brain tumor from glial cells [1]. Taken together, it can be concluded that there are several cancer types and subtypes, based on the cellular composition of the cancer source. It is important to be noted, however, that many cancer types share aberrant gene expression that can cross over cancer types and subtypes. Therefore, we will address the shared genetic transgressions across the most common cancer types.
To address the observed abnormalities of gene expression across cancer types, we will start by describing the molecular basis for cancer progression. Mutations that lead to oncogene (stimulators of cell division) activation and tumor suppressor (regulators of cell cycle) dysregulation influence cancer initiation and progression. Such aberrant gene expression will, in turn, contribute to the hallmarks of cancer: unregulated growth and cell death. It is important to emphasize that the functional distinctions of mutations on the same gene from one cancer classification to another relies on the cellular differences and the distinct pathways that are deregulated in each cancer type.
Not surprisingly, most oncogenes and tumor suppressor genes are components of pathways that are involved in cell signaling. They are responsible for the regulation and generation of molecular signals, such as proteins, receptors, ligands, etc. For example, mutations in receptors of the tyrosine kinases RAS family, may act as oncogenes that are present in up to 80% of carcinomas [4]. Other signaling molecules that normally act as tumor suppressors, such as the TGFβ family, can lose regulatory function and commonly present as constitutively active receptors due to mutation [4]. An important example of aberrant gene expression in key pathways of cellular proliferation are those that are involved in DNA repair and cell division. A clear point of reference is the tumor suppressor gene
The extent of the contribution of a single gene to the development of different cancer types is best exemplified by the aberrant mutations in the
Taken together the hallmarks of cancer and overlapping aberrant alterations in gene expression across cancer types, it is appropriate to conclude that using a type of cancer as a model of study, could allow us to better understand the genetics of cancer as a whole. Thus, we have selected colon cancer to illustrate some of the general principles and molecular mechanisms of tumor progression due to aberrant gene expression. Considering the global prevalence of colon cancer, responsible of about 11% of the cancer deaths, along with its defined stepwise genetic hallmark timeline, this cancer type seems to be the perfect prototype to address cancer gene expression. In addition, colon cancer provides researchers with the opportunity to study the physical progression of a tumor in the human epithelium along with the molecular changes that result from aberrations at the gene expression level.
Colorectal cancer (CRC) is one of the most common cancers across the globe. It is estimated that the incidence of colon cancer will increase by 60% in several countries, positioning CRC as the second deadliest cancer type [15]. Up to 90% of CRC tumors arise from adenocarcinomas from the colon and rectum and up to 65% of the cases are sporadic (without a family history of CRC) [16]. Thus, the majority of CRC tumors progress from somatic and epigenetic alterations from modifiable risk factors such as metabolic comorbidities (e.g., obesity), diet, smoking, and alcohol consumption, among others [16]. It is important to highlight, however, that regardless of their inherited or somatic nature, several genetic factors and pathways have been identified in the pathogenesis of CRC.
