miRNAs in liver cancer development.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\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:"1840",leadTitle:null,fullTitle:"The Cardiovascular System - Physiology, Diagnostics and Clinical Implications",title:"The Cardiovascular System",subtitle:"Physiology, Diagnostics and Clinical Implications",reviewType:"peer-reviewed",abstract:"The cardiovascular system includes the heart located centrally in the thorax and the vessels of the body which carry blood. 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\r\n\tAlthough the diagnosis and overall survival of patients with various cardiac diseases have improved in the last years, there still remains a significant proportion of patients with unfavorable prognoses. The evaluation of these patients necessitates effective imaging techniques in both diagnosis and long-term follow-up. Even though Cardiac Magnetic Resonance imaging is currently the imaging modality of choice for tissue characterization, advanced echocardiography represents a modern alternative. Speckle tracking echocardiography can be used to assess myocardial deformation at both segmental and global levels. Since distinct myocardial pathologies affect deformation differently, information about the underlying tissue can be offered by strain imaging. Echocardiography advances also show promising results in the improvement of diagnostic accuracy, management, and follow-up and a major advantage of echocardiography over other imaging modalities is the ability to use it in real-time, in the cardiac catheterization laboratory, allowing for the performance of imaging immediately before, during, and after interventional procedures. Furthermore, the prevalence of adult congenital heart disease continues to grow due to advances in surgical and diagnostic techniques. Echocardiography has proven to be a useful tool in the diagnosis and follow-up of these patients, both after percutaneous and surgical procedures, and its utility has expanded significantly due to the development of better technology. In addition, stress echocardiography could be useful in the evaluation of several cardiac diseases and should be preferred over other imaging modalities due to the lower cost, wider availability, and radiation-free nature.
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art novel imaging techniques by focusing on the most important evidence-based developments in this area.
miRNAs are small noncoding RNAs ~20–25 nt long, which are involved in epigenetic regulation of gene expression. miRNAs were firstly discovered in 1993, when research groups led by Victor Ambros and Gary Ruvkun published two side-by-side papers in the journal Cell, describing the regulatory effects of tiny RNA discovered in Caenorhabditis elegans. Years later the term “microRNA” (miRNA, miR) was introduced [1]. Nowadays, more than 2600 miRNAs have been predicted to be encoded by the human genome, with the ability to modulate more than 15,000 genes [2]. Being small and noncoding RNAs, they have a huge and significant function in gene regulation and cancer development. Liver cancer, although not being at the top of most common cancers, remains among cancers with high mortality. Hepatocellular carcinoma (HCC) accounts for approximately 80% of all liver cancers and is a main cause of cancer mortality [3]. Hereinafter, when using the term liver cancer, it is meant to indicate hepatocellular carcinoma. The most obvious and significant reason for this high mortality rate in HCC patients is the late diagnosis of HCC. Against this background, every aspect of molecular pathogenesis becomes a valuable detail, which may aid in understanding HCC development. Some of the main miRNAs involved in the development of liver cancer will be discussed further. Changes in their expression levels were detected in comparable conditions: mostly in human liver tissue samples or human blood samples (plasma or serum) by qRT-PCR.
Despite the simple structure of a mature miRNA molecule—single-stranded RNA molecule of 20–25 nt—its biogenesis, like almost any process relating to nucleic acids, is multistage and multifactorial: It takes place both in the nucleus and in the cell cytoplasm, involves protein complexes for processing (miRNA maturation), may be performed
miRNA processing may occur post- or co-transcriptionally [4]. miRNA biogenesis starts in the nucleus and requires RNA polymerase II/III; Drosha (an RNase III-like enzyme) with its cofactor, the RNA binding protein DGCR8 (DiGeorge Syndrome Critical Region 8), forms a microprocessor complex and functions in the nucleus, an exportin (frequently Exportin5 in the canonical pathway and Exportin1 in the non-canonical pathway) functioning as the transporter to the cytoplasm. Dicer, another RNase III-like endonuclease, RISC (RNA-induced silencing complex) functioning in the cytoplasm with Argonaute (AGO) as a core component. miRNA biogenesis starts with the processing of RNA polymerase II/III and forming pri-miRNAs, which are 5′ capped and 3′ polyadenylated, approximately several kilobases [5, 6]. In the canonical pathway, pri-miRNAs then are processed in the microprocessor complex of Drosha and DGCR8. The resulting ∼70 nucleotide RNAs with 2 nt 3′ overhang are known as precursor (pre-) miRNAs, which fold into mini-helical structures [7]. Pre-miRNAs are transported from the nucleus to the cytoplasm with Exportin 5/RanGTP complex, where they undergo processing with Dicer, which recognizes the pre-miRNA hairpin and cuts it at the loop end, resulting in the removal of the terminal loop and creating a ∼22 nt RNA duplex [8]. The final step of the miRNA biogenesis is processing the duplex miRNA into mature single-stranded miRNA by loading it onto an Argonaute (Ago) protein, which is the core protein in this final effector complex—RNA-induced silencing complex (RISC). The mature miRNA may be derived from both the 5’ and 3’ arms of the precursor duplex and are called the miRNA-5p and -3p, respectively [9].
As for regulation of miRNA expression with some miRNAs having their own promotors and some being regulated by other gene promotors, besides methylation, different endogenous factors, and hypoxia, different transcription factors (TF) also participate in miRNAs expression regulation and this is a double-edged process: TFs influence miRNA expression and miRNAs may repress TF expression [7, 10]. miRNA, TFs, and target genes form a complex relationship known as feedback loops (FBLs) and feed-forward loops (FFLs) [11]. Typically, FBLs occur when a TF activates or represses a miRNA, which in turn represses the TF; the miRNA and TF each regulate independent sets of TGs. FFLs are those where a regulator, such as a TF, controls the expression of a specific TG both directly, through promoting or enhancing its transcription, and indirectly, through another regulator, such as an miRNA that also regulates the TG [12].
mRNA and miRNA interaction implies binding of the last to the 3′ untranslated region (3′ UTR) of mRNA through base-pairing of the seed region of target mRNA, mainly at position 2–7 from the 5′ end of the miRNA; beyond the seed region, the binding between the whole mature miRNA sequence and the target mRNA is not perfectly complementary [13]. However, the interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, has also been reported. In general, there is no direct correlation between miRNA and target mRNA expression levels. Multiple miRNAs can regulate a single gene/mRNA, and some miRNAs can target many mRNAs (up to more than 100 mRNAs) and from 1 to 2% of human transcripts interact with nine or more miRNAs, thus displaying sponge-like activity [14]. Furthermore, miRNAs have been shown to activate gene expression under certain conditions [5]. Along with mRNAs differing in their miRNA-binding capacity, binding activity of some highly expressed miRNAs may be weakened by either a high target-to-miRNA ratio or the relocation of this miRNA to the nucleus. Some miRNAs might be expressed at relatively low levels and interact with many mRNAs and, oppositely, some miRNAs might be expressed at a very high level and interact with only a few mRNAs [15].
Considering all of the above, it makes identifying the specific miRNA-target gene or transcription factor-target gene interactions difficult, and possibly unwarranted [12].
Apparently, miRNAs are involved in all processes underlying normal liver functioning, so main pathologic processes, such as nonalcoholic fatty liver disease (NAFLD), fibrosis at the background of various diseases, and cancer are associated with significant changes in miRNA expression profiles, although these changes are not always associated with target mRNA expression changes and the mechanism of miRNA participation in these processes is not clear. A significant role of some miRNAs was shown for main liver functions such as lipid metabolism and all the steps of glucose metabolism, including lipogenesis.
Pivotal role of miR-34a in PPARα (the peroxisome proliferator-activated receptor alpha) pathway, which is a direct target of miR-34a and a master regulator of lipid metabolism, was shown in cultured cells transfected with miR-34a inhibitor and simultaneously consequences of miR-34a inhibition were shown in C57BL/6 mice injected with the miR-34a inhibitor [16]. The upregulation of miR-34a resulted in the downregulation of hepatic PPARα and SIRT1 (silent mating type information regulation 2 homolog 1), silencing miR-34a led to an initially increased expression of PPARα, SIRT1, and PPARα’s downstream genes, and activation of the central metabolic sensor AMPK was also increased. In the mouse model, the miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis, which is assumed to be regular as far as its level was significantly upregulated in liver tissues of high-fat diet-fed mice [17].
miR-122 is among those playing a crucial role in lipid metabolism in the liver: miR-122 expression in mice liver was increased by free fatty acids (FFAs)
Among other miRNAs, possibly acting as modulators of lipid and cholesterol levels in the maintenance of cholesterol and fatty acid metabolism, are miR-33, miR-103, miR-104, and miR-307 [22, 23]. Obviously, some miRNAs may be involved in both lipid and glucose metabolisms, as far as one miRNA may have multiple mRNA targets. One of these miRNAs is miR-33a and miR-33b, intronic miRNAs located within the sterol regulatory element-binding protein (SREBP) genes, working in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis. miR33b also cooperates with SREBP1, having an impact on key regulatory enzymes of hepatic gluconeogenesis glucose metabolism—phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC). Overexpression of miR-33b in human hepatic cells leads to a significant reduction of glucose production
miR-206 was shown as a potent lipid and glucose production inhibitor by simultaneously facilitating insulin signaling and impairing hepatic lipogenesis due to promoting phosphorylation of INSR (insulin receptor) and impaired hepatic lipogenesis by inhibiting Srebp1 (sterol regulatory element-binding transcription factor 1) transcription and inhibition of PTPN1 (protein tyrosine phosphatase, non-receptor type 1)
miR-103 and miR-107 were the first two miRNAs shown to regulate insulin sensitivity in liver and adipose tissue in mice: Their overexpression in these mouse models led to downregulation of caveolin-1 expression, a component of caveolae lipid raft required for insulin receptor signaling. miR-802 was also shown to be involved in the regulation of insulin sensitivity and glucose transport: elevated miR-802 decreased expression of HNF1β while increasing expression of the insulin suppressors, SOCS1 and SOCS3. Increased expression of both SOCS1 and SOCS2, in turn, desensitizes insulin signaling, resulting in increased hepatic glucose production in these mouse models [26]. It is worth noting that miR-23a was first reported as a regulator of gluconeogenesis through direct binding at the 3’-UTRs of both G6Pase and PGC-1α mRNAs, and later its expression was found to be elevated in hepatocytes of hepatocellular carcinoma mice where gluconeogenesis is attenuated [27].
In general, when discussing miRNA functions and interactions, it should be noted, besides its elusive relations with mRNA, that they are not limited to mRNA and involve other RNAs as well, that may influence its activity and function, for example, circRNAs have been validated as microRNA (miRNA) sponges, which have complementary sequences binding to their target miRNAs, thereby inhibiting the function of those miRNAs and abolishing the inhibition of target gene expression [27]. Circ-0000092 with such miRNA sponging activity and miR-338-3p as a target miRNA was shown to be elevated in HCC tissue (40 patients, RT-qPCR, GAPDH) and cell lines, while miR-338-3p was shown to be decreased (40 patients, RT-qPCR, U6 as an internal control) [28]. Simultaneously, miRNA-338-3p target, HN1, shown to be overexpressed by Liu et al. in liver cancer and known to be involved in metastasis and invasion development in breast and prostate cancer partly due to negative impact on the b-catenin/E-cadherin interaction, was shown to be elevated along with circ-0000092 [29]. These data along with the effects of delivery of a series of mimic, inhibitor, or siRNA plasmids into HCC cells on cell proliferation, migration, invasion, and angiogenesis
It is evident that most of the processes taking place in the liver in normal condition require different miRNAs and assumably healthy hepatocyte should have its “normal” miRNA profile with wide ranges, which make it possible to suggest—there are strong pieces of evidence that will be discussed further—those different pathologic processes, forming the diseases, are accompanied with different changes in miRNA expression levels. With regard to hepatocellular carcinoma, it could be speculated that in the very initial stages, particularly at preclinical stages when it is favorable for cancer background but still no clinical manifestation of cancer, liver cancer may have different miRNA expression profiles within the same cancer type. Further will be discussed the liver cancer development and partly the background of viral hepatitis B, viral hepatitis C, nonalcoholic fatty liver disease (NAFLD), and alcohol-related liver disease (ARLD).
miRNAs along with other nucleic acids have a significant impact on cancer development, where they may have both the role of cancer promotion and cancer suppression; therefore, miRNAs with increased expression in tumors are thought to function as oncogenes and are termed as oncomirs. On the contrary, miRNAs with decreased expression in cancer cells are considered tumor suppressor genes, presumably preventing tumor development by negatively inhibiting oncogenes and/or genes that control cell differentiation or apoptosis [32]. miRNAs are known to be involved in most signaling pathways, and in the liver cancer development, the same signaling pathways are involved, like in most other cancer types, such as TGF-β, Wnt/B-catenin, Hh, Notch, EGF, HGF, VEFG, JAK/STAT, Hippo, and HIF, which lead to uncontrolled cell division and metastasis [32].