In cases of hereditary CRC tumors, approximately 5% are classified as familial adenomatous polyposis (FAP) induced by alterations in the adenomatous polyposis coli (
Hence, either from hereditary factors or from genetic changes during the life span of the patient, CRC is determined by several genetic pathways. Although CRC tumors are considered heterogeneous at the molecular level, all tumors from the chromosomal instable pathway (CIN) have in common the accumulation of mutations after cell division cycles and loss of chromosomal stability [19]. This pathway is characterized by increased mutation rates, alterations in chromosome number, and rearrangement of chromosomes, which are detected by karyotyping and DNA analysis [19]. Some of the mechanisms by which CIN contributes to CRC tumorigenesis are mutations in key, cell cycle-related genes. These key genes include
Following CIN, the second most relevant pathway in CRC is microsatellite instability (MSI). These tumors are characterized by genetic damage of the mismatch repair (MMR) system and they usually present inhibition of the DNA polymerase, that in turn creates short-term insertion-deletion loops (IDL) that further enhance genetic instability [22]. MSI tumors are clinically identified by the abnormal production of the proteins of the DNA MMR system: MLH1, MSH2, MSH6, and PMS2; whose main functions are to repair single base pair mismatches during DNA synthesis and to maintain genomic stability after each cell replication cycle [22]. MSI mostly occurs in the proximal colon and its classification is used as a biomarker for prognosis and standard of care (immunotherapies) based on the 5 microsatellite markers: mononucleotides BAT25 and BAT26, and the dinucleotides D2S123, D5S346, and D17S250 [23]. Moreover, CRC tumors can be classified as MSI-high (MSI-H), those with >30% markers that exhibit genetic instability, MSI-low (MSI-L) for tumors with less than 30% markers with instability or, microsatellite stable (MSS) for tumors with no genetic stability and normal production of the MMR proteins [23]. Contrary to the CIN pathway, MSI tumors are for the most part somatic defects in the MMR genes by either mutational inactivation or by epigenetic silencing of CpG due to aberrant methylation patterns that result in the silencing of promoter genes, although hereditary mutations are frequently reported in
To finalize our genetic factors in the CRC section, we will address the CpG island methylator phenotype (CIMP) serrated pathway. Tumors classified as CIMP have a high number of hyper-methylated genes, with promoters that are silenced and can cause the downregulation of gene expression and protein production [23]. Approximately 35% of CRC cases are CIMP and they have common molecular alterations in other pathways such as the MSI subtype, the hypermethylation of the
To address the specifics of the tumor biology of CRC among African American patients, we would like to start by describing the concept of cancer disparities that are observed in the United States of America (USA). The National Institutes of Health considers the main racial/ethnic minority groups to be African Americans, American Indians and Alaska Natives, Native Hawaiians and Pacific Islanders, and Hispanic/Latinos [24]. These minority populations are heterogeneous, and we acknowledge that these categories are socially constructed; however, they serve as the official method for tracking cancer incidence, progression, outcomes, and all the other metrics by which cancer care and research is organized in the USA. Hence, this section will start by providing a summary of the cancer disparities that are observed among underrepresented CRC patients and it will continue by focusing on the biological factors that have been studied in African American patients.
There are disparities in the incidence and mortality rates of CRC among all the mentioned minority groups when compared to the average USA population, which is in the majority composed of Caucasian Americans (CA) [24]. For instance, in terms of incidence, it is 45.7 for African American (AA) patients, and 34.1 for Latinos per 100.000 patients. Similar trends are reported for mortality rates, with 19.0 for AA and 11.1 for Latinos, indicating that although progress has been made in the prevention and treatment of CRC in the USA, these patients face challenges that are population-specific [24]. Many factors contribute to this phenomenon, including socioeconomic status and access to healthcare, among others; nevertheless, there are unique biological features that contribute to the tumor biology of CRC in each racial/ethnic group. In the case of AA and Latinos, it is worth mentioning the disparities in the risk of metastasis due to the reduced prevalence of tumors that are localized and regional (normally cured by surgery or radiation) when compared to CA patients, underscoring the biological differences between these populations [25].
As we discussed previously, CRC results from a combination of the patients’ genetic profile (hereditary factors) as well as environmental and somatic changes that will modulate the tumor biology of the colon, such as diet, body mass index, tobacco and alcohol intake, etc. In addition to these contributors, research has highlighted tumor biology that has been associated with each population and their influence in the response to treatment. Studies from clinical trials have shown racial/ethnic disparities in survival rates of stage III CRC cancer even when patients received the same standard of care, greater toxicity in response to 5-fluorouracil (5-FU) therapy regimens, and unique pharmacogenetic variants in AA patients [26]. Also, the frequency of the MSI/MMR-deficient tumor subset, which is associated with better prognosis and serves as a biomarker for immunotherapies, appears to be reduced in AA when compared to CA patients (14 in CA vs. 7% in AA) [27].
Regarding the inherited, germline-associated syndromes in CRC, such as the familial adenomatous polyposis, AA seem to have a prevalence comparable to the other populations in the USA [28]. Despite that, previous investigations have identified unique somatic mutations in the 5-Hydroxytryptamine Receptor 1F (
microRNAs (miRNAs), powerful regulatory RNAs 18–24 nt in length, play a major role in oncology pathways. As miRNAs can potentially serve as biomarkers for CRC at several levels, understanding miRNA dysregulation is important in defining its effects on biomolecular pathways and developing possible therapeutic targets. This section will discuss miRNA expression patterns characteristic of CRC tumors, miRNAs identified as potential non-invasive biomarkers, their role in chemo-response, their contribution to racial health disparities, and their use as therapeutic targets.
miRNA dysregulation is a common component of many cancers, including in CRC. Among the hundreds of discovered miRNAs, the most relevant miRNAs unique to CRC tumors compared to healthy tissue, as well as their primary oncological function, is summarized in Table 1 (upregulated miRNAs) and Table 2 (downregulated miRNAs). Notably, available data from The Cancer Genome Atlas was used to provide a comparative analysis of miRNA expressed in colon tumors (N = 253) versus uninvolved normal tissues (N = 8). Of these, 39 upregulated and 54 downregulated miRNAs were implicated in colon cancer and, 9 of them were critical with a downstream impact on 461 genes associated with patient survival [85]. Among others, pathways affected by these miRNAs include Wnt signaling, p53, cell adhesion, cAMP signaling, stem cell pluripotency, MAPK, and HIF-1 [85]. In the pathway network of these miRNAs, five ‘hub’ genes (genes that have high connectivity to oncological pathways) were identified as mediating the function of these miRNAs:
[CRC tumor miRNA profile] summary of upregulated miRNAs (tumor vs. normal tissue) | ||
---|---|---|
Biological function | Upregulated miRNAs | Reference |
Promotes cell cycle/proliferation | 17-3p, 20a, 21, 26a, 31, 106a, 135a/b, 141, 200c, 301a, 598, 1273g-3p | [31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42] |
Promotes migration/invasion/metastasis | 20a, 21, 26a, 29a, 31, 135a/b, 155, 200c, 224, 301a, 494, 1273g-30 | [32, 33, 34, 35, 37, 39, 40, 42, 43, 44, 45, 46] |
Inhibits apoptosis | 17-3p, 31, 92a, 106a, 135a/b, 200c | [31, 35, 36, 37, 39, 47] |
Involved in drug sensitivity/resistance | 96, 155, 192/215 | [44, 48, 49] |
Hypoxia/ROS regulation | 210 | [50] |
Malignant transformation | 182/503 | [51] |
CRC stem cell tumorigenicity | 221 | [52] |
Ambiguous | 18a (both an oncomiR and Tumor Suppressor), 217 (inhibits proliferation/promotes apoptosis) | [53, 54] |
Upregulated miRNAs in CRC tumor tissue vs. normal tissue.
[CRC tumor miRNA profile] summary of downregulated miRNAs (tumor vs. normal tissue) | ||
---|---|---|
Biological function | Downregulated miRNAs | Reference |
Inhibits cell cycle/proliferation | 7, 18a-3p, 27b, 30a, 101, 125a/b, 126, 143/145, 144, 149, 155, 186-5p, 194, 205-5p, 216a-3p, 320a, 330, 374b, 375, 383, 455, 486, 511, 744, 1271, let-7 | [53, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79] |
Inhibits migration/invasion/metastasis | 7, 19b-1, 26b, 27b, 101, 125a/b, 126, 155, 186-5p, 205-5p, 320a, 328, 330, 374b, 455, 511, 744, 1271 | [55, 56, 58, 59, 60, 64, 65, 67, 69, 70, 71, 74, 76, 77, 78, 80, 81, 82] |
Promotes apoptosis | 7, 18a-3p, 30a, 101, 129, 143/145, 149, 155, 455, 511, 744, 1271, let-7 | [53, 55, 57, 59, 63, 64, 74, 76, 77, 78, 79, 83] |
Involved in drug sensitivity/resistance | 26b, 328, 1271 | [78, 81, 82, 84] |
Involved in angiogenesis | 375 | [72] |
Downregulated miRNAs in CRC tumor tissue vs. normal tissue.