Main miRNAs, involved in TGF-β regulation, are miR-200, miR-21, miR-211, miR-17/92, miR-106b/25, and miR-182 [33]. miR-200 and miR-21 are one of the main players among noncoding RNAs in interaction with TGF-β signaling in the process of EMT. miR-200 forming a double-negative feedback loop with ZEB factors (zinc finger E-box-binding homeobox) plays a significant role in EMT (epithelial-mesenchymal transition): miR-200 is downregulated because of reversible DNA methylation of the miR-200 loci as a result of prolonged autocrine TGF-β signaling, driving a sustained ZEB expression, and thus maintaining a stable mesenchymal phenotype. miR-200 is known to interact with both ZEB factors—(ZEB1; also known as deltaEF1) and SIP1 (also known as ZEB2) [34]. miR-200a is responsible for significant inhibition of cell proliferation and colony formation rate in HCCLM3 and HepG2 cell lines, while knocking out miR-200a restores the rate of proliferation and colony formation of cancer cells [35]. miRNA expression levels of miR-200 family tend to be decreased in individuals with liver cancer (plasma and tissue), compared with healthy individuals, and have a prognostic value for patients with HCC: microRNA-200a and miR-200c were independent prognostic factors for hepatocellular carcinoma and induced cell cycle arrest by targeting CDK6 or MAD2L1, respectively [36]. Opposite to miR-200 family, expression of miR-21 is induced in response to TGF-β signaling and is associated with tumor invasion and chemoresistance
Members of the miR-17-92 and the miR-106b-25 clusters have been implicated in the progression of liver fibrosis through the influence on the expression of TGF-β receptor II (TGF-βRII), having opposite effects on this expression. miR-19b has been shown to play an inhibitory role in hepatic stem cell-mediated fibrogenesis and to be decreased in fibrotic rats and human livers. Overexpression of miR-19b inhibited the expression of TGF-βRII, which in turn inhibited SMAD3 expression and, as a result, reduced type-1 collagen production. Unlike miR-19b, miR-93 and miR-106b were observed to be consistently upregulated during the development of cirrhosis, and miR-106b along with miR-181was shown to have a diagnostic value for liver cirrhosis irrespective of the etiology [40].
miR-211, which is known to be involved in TGF-β interaction in prostate cancer cells, was shown to be involved in WNT-β signaling regulation via SATB2. In prostate cancer cells, increased expression of miR-211 inhibited expression of TGF-β1, TGF-β2, smad2, smad3, phosphorylated smad2, and smad3, and stem cell markers and
MiR-125b is known to interact with the Hh pathway, which is a well-known factor regulating liver reconstitution. miR-125b, produced by CP-MSCs (chorionic platelet-derived mesenchymal stem cells), attenuates Hh activation partly due to Smo expression inhibition and the consequence of this regulation is the promotion of the regression of fibrosis, contributing to liver regeneration [42]. It was demonstrated that another target of miR-125b in HCC cells is LIN28B, and simultaneously miR-125b may increase p21Cip1/Waf1 expression and arrest cell cycle at G₁ to S transition, which may contribute to suppression of HCC cell migration, invasion, and growth
miRNA-199a-3p, being one of the putative therapeutic tools in liver cancer, may perform its anticancer effect through involvement in NOTCH signaling. miRNA-199a-3p is downregulated in liver cancer tissues and most liver cancer cell lines; in liver cancer cell lines (MHCC97H, Hep3B, SMMC-7721, Huh7, and HepG2), its expression was significantly lower than in normal liver cell lines; simultaneously, mRNA YAP1 expression was significantly higher than in normal liver cell lines. It was shown that miRNA-199a-3p targets YAP1, downregulates Jagged1, and suppresses the Notch signaling, which results in HCC cell proliferation inhibition and apoptosis promotion [46]. In a mouse model with induced HCC treatment with miRNA-199a-3p showed regression of hepatocellular carcinoma with the restoration of normal architecture on histopathological examination of liver specimens [47].
In liver cancer, HGF, ERBB3, and NF-κB form a positive feedback loop: higher expression of ERBB3 makes liver cancer cells more sensitive to HGF stimulation; moreover, HGF enhances ERBB3 expression by NF-κB transcriptional activity. miR-17-5p and miR-20a-5p in liver cancer cell lines and mice xenograft models were shown to suppress liver cancer cell proliferation after hepatectomy
Taking into account the ambiguous relation between miRNA and mRNA expression levels and other factors, including circRNAs and proteins, associated with miRNA biogenesis and those involved in miRNA and mRNA interactions, prediction of changes in miRNA expression levels in any cancer, including liver cancer, becomes not that obvious task.
Along with changes on the genetic level, metabolic changes accompany cancer development in order to provide cells functioning in changing conditions, mainly hypoxia and glucose insufficiency due to intensive cell proliferation and clonal expansion and lagging in blood vessel formation. One of the main such metabolic reorganizations is Warburg effect, firstly reported in rat liver carcinoma in the 1920s and defined as an increase in the rate of glucose uptake and preferential production of lactate even in the presence of oxygen [56]. Main miRNAs, which are involved in Warburg effect realization in HCC cells, are miR-1, miR-122, and miR-338-3p [57]. The expression of the miR-1 targets G6PD and is mediated by NRF2, which, besides activating the transcription of genes encoding glycolytic enzymes, inhibits the conversion of pyruvate to acetyl-CoA by directly activating pyruvate dehydrogenase kinase 1 (PDK1) and leads to inhibition of tricarboxylic acid (TCA) cycle, promoting Warburg effect [58]. At the background of these interactions, it may appear to be regular that a higher expression of miR-1 showed a significant positive prognostic meaning for patients with HCC: Individuals with higher miR-1 serum levels showed longer OS than those with lower miR-1 serum concentrations (195 sera of HCC patients and 54 patients with liver cirrhosis; HR 0.451, 95% CI 0.228–0.856, P = 0.015). At the same time, serum miR-1 and miR-122 concentrations did not differ significantly between patients with HCC and liver cirrhosis [58].
miR-122 is another element of the processes that are assumed to restrain Warburg effect promotion, as far as among its main targets are Agpat 1 and Dgat 1 mRNAs, involved in triglyceride synthesis. One of the most important direct targets of miR-122 in HCC cells is PKM2, which is the most abundant pyruvate kinase iso-enzyme in liver tumors and a co-activator of several transcription factors, such as HIF-1α, β-catenin/c-Myc, NF-κB, and STAT3. Once in the nucleus, PKM2 can promote the transcription of target genes, such as HIF-1α targeted expression of GLUTs, PKM2, LDH-A, and VEGF-A, leading to the promotion of growth, positive feedback regulated glycolysis, and angiogenesis in cancer cells [59], and all these allow miR-122 to promote a decrease in lactate production and increase in oxygen consumption, thus reversing oxygen-independent glycolytic metabolism. Along with this, Yang G. et al. showed that miR-122 is downregulated in tissue samples from patients with HCC and also participates in ADAM17 regulation, which makes upregulation of miR-122 to inhibit proliferation of HCC cells
miR-338-3p has the same impact on Warburg effect in cancer liver cells such as miR-1 and miR-122, inhibiting it through decreasing expression of liver and red blood cell pyruvate kinase isoform (PKLR). miR-338-3p may be inactivated in HCC due to upregulation of circMAT2B, sequestering miR-338-3p due to its sponging activity, and disabling the regulation of its target gene PKM2 leading to increased proliferation, invasion, spheroid formation, and organoid dimensions, especially in hypoxic conditions [59]. Expression of miR-338-3p in tissue samples from patients with HCC was also shown to be decreased [33].
miR-23 was shown to be involved in gluconeogenesis regulation in liver cancer developed in the mouse model. Reduction in serum glucose in tumor-bearing mice correlated with a reduction in the expressions of G6pc, Pepck, and Fbp1 encoding the key gluconeogenic enzymes glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, fructose-1,6-phosphatase, respectively, and the transcription factor Pgc-1α along with upregulation of miR-23a expression. mRNA levels of these genes were reduced to ≈80% in the majority of primary human HCC tissue samples compared with matching peritumoral liver samples and miR-23a was also upregulated in human liver cancer samples. Moreover, PGC-1α and G6PC expression negatively correlated with miR-23a expression in human HCCs [63]. miR-23a has a significant diagnostic value as far as it may distinguish cirrhotic liver samples from cancer liver samples, being higher in the HCC group than cirrhotic. miR-23a was significantly higher in HCC patients with focal lesion size equal or more than 5 cm, patients with multiple focal lesions, and Okuda stage III. At cutoff value ≥ 210, miR-23a showed accuracy of 79.3% to diagnose HCC patients with sensitivity of 89.47% and specificity of about 64.91% ((57 patients with HCC, 57 patients with liver cirrhosis (LC), and 57 healthy subjects as control group) and serum alpha-fetoprotein at cut off level ≥ 200 ng/mL had 73.68% sensitivity and 52.63% specificity for diagnosis of HCC [64].
Pathological states in some cases underlying liver cancer development are also accompanied by changes in miRNA expression levels such as hepatitis B virus infection, hepatitis C virus infection, nonalcoholic fatty liver disease (NAFLD), and alcoholic liver disease. One of miRNAs, which is associated with hepatitis virus, is miR-23 [31]. Other miRNAs also may differentiate HCC samples at the background of viral hepatitis from others, such as miR-17-92. Together with miR-21, its expression level was increased in hepatitis B virus-positive human and woodchuck HCC samples. Possibly, hepatitis B virus X and miR-17-92 share common target gene, which is c-myc, which is activated by virus and is known to be the instrument of carcinogenesis promotion of miR-17-92 [65]. Unlike HCV infection, HBV is known to induce HCC development gapping cirrhosis stage, thus making molecular predictors of cancer in this case especially required. Besides miR-122 and miR-17-92, other miRNAs, involved in HBV pathogenesis following HCC development, are miR-184, miR-185, miR-196a, miR-199a-3p, miR-210, miR-217, and miR-34a, which are involved in HBV transcription process. The expression of the last is inhibited by HBV X protein (HBx)
In case of HCV infection, there are miRNAs, which not just regulate expression of the genes, involved in virus replication, but are able to directly target the viral genome. Among these miRNAs are miR-196, miR-448, and miR-122, which stabilize the 5′ and 3′ UTRs of the HCV genome, so inhibition of this miRNA dramatically reduces the replication of HCV RNA [77, 78]. miRNAs, involved in viral replication
When it concerns alcoholic liver disease, miRNA expression profile changes especially due to increase in expression of inflammation-related miRNAs, such as miR-132, miR-155, miR-146, and miR-21, which influence alcohol/lipopolysaccharide (LPS)/TLR4 pathways, transmitting proinflammatory stimuli
Another risk factor for HCC development is NAFLD. It was revealed that miR-34a and miR-122 identified in blood serum are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively, along with miR-21, miR-125b, and miR-375 did not show significant difference in level expression between NAFLD patients and healthy controls. Serum levels of miR-34a and miR-122 were found to be significantly higher among NAFLD patients and were positively correlated with VLDL-C and triglyceride levels [83]. The other study showed the same tendency for miRNA-34a and miRNA-122, and also found a significant difference in level expression of following miRNA: miR-21and miR-451. Moreover, the serum level of miR-122 was correlated with the severity of liver steatosis; however, in the previous study, the expression levels of miR-34a and miR-122 did not correlate with the histological features of NAFLD [83]. There is at least one common signaling pathway, involving both miRNA-34a and miRNA-122, which is AMPK [21, 82]. It should be admitted that along with being possibly involved in the regulation of the same targets, miRNA-122 and miRNA-34 definitely should have similar effects as far as miRNA-122 expression is decreased in cancers including liver cancer, and miRNA-34 expression is decreased in liver cancer while being elevated in chronic hepatitis C