The feasibility of using miRNAs as biomarkers stems from their general stability in blood, owing to their structure which resists RNAse-mediated degradation [88]. miRNAs that may serve as CRC non-invasive biomarkers are summarized in Table 3 [101]. Thus, exosomes-circulating miRNAs may have value as early, non-invasive CRC biomarkers [89]. For example, serum from CRC patients contained 69 miRNAs that were significantly upregulated compared to normal subjects. Additionally, cell culture media from five CRC cell lines demonstrated 52 upregulated miRNAs compared to culture media from normal colon epithelial cells. For both these
[Diagnostic biomarkers] summary of upregulated in serum/plasma (CRC vs. healthy patient) | ||
---|---|---|
Location of biomarker | miRNA | Reference |
Upregulated in serum (CRC patient vs. healthy control) | 21, 23a, 150, 181b/d, 223, 483-5p, 638, 1224-5p, 1229, 1246, 1268, 1290, 1308, 1915, let-7A | [89] |
Upregulated in serum (CRC patients vs. healthy control) | 18a, 24, 24-2, 29a, 122, 135a-5p, 139-3p, 139-5p, 203, 320a, 423-5p, 6826 | [86, 90, 91, 92, 93, 94, 95, 96, 97] |
Markers in plasma exosomes | 17-5p, 21, 92a-3p, 6803-5p | [98, 99, 100] |
Summary of miRNAs that have potential as non-invasive biomarkers.
Since miRNAs modulate drug targets directly or indirectly, response to standard of care (SOC) chemotherapeutic agents may be influenced by the dysregulation of select miRNAs. Indeed, expression of miRNAs is altered upon treatment of CRC cell lines with 5-fluorouracil (5-FU). Patients who did not respond well to fluoropyrimidine chemotherapy had higher plasma levels of miR-106, miR-484, and miR-130b [102]. Furthermore, higher miR-27B, miR-148A, and miR-326 levels were associated with decreased progression-free survival, whereas miR-326 was related to decreased overall survival [102]. Additionally, 5-FU reduces miR-200b, which lowers the levels of the protein tyrosine phosphatase, PTPN12, which, in turn, downregulates oncogenes, including
Lacking in our understanding, due to the absence of or limited use of AA samples in bench and clinical studies, is the role of miRNA in CRC racial health disparity in terms of cancer initiation and chemo-response. Microarray and qPCR analysis implicated miR-182, -152, -204, -222, and -202 when comparing AA and CA tumor samples [104]. Among these, miR-182 was the most significant—upregulated in AA vs. CA—in race tumor interactions.
The ability of miRNA to regulate expression of many downstream genes and the proficiency of biotechnology to synthesize oligonucleotides, promote and enable the use of these molecules as potential therapeutic agents. miR-34a, a central miRNA in the p53 stress pathway, is often lost in CRC and has been the hallmark of miRNA mimic therapy. In a phase 1 clinical trial, liposomal miR-34a mimics were shown to provide benefits against advanced solid tumors; however, these mimics were accompanied by many off-target-side-effects and adverse immune reactions [106]. Other strategies may include inhibiting oncogenic miRNA or more specific targeting of tumor miRNA replacement therapy. The challenge of miRNAs as therapeutic agents is a limited understanding of their targeted pathways in various tissues.
miRNAs have become vital as prognostic and therapeutic biomarkers/targets for cancer. miRNA dysregulation in CRC, along with their role in racial health disparities, is continually being explored. Identification and profiling of miRNAs in diverse patient population will result in the generation of personalized therapeutic targets which will allow for optimal patient care.
A major component of gene expression is DNA methylation. It is well documented that aberrant methylation patterns in CRC contribute to tumorigenesis and progression. This section will discuss dysregulated methylation patterns of CRC; specifically, pathways affected by aberrant methylation (hypo−/hypermethylation) and differential methylation of CRC tumors of African American patients.
In general, 10–40% of CRC tumor cells have a hypomethylated genome [107]. Most of this hypomethylation occurs in repetitive elements and influences the initiation of tumorigenesis [108].
In addition to hypomethylation, specific promoters involved in CRC can be hypermethylated. While hypermethylation of tumor suppressors is a normal part of aging, some methylation patterns describe preferential hypermethylation of tumor suppressors [112]. For example, the CpG-island methylator phenotype (CIMP) produces a subtype of CRC in which CpG islands of tumor suppressor genes become hypermethylated through an epigenetic instability pathway [112]. As proposed by Ehrlich and colleagues, the consequences of aberrant methylation include genomic instability, epigenetic inactivation of tumor suppressors, altered chromatin heterostructure interactions, and activation of oncogenic elements [107].
Specific CRC-relevant pathways are affected by methylation. A few are described here. In Wnt signaling, the
Aberrant methylation in CRC has been shown to stem from several sources. First, deregulation of relevant methylation enzymes like DNA methyltransferases (DMNT) can kickstart aberrant methylation. While DMNT is rarely mutated in CRC (unlike other cancers), the protein is overexpressed but not related to a specific aberrant methylation phenotype [119, 120].
Importantly, it was reported in one study that the CRC tumors of AA patients had 14.6-fold more hypermethylated regions and 25-fold more hypomethylated regions than CA in respect to tumor versus normal tissue [124]. In AA tumors,
In addition to mutations, dysregulation of gene expression through epigenetic alterations (i.e., methylation) impacts the initiation and progression of CRC. However, while global hypomethylation and local hypermethylation are prevalent, more specific patterns may need to be analyzed for therapeutic consideration. Beyond the comparisons of CRC tumors to normal tissue concerning methylation patterns, although limited in the scope of race and ethnicity, there are also marked differences between tumors originating from different racial groups. However, these findings may be instrumental in predicting tumor aggressiveness and responsiveness to standard of care and novel treatment modalities.
As we discussed in the introduction, evasion of immune surveillance is one of the hallmarks of cancer cells. Hence, we will discuss how genetic factors, tumor biology, and genetic regulators (miRNAs and DNA methylation patterns) intersect with the immune system in CRC in AA patients.
Colon tumors closely interact with immune cells that reside at the tumor site (microenvironment) and immune cells that are part of the systemic immune surveillance system. They both play a role in tumor progression, prognosis, and response to treatment in CRC [125]. Lymphocytes, cytotoxic CD8+ T cells to be precise, are one of the most efficient immune cells to perform surveillance, to limit the tumor progression in CRC and their filtration into tumors and are associated with better prognosis and outcome. The presence of high levels of CD8+ T cells in the center and invasive margins of colon tumors have been associated with improved patients’ survival when compared with patients with low infiltration of the same cell type [126]. These lymphocytes can ignite apoptosis in target cells by the secretion of (among others) the serine protease Granzyme B. Granzyme B+ T and Natural Killer (NK) cells are activated in response to the presence of neoantigens in the surface of cancer cells (recognized by antigen-presenting cells); especially from hypermutated tumors that are mostly classified as MSI due to their genetic instability and MMR deficiency [126]. In the context of AA CRC patients, however, it has been demonstrated that in MSI-H tumors, these patients presented lower infiltration of CD8+ T cells when compared to tumors from the same subtype from CA patients [127]. Furthermore, a study that investigated 250 CRC cases and compared MSS tumors from AA and CA patients found that tumors from AA patients had lower numbers of GRANZYME B+ lymphocytes, suggesting that CRC in AA is characterized by impaired immune surveillance and lower cytotoxicity regardless of tumor type [128].