patients. Targets and mechanisms of miRNA-34 involvement in the liver cancer development are known in less details than miRNA-122. It is supposed, that through involvement in the Sirt1/p53 pathway regulation, miRNA-34 promotes liver fibrosis in patients with HCV [84]. It is possible to speculate that with loss of the benign liver cells phenotype, malignant liver cells lose possibility of normal miRNA-34 expression as far as miRNA-34 expression is significantly decreased in liver cancer cells. One of the possible mechanisms of miRNA-34 involvement in the liver cancer development is glucose metabolism, in which LDHA, which is the target gene of miRNA-34, participates in glucose metabolism reprograming with its switch to the increased glycolysis [85]. In its turn, miRNA-122 is also indirectly involved in glucose metabolism, having Igf1R as one of its targets [63]. The other putative intersection of these two miRNAs is p53 pathway, as far as both participate in its regulation. miRNA-34 in the context of HCV fibrosis via Sirt1 regulation and miRNA-122 through cyclin G1, which results in increased p53 protein stability activity and reduction in invasion capabilities of HCC cells with elevated miRNA-122 expression [86]. Another miRNA-132, which possibly shares with miRNA-34 SIRT1 as a common target, is miRNA-132. This miRNA is elevated in the response to alcohol consumption, while
With the cancer development, differences in miRNA expression profiles smooth out as far as cancer cell phenotype and functions despite its different background development including such common features as promoted proliferation, disrupted apoptosis, and increased migratory and invasion capabilities. miRNA expression during the process of malignization changes in conformity with these demands, so far miRNA-34, being elevated in HCV liver cirrhosis, is decreased in the liver cancer cells. Obviously, all changes in miRNA expression during cancer development tend to upregulation of oncogenic miRNAs and downregulation of tumor suppressor miRNAs, and with evolution of the stage of the tumor differences in miRNA expression associated with different background liver disease level out. However, different miRNAs may be involved in the same signaling pathways or share common target genes, which is allowed by the sequence and molecular nature of miRNA—mRNA interaction—and indirect influence of miRNA on the expression levels of the genes, which are not its direct targets.
Concerning signaling pathways disrupted in HCC, almost all these pathways the regulation is double-sided: miRNA may regulate the expression of the genes and genes may regulate the expression of miRNAs. For example, TGF-β signaling may modulate miRNA expression level
miR-141 and miR-200a expression levels were shown to be decreased and serum samples from patients with liver cancer (blood samples were taken from 30 patients with liver cancer and from 30 normal subjects, RNU6 or GAPDH as internal controls). The sensitivity and specificity of the investigated miRNAs for diagnosing tumor invasion in liver cancer and comparing metastasis of patients with liver cancer were higher in combination of miR-141 and miR-200a rather than alone, although the difference between AUC values in both cases—combination and one miR regimen—had no significant changes. The possible mechanism of cancer processes modulation was explained with E-cadherin and vimentin inhibition due to STAT4 inhibition, which was firstly reported as a target gene for these miRNAs [89, 90]. The study of Dhayat et al. also showed a significant negative correlation of miR-200a and miR-200b to the expression of the mesenchymal markers Vimentin and ZEB-1 and a significant positive correlation to the epithelial marker E-cadherin. Moreover, in this study, miR-200 family was significantly downregulated in HCC samples compared to liver cirrhosis and was shown to be able to distinguish between cirrhotic and HCC tissue [90].
miR-211-5p was significantly downregulated in patients with HCC (30 pairs of HCC tissues and matched adjacent tumor-free tissues, qRT-PCR, RNU6 (miRNA) as an endogenous control), although miR-211-5p expression in liver cancer samples was not significantly different from adjacent normal samples based on TCGA cohorts, it was considerably downregulated in 30 pairs of HCC tissues compared with matched adjacent tumor-free tissues from patients in clinics or real-world cohorts. It was also shown that miR-211-5p may have a prognostic role for HCC patients: Patients with a decreased expression of miR-211-5p had poor overall survival [91]. In another study, miR-211-5p was found to be decreased in 33 out of 40 HCC tissue samples compared with the corresponding non-tumor tissues; moreover, tissues from lymph node metastases also expressed lower levels of miR-211 compared with primary HCC tissues and the adjacent normal tissue (qRT-PCR, the endogenous U6 snRNA or GAPDH as the internal control) [68]. Among miR-211-5p targets are STAB2, SPARC, ZEB2, and ACSL4, negatively regulating these genes, miR-211-5p participates in the suppression of cell proliferation, migration, and invasion in HCC tissues [92].
In contrast, miR-17/92 expression levels were shown to be highly expressed in HCC tissues compared to the non-tumor liver tissues (94 cases of HCC, 5 cases of cancer adjacent to normal hepatic tissue, and 5 cases of normal liver tissue; U6 small nuclear 2 (U6b) as an internal control, RT-PCR). In this study, it was shown that expression of miR-17-92 was negatively correlated with several target genes, including CREBL2, PRRG1, and NTN4, when analyzing the miRNA and mRNA sequencing data from the 312 hepatocellular cancer patients available from the TCGA database [68].
Expression level of miR-182-5p was also elevated in HCC tissues and its high expression level correlated with poor prognosis such as early recurrence in patients who underwent curative surgery (tissue samples from 119 patients; RT-PCR, U6 snRNA was probed as a loading control; the disease-free survival was calculated from the date of resection to the date of tumor recurrence). Promotion of HCC proliferation by miR-182-5p is partly possible due to the ability of the last to directly target 3′-UTR of FOXO3a and thus inhibits FOXO3a expression, activating AKT/FOXO3a pathway. MiR-182-5p interacts with 3`-UTR of FOXO3a by binding to the 72-79 site, but not the 914–921 site in the 3′-UTR of FOXO3a [93].
However, in almost all these pathways the regulation is double-sided: miRNA may regulate the expression of the genes, and genes may regulate the expression of miRNAs. TGF-β signaling may modulate miRNA expression level
It may seem interesting that almost none of these miRNAs were included in the list of miRNAs, implying HCC signature based on TCGA database, which consists of 540 miRNA expression profiles from 348 HCC patients, of whom 248 had early-stage and 90 had advanced-stage HCC. SVM-HCC, based on an SVM29 incorporating the feature selection algorithm IBCGAa proposed method, used a feature selection algorithm (IBCGA) to select a significant miRNA signature associated with early and advanced stages of HCC. This signature contains 23 miRNAs: in order of decreasing MED (Main Effect Difference) scores, miR-550a, miR-549, miR-518b, miR-512, miR-1179, miR-574, miR-424, miR-4286, let-7i, miR-320a, miR-17, miR-299, miR-3651, miR-2277, miR-621, miR-181c, miR-539, miR-106b, miR-1269, miR-139, miR-152, miR-2355, and miR-150. Moreover, the significance of 10 top-ranked miRNAs in distinguishing HCC tissue samples from normal tissue samples and their prognostic values were proved on different datasets [94]. For some of these miRNAs with the highest MED scores, there are known targets in the context of liver cancer development. Among direct targets of miRNA-320a, there are β-catenin, c-myc, cyclin D1, and dickkopf-1; functional studies have shown a significantly decreased capability of cell proliferation and G0/G1 growth arrest
This emphasizes the importance of working with customized algorithms and validated big datasets, when many of the aspects of the process you are studying—like miRNA involvement in carcinogenesis—stay unclear, making identification of the most promising diagnostic and/or prognostic and/or therapeutic molecules
In Table 1, there are listed miRNAs, whose expression levels are changed in the HCC development in order of mention in the text.
No. | miRNA | Decreased or increased compared with normal tissue | Possible targets | Effects of overexpression | References |
---|---|---|---|---|---|
1 | miRNA-200a | Decreased | ZEB1, ZEB2, TGF-β | Inhibition of cell proliferation and colony formation rate | [34, 35] |
2 | miRNA-21 | Increased | TGFBR2 FASLG, PTEN, HBP1, IL-12, RECK, and TIMP-3 | Promotion of tumor invasion and metastasis | [37, 39] |
3 | miR-211 | Decreased | WNT-β signaling regulation | Inhibition of cancer cells proliferation | [41] |
4 | miR-125b | Decreased | Hh | Arrest cell cycle at G₁ to S transition | [43, 44] |
5 | miRNA-199a-3p | Decreased | NOTCH, YAP1 | Inhibition of HCC cell proliferation and induction of HCC cell apoptosis | [46] |
6 | miRNA-17-5p | Decreased | ERBB3 | Inhibition of cancer cell proliferation | [48] |
7 | miRNA-637 | Decreased | Autocrine leukemia inhibitory factor (LIF), Stat 3 | Inhibition of cancer proliferation | [50] |
8 | miRNA-409 | Decreased | Jak2, STAT3 | Decreased cancer cell viability and increased apoptosis | [52] |
9 | miRNA-543 | Decreased | Jak2, Stat3 | Decreased cancer cell viability and increased apoptosis | [53] |
10 | miRNA-3662 | Decreased | HIF-1α, HK2 | Glucose metabolism transformation to Warburg effect, decreased glycolysis | [54, 55] |
11 | miRNA-122 | Decreased | Agpat 1, Dgat1, PKM2, ADAM17 | Inhibition of cancer cells proliferation | [59, 60] |
12 | miRNA-338-3p | Decreased | PKLR | Inhibition of Warburg effect | [30, 33] |
13 | miRNA-23 | Increased | G6pc, Pepck, and Fbp1 | Increased gluconeogenesis | [63] |
14 | miRNA-184 | Increased | INPPL1 | Promoting cancer cells proliferation | [70] |
15 | miRNA-196a | Increased | FOXO1 | Promotion of liver cancer cell migration and invasion | [71] |
16 | miRNA-210 | Increased | EGR3, MLL4 | Promotion of liver cancer cell proliferation | [72, 73] |
17 | miRNA-217 | Decreased | NAT2 | Inhibition of cancer cell proliferation | [74] |
18 | miRNA-34 | Decreased | AMPK, Sirt1/p53, LDHA | Inhibition of gluconeogenesis | [85] |
19 | miRNA-122 | Decreased | AMPK, Cyclin G1 | Promotion of cancer cells proliferation | [86] |
20 | miRNA-132 | Increased | SIRT1 | Promotion of cancer cell proliferation | [87] |
21 | miRNA-141 | Decreased | STAT4 | Promotion of cancer cell proliferation | [89] |
22 | miRNA-17/92 | Increased | CREBL2, PRRG1, NTN4 | Promotion of cancer cell proliferation and invasion | [68] |
23 | miRNA-182-5p | Increased | FOXO3a | Promotion of cancer cell proliferation and invasion | [93] |
24 | miRNA-320a | Decreased | β-catenin, c-myc, cyclin D1 and dickkopf-1 | Decreased capability of cell proliferation and G0/G1 growth arrest | [95] |
25 | miRNA-574-3p | Decreased | ADAM28 | Reduced cancer cell proliferation and migration | [97] |
26 | miRNA-1179 | Decreased | ZEB2 | Reduced cancer cell proliferation and migration | [98] |
27 | miRNA-550a | Increased | CPEB4 | Promotion of cancer cell proliferation | [99] |
28 | miRNA-512 | Increased | MAP3K2, MAP2K4 | Increased cancer cell proliferation rate and migration capability | [100] |
miRNAs in liver cancer development.