These disparities in the immunological profile of CRC tumors in AA patients also influence the access of these patients to the immunotherapies available for CRC cancer. For example, when cytotoxic T cells are activated by tumoral antigens they will induce memory T cells that are characterized by the expression of the programmed cell death protein 1 (PD-1) receptor on their surface that serves as a negative feedback loop for the inactivation of these lymphocytes and prevents auto-immunity [129]. This receptor will interact with the PD-1 ligand that can be on the surface of cancer cells as a tumoral strategy of immune-surveillance evasion, and it is the target of the PD-1/PD-L1 antibody therapy that blocks this interaction and releases CD8+ T cells from the negative effects of the PD-L1 ligand. Not surprisingly, and as we mentioned in the tumor biology section, the MSI tumor classification is a biomarker for access to this immunotherapy based on the direct correlation of hypermutation in cancer cells, expression of neo-antigens and PD-L1 ligands, response to the anti-PD-1 antibody therapy, and positive outcome [130].
Remarkably, a research study that compared the gene expression of CRC tumors from AA and CA patients confirmed that tumors from AA had a lower expression of the
The push for research in CRC racial health disparity and inclusivity in clinical trials represents a major step forward in personalized medicine and optimizing health outcomes for a diverse patient population. To continue the acceleration of current progress, new future directions in the analysis and development of novel
Not only will these multidimensional analyses aid the progress of CRC research, but so will the development of tools that seek to make racial health disparity research more accessible. Social determinants of health are important components of health disparity; however, collective studies have demonstrated that research observations support differences in the distribution and pattern of driver mutations in diseases such as colon cancer that present more in AA patients as compared to CA patients. The etiologic basis for differences between race groups, such as higher rates of
Multi-omics assessment combined with accessible tools, the exploration of CRC gene expression, and overall biology will make possible an understanding that can be therapeutically targeted for the maximum benefit of the patient. Discovery and validation methods are provided in Figure 2. Given the multidimensionality of CRC, it is scarcely sustainable to maintain blanket standards of care that have abhorrent side effects with a sizeable chance of failure. Ideally, sampling a patient’s tumor and having a pipeline of treatments optimized for their genetic, epigenetic, and metabolomic profile will be the future of cancer treatment. In a diverse patient population with racial health disparities among other socioeconomic obstacles, research aimed at unpacking these complexities is vital for getting closer to the goal of a personalized approach for healing patients.
Assessment methods to address differences in response to treatment.
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. 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Most smart home systems are controlled by smartphones and microcontrollers. A smartphone application is used to control and monitor home functions using wireless communication techniques. We explore the concept of smart home with the integration of IoT services and cloud computing to it, by embedding intelligence into sensors and actuators, networking of smart things using the corresponding technology, facilitating interactions with smart things using cloud computing for easy access in different locations, increasing computation power, storage space and improving data exchange efficiency. In this chapter we present a composition of three components to build a robust approach of an advanced smart home concept and implementation.",book:{id:"7602",slug:"internet-of-things-iot-for-automated-and-smart-applications",title:"Internet of Things (IoT) for Automated and Smart Applications",fullTitle:"Internet of Things (IoT) for Automated and Smart Applications"},signatures:"Menachem Domb",authors:[{id:"222778",title:"Prof.",name:"Menachem",middleName:null,surname:"Domb",slug:"menachem-domb",fullName:"Menachem Domb"}]},{id:"12044",doi:"10.5772/10167",title:"Introduction to Packet Scheduling Algorithms for Communication Networks",slug:"introduction-to-packet-scheduling-algorithms-for-communication-networks-",totalDownloads:5468,totalCrossrefCites:18,totalDimensionsCites:19,abstract:null,book:{id:"3663",slug:"communications-and-networking",title:"Communications and Networking",fullTitle:"Communications and Networking"},signatures:"Tsung-Yu Tsai, Yao-Liang Chung and Zsehong Tsai",authors:null},{id:"65738",doi:"10.5772/intechopen.84338",title:"Privacy of IoT-Enabled Smart Home Systems",slug:"privacy-of-iot-enabled-smart-home-systems",totalDownloads:1545,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"Digital ecosystems are going through a period of change due to the advancement in technologies such as Internet of Things (IoT) as well as proliferation of less expensive hardware sensors. Through this chapter, we present current emerging trends in IoT in different industry sectors as well as discuss the key privacy challenges impeding the growth of IoT to reach its potential in the smart home context. The majority of the existing literature on IoT smart home platforms focuses on functionalities provided by smarter connected devices; however, it does not address the concerns from a consumer’s viewpoint. Thus, the key questions are: What are the privacy concerns related to IoT, particularly from a “smart home device” consumer viewpoint? What are the existing remedial approaches for privacy management? This chapter proposes a framework to assist smart home user and IoT device manufacturer to make informed privacy management decisions. The findings of this research intend to help practitioners and researchers interested in the privacy of IoT-enabled smart systems.",book:{id:"7602",slug:"internet-of-things-iot-for-automated-and-smart-applications",title:"Internet of Things (IoT) for Automated and Smart Applications",fullTitle:"Internet of Things (IoT) for Automated and Smart Applications"},signatures:"Avirup Dasgupta, Asif Qumer Gill and Farookh Hussain",authors:[{id:"277383",title:"Mr.",name:"Avirup",middleName:null,surname:"Dasgupta",slug:"avirup-dasgupta",fullName:"Avirup Dasgupta"},{id:"278569",title:"Dr.",name:"Asif",middleName:null,surname:"Gill",slug:"asif-gill",fullName:"Asif Gill"},{id:"278570",title:"Dr.",name:"Farookh",middleName:null,surname:"Hussain",slug:"farookh-hussain",fullName:"Farookh Hussain"}]},{id:"67035",doi:"10.5772/intechopen.86014",title:"IOT Service Utilisation in Healthcare",slug:"iot-service-utilisation-in-healthcare",totalDownloads:1892,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Utilising the new trend technologies in healthcare sector could offer alternative ways in managing the patients’ health records and also improve the healthcare quality. As such, this chapter provides an overview of utilising the Internet of Things (IoT) technology in healthcare sector as an emerging research and practical trend nowadays. The main benefits and advantages have been discussed in this chapter. On the other hand, it has been found that most of the hospitals in different countries are still facing many issues regarding their health information exchange. Recently, various studies in the area of healthcare information system mentioned that the fragmentations of the health information are one of the most important challenges with the distribution of patient information records. Therefore, in this chapter, we gave an in detail overview regarding the current issues facing the health sector in line with the IoT technologies. Additionally, a full description of advantages and disadvantages has been highlighted for using IoT in healthcare that can be considered as solutions for the mentioned issues.",book:{id:"7602",slug:"internet-of-things-iot-for-automated-and-smart-applications",title:"Internet of Things (IoT) for Automated and Smart Applications",fullTitle:"Internet of Things (IoT) for Automated and Smart Applications"},signatures:"Mohammed Dauwed and Ahmed Meri",authors:[{id:"248015",title:"Dr.",name:"Ahmed",middleName:null,surname:"Meri",slug:"ahmed-meri",fullName:"Ahmed Meri"},{id:"276426",title:"Dr.",name:"Mohammed",middleName:null,surname:"Ahmed Dauwed",slug:"mohammed-ahmed-dauwed",fullName:"Mohammed Ahmed Dauwed"}]},{id:"60331",doi:"10.5772/intechopen.75137",title:"IoT Standardization: The Road Ahead",slug:"iot-standardization-the-road-ahead",totalDownloads:1863,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"The Internet of Things (IoT) is an emerging area of the modern technology which impacts use cases across governance, education, business, manufacturing, entertainment, transportation, infrastructures, health care, and so on. Creating a generalized framework for the IoT with heterogeneous devices and technology support requires interoperability across products, applications, and services that preclude vendor lock-in. Global standardization of the IoT is the only solution to this. Though standardization efforts in the IoT are not new with many national and international standard bodies working today, there are many open areas to debate and standardize—like reconciling country-specific efforts, empowering local solutions, etc. This chapter brings a holistic view of the existing IoT standards, discusses their interlinking, and enumerates the pain points with possible solutions. 