miRNAs play a pivotal role in liver cancer development; presumably in the early stages of HCC development, its multiple miRNA expression profiles may be distinguished depending on the etiological factor, such as HBV, HCV, NAFLD, or ALD. miRNAs are biomarkers with a huge potency as far as they are small, stable, and protected from RNases
The authors declare no conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Reynolds and Steven M. Day",coverURL:"https://cdn.intechopen.com/books/images_new/7904.jpg",editedByType:"Edited by",editors:[{id:"220737",title:"Dr.",name:"Robert",middleName:null,surname:"J. Reynolds",slug:"robert-j.-reynolds",fullName:"Robert J. 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Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",doi:"10.5772/intechopen.68944",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7768,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"59227",doi:"10.5772/intechopen.73385",title:"Differentiating Normal Cognitive Aging from Cognitive Impairment No Dementia: A Focus on Constructive and Visuospatial Abilities",slug:"differentiating-normal-cognitive-aging-from-cognitive-impairment-no-dementia-a-focus-on-constructive",totalDownloads:1353,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Constructive and visuospatial abilities in normal and in pathological aging (cognitive impairment, no dementia, CIND) are investigated. The sample includes 188 participants over 60 years of age, divided in 2 groups: healthy subjects (MMSE ≥28), without cognitive complaints, and individuals with CIND (MMSE between 24 and 27 and subjective cognitive complains). Drawing of cube and drawing of house, Benton Visual Retention Test (BVRT), and Block design are used to test the hypothesis that short visuoconstructive and visuospatial tests can distinguish normal from pathological cognitive aging in its very early stages. Results proved the discriminative sensitivity of BVRT general assessment criteria and of omissions and distortions in CIND. The diagnostic sensitivity of a modification of Moore and Wike [1984] scoring system for house and cube drawing tasks was confirmed as well. Drawing of cube and house could be used for quick screening of CIND in subjects over 60. Principal component analysis with oblimin rotation was performed to explore the different dimensions in the visuospatial and visuoconstructive abilities in old age. A four-factor structure was established, all four factors explaining 71% of the variance.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Radka Ivanova Massaldjieva",authors:[{id:"75907",title:"Associate Prof.",name:"Radka Ivanova",middleName:null,surname:"Massaldjieva",slug:"radka-ivanova-massaldjieva",fullName:"Radka Ivanova Massaldjieva"}]},{id:"59658",doi:"10.5772/intechopen.74748",title:"Ageing Better in the Netherlands",slug:"ageing-better-in-the-netherlands",totalDownloads:1193,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"The Dutch National Care for the Elderly Programme was an initiative organized by the Netherlands Organisation for Health Research and Development (ZonMw) between 2008 and 2016. The aim of the programme was to collect knowledge about frail elderly, to assess their needs and to provide person-centred and integrated care better suited to their needs. The budget of EUR 88 million was provided by the Dutch Ministry of Health, Welfare and Sports. Putting the needs of elderly people at the heart of the programme and ensuring their active participation were key to the programme’s success. The programme outcomes included the establishment of eight geriatric networks around the medical universities with 650 organisations and the completion of 218 projects. These projects, involving 43,000 elderly people and 8500 central caregivers, resulted in the completion of 45 PhD theses and the publication of more than 400 articles and the development of 300 practice toolkits, one database and a website, www.beteroud.nl. The Dutch National Care for the Elderly Programme has since developed into a movement and continues under the consortium Ageing Better, made up of eight organisations. Through the use of ambassadors, Ageing Better promotes the message that ageing is not a disease but a new phase of life.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Betty Meyboom-de Jong, Klaske Wynia and Anjo Geluk-Bleumink",authors:[{id:"224997",title:"Emeritus Prof.",name:"Betty",middleName:null,surname:"Meyboom-De Jong",slug:"betty-meyboom-de-jong",fullName:"Betty Meyboom-De Jong"},{id:"232900",title:"Dr.",name:"Klaske",middleName:null,surname:"Wynia",slug:"klaske-wynia",fullName:"Klaske Wynia"},{id:"232901",title:"Mrs.",name:"Anjo",middleName:null,surname:"Geluk-Bleumink",slug:"anjo-geluk-bleumink",fullName:"Anjo Geluk-Bleumink"}]},{id:"55890",doi:"10.5772/intechopen.69529",title:"Mindfulness Meditation and the Perception of Beauty: Implications for an Ecological Well-Being",slug:"mindfulness-meditation-and-the-perception-of-beauty-implications-for-an-ecological-well-being",totalDownloads:1428,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Meditation is a first-person method for contemplating ourselves and the world, with more than 2500 years of history, rooted in the philosophical and contemplative traditions of the east. The present chapter aims to explore this worldview in order to demonstrate its relevance to our capacity for the appreciation of beauty. To this end, the aesthetic experience, the contemplative experience and their relationship with the practice of mindfulness are analysed. We suggest that the contemplative meditative experience bestows a state of consciousness and acceptance of life which places the practitioner in a progressive encounter with a self-concept that begins to detach from a static sense of the self and from the categories that define it, so that it may be experienced as an ongoing mental event, removed from cultural ideals of beauty or positivity. The result of this de-identification from the static self is a greater degree of psychological flexibility and a more genuine way of seeing the world, leading to a new perception of the self that is connected to an experience of freedom, and contributes to one’s own well-being, as well as to that of others and of the environment.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Álvaro I. Langer, Carlos Schmidt and Edwin Krogh",authors:[{id:"199843",title:"Dr.",name:"Álvaro",middleName:null,surname:"Langer",slug:"alvaro-langer",fullName:"Álvaro Langer"},{id:"201865",title:"MSc.",name:"Carlos",middleName:null,surname:"Schmidt",slug:"carlos-schmidt",fullName:"Carlos Schmidt"},{id:"201866",title:"Dr.",name:"Edwin",middleName:null,surname:"Krogh",slug:"edwin-krogh",fullName:"Edwin Krogh"}]}],mostDownloadedChaptersLast30Days:[{id:"60564",title:"Ageing Process and Physiological Changes",slug:"ageing-process-and-physiological-changes",totalDownloads:6996,totalCrossrefCites:19,totalDimensionsCites:34,abstract:"Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7764,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"56505",title:"Aesthetics of the Naked Human Body: From Pornography (Sexualised Lust Object) to Iconography (Aesthetics of Human Nobility and Wisdom) in an Anthropology of Physical Beauty",slug:"aesthetics-of-the-naked-human-body-from-pornography-sexualised-lust-object-to-iconography-aesthetics",totalDownloads:2100,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In many religious circles and philosophies of life, the human body is excluded from the realm of spirituality and meaning. Due to a dualistic approach, nudity is viewed as merely a physical and corporeal category. In social media, there is the real danger that the naked human body is exploited for commercial gain. Advertisements often leave the impression that the body, very specifically the genitals, is designed merely for physical desire and corporeal chemistry. They become easily objects for lust, excluded from the beauty of graceful existence and noble courage. It is argued that the naked human body is not designed for pornographic exploitation and promiscuous sensuality but for compassionate intimacy and nurturing care in order to instil a humane dimension in human and sexual encounters. In this regard, antiquity and the Michelangelesque perspective can contribute to a paradigm shift from abusive exploitation to the beauty of vulnerable sensitivity. In order to foster an integrative approach to theory formation in anthropology, the methodology of stereometric thinking is proposed.