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The chapter describes the design of the system, its hardware components, software implementation, security solutions, communication, the collecting and monitoring of processed data, as well as the quantification of costs for the production and deployment of this system. The proposed system secures a house by detecting an intruder in the building, triggering an alarm and capturing it all with camera images, and then sending data to the owner’s smart mobile phone. 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Additionally, a full description of advantages and disadvantages has been highlighted for using IoT in healthcare that can be considered as solutions for the mentioned issues.",book:{id:"7602",slug:"internet-of-things-iot-for-automated-and-smart-applications",title:"Internet of Things (IoT) for Automated and Smart Applications",fullTitle:"Internet of Things (IoT) for Automated and Smart Applications"},signatures:"Mohammed Dauwed and Ahmed Meri",authors:[{id:"248015",title:"Dr.",name:"Ahmed",middleName:null,surname:"Meri",slug:"ahmed-meri",fullName:"Ahmed Meri"},{id:"276426",title:"Dr.",name:"Mohammed",middleName:null,surname:"Ahmed Dauwed",slug:"mohammed-ahmed-dauwed",fullName:"Mohammed Ahmed Dauwed"}]},{id:"75630",title:"Internet of Things Security and Privacy",slug:"internet-of-things-security-and-privacy",totalDownloads:437,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The Internet of Things is becoming more and more popular with time. The extremely low cost of sensors is putting the growth of the Internet of Things on steroids. Many industries such as healthcare, construction, agriculture, and transportation are increasingly leveraging this technology. However, security and privacy are two big concerns when it comes to the future of the Internet of Things. Since most of these “things” that are connected to the Internet are simple devices with limited hardware capabilities, it is nearly impossible to harden them via traditional resource-heavy defenses. In this chapter, we discuss the importance of securing the Internet of Things networks, layout the challenges of the Internet of Things security, and briefly discuss potential solutions in the literature.",book:{id:"10419",slug:"internet-of-things",title:"Internet of Things",fullTitle:"Internet of Things"},signatures:"Ahmad J. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. 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He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"435274",title:null,name:"Muhammad",middleName:null,surname:"Shahid Khan",slug:"muhammad-shahid-khan",fullName:"Muhammad Shahid Khan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Islamia University of Bahawalpur",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"11",type:"subseries",title:"Cell Physiology",keywords:"Neurodevelopment and Neurodevelopmental Disease, Free Radicals, Tumor Metastasis, Antioxidants, Essential Fatty Acids, Melatonin, Lipid Peroxidation Products and Aging Physiology",scope:"\r\n\tThe integration of tissues and organs throughout the mammalian body, as well as the expression, structure, and function of molecular and cellular components, is essential for modern physiology. The following concerns will be addressed in this Cell Physiology subject, which will consider all organ systems (e.g., brain, heart, lung, liver; gut, kidney, eye) and their interactions: (1) Neurodevelopment and Neurodevelopmental Disease (2) Free Radicals (3) Tumor Metastasis (4) Antioxidants (5) Essential Fatty Acids (6) Melatonin and (7) Lipid Peroxidation Products and Aging Physiology.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11407,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null,series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević",profilePictureURL:"https://mts.intechopen.com/storage/users/186048/images/5818_n.jpg",institutionString:null,institution:{name:"University of Osijek",institutionURL:null,country:{name:"Croatia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria",profilePictureURL:"https://mts.intechopen.com/storage/users/79615/images/system/79615.png",institutionString:null,institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}},{id:"84459",title:"Prof.",name:"Valerie",middleName:null,surname:"Chappe",slug:"valerie-chappe",fullName:"Valerie Chappe",profilePictureURL:"https://mts.intechopen.com/storage/users/84459/images/system/84459.jpg",institutionString:null,institution:{name:"Dalhousie University",institutionURL:null,country:{name:"Canada"}}}]},onlineFirstChapters:{},publishedBooks:{},testimonialsList:[{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}}]},submityourwork:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/48234",hash:"",query:{},params:{id:"48234"},fullPath:"/chapters/48234",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()