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Daniel J Louw",authors:[{id:"200645",title:"Prof.",name:"Daniel",middleName:"Johannes",surname:"Louw",slug:"daniel-louw",fullName:"Daniel Louw"}]},{id:"56059",title:"A Plastic Surgeon’s Perspective on Stereotyping and the Perception of Beauty",slug:"a-plastic-surgeon-s-perspective-on-stereotyping-and-the-perception-of-beauty",totalDownloads:1918,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"In the world of plastic surgery, misconceptions may lead to irrational requests or outcomes not appreciated by patients. Those who manage aesthetics should always listen and recognize the variability of cultural identities, desires, attitudes, anxieties and uncertainties of the patient. Emerging from a diversity of cultures and its transforming trends, the scope of cosmetic surgery and its practice reflect not only the individual’s personality, but also the culture as a whole. When counseling an individual, one has to recognize that even in groups of seemingly identical social or cultural standards; there are subtle differences in expectations. To illustrate the potential for inaccuracy of ethnic profiling in the field of plastic surgery authors quote their own work on Asian subjects and facial beauty and resort to experience of others. To reaffirm their opinion and to exemplify how sometimes “fine” differences in the perception of beauty exist, an original study that evaluates the preferences among selected groups of Latina women in respect to buttock aesthetics has been included. This dissertation will focus on how cultural factors influence beauty perception; strengthen the fact that beauty is in the eye of the beholder and how variable differences exist even between small subgroups.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Johanna D’Agostino and Marek Dobke",authors:[{id:"17590",title:"Dr.",name:"Marek K.",middleName:null,surname:"Dobke",slug:"marek-k.-dobke",fullName:"Marek K. Dobke"},{id:"201244",title:"Dr.",name:"Johanna",middleName:null,surname:"D'Agostino",slug:"johanna-d'agostino",fullName:"Johanna D'Agostino"}]},{id:"80326",title:"Anti-Senescence Therapy",slug:"anti-senescence-therapy",totalDownloads:110,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The development of therapeutic strategies aimed at the aging process of cells has attracted increasing attention in recent decades due to the involvement of this process in the development of many chronic and age-related diseases. Interestingly, preclinical studies have shown the success of a number of anti-aging approaches in the treatment of a range of chronic diseases. These approaches are directed against aging processes such as oxidative stress, telomerase shortening, inflammation, and deficient autophagy. Many strategies has been shown to be effective in delaying aging, including antiaging strategies based on establishing healthy lifestyle habits and pharmacological interventions aimed at disrupting senescent cells and senescent-associated secretory phenotype. Caloric restriction and intermittent fasting were reported to activate autophagy and reduce inflammation. In turn, immune-based strategies, senolytic agents, and senomorphics mediate their effects either by eliminating senescent cells through inducing apoptosis or by disrupting pathways by which senescent cells mediate their detrimental effects. In addition, given the association of the decline in the regenerative potential of stem cells with aging, many experimental and clinical studies indicate the effectiveness of stem cell transplantation in preventing or slowing the progress of age-related diseases by enhancing the repairing mechanisms and the secretion of many growth factors and cytokines.",book:{id:"10935",slug:null,title:"Mechanisms and Management of Senescence",fullTitle:"Mechanisms and Management of Senescence"},signatures:"Raghad Alshadidi",authors:null}],onlineFirstChaptersFilter:{topicId:"235",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82112",title:"Comparative Senescence and Lifespan",slug:"comparative-senescence-and-lifespan",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.105137",abstract:"The word senescence is derived from the Latin word “senex” (meaning old). In biology, senescence is a process by which a cell ages and permanently stops dividing. Senescence is a natural universal phenomenon affecting all living organisms (e.g., humans, animals, and plants). It is the process of growing old (aging). The underlying mechanisms of senescence and aging at the cellular level are not fully understood. Senescence is a multifactorial process that can be induced by several stimuli including cellular stress, DNA damage, telomere shortening, and oncogene activation. The most popular theory to explain aging is the free radical theory. Senescence plays a role in the development of several age-related chronic diseases in humans (e.g., ischemic heart disease, osteoporosis, and cancer). Lifespan is a biological characteristic of every species. The lifespan of living organisms ranges from few hours (with mayfly) to potential eternity (with jellyfish and hydra). The maximum theoretical lifespan in humans is around 120 years. The lifespan in humans is influenced by multiple factors including genetic, epigenetic, lifestyle, environmental, metabolic, and endocrine factors. There are several ways to potentially extend the lifespan of humans and eventually surpass the maximum theoretical lifespan of 120 years. The tools that can be proposed include lifestyle, reduction of several life-threatening diseases and disabilities, hormonal replacement, antioxidants, autophagy inducers, senolytic drugs, stem cell therapy, and gene therapy.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Hassan M. Heshmati"},{id:"81638",title:"Aging and Neuropsychiatric Disease: A General Overview of Prevalence and Trends",slug:"aging-and-neuropsychiatric-disease-a-general-overview-of-prevalence-and-trends",totalDownloads:30,totalDimensionsCites:0,doi:"10.5772/intechopen.103102",abstract:"The increasing trend of life-expectancy is becoming a significant demographic, societal and economic challenge. Currently, global number of people above sixty years of age is 900 million, while United Nations expect this number to rise to over 1.4 billion in 2030 and over 2.5 billion by 2050. Concordant to this trend, numerous physiological changes are associated with aging and brain-related ones are associated with neuropsychiatric diseases. The main goal of this chapter is to identify the most important neuropsychiatric diseases to assess in older patients to help to promote health and prevent diseases and complications associated with chronic illness, as these changes are progressive and require important psychological and setting-related social adjustments. Findings identify several health-aspects highly present in elderly: stroke, white matter lesions, dementia rise with age, changes in levels of neurotransmitters and hormones, depression as well as the bereavement following loss of the loved one, and the most common neurodegenerative disease—Alzheimer’s disease and Parkinson’s. In conclusion, studying the aging process should include all developmental, circumstantial, and individual aspects of aging. This offers opportunities to improve the health of elderly by using a wide range of skills and knowledge. Thus, further studies are necessary to elucidate what can be done do to improve the aging process and health of elderly in the future.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Jelena Milić"},{id:"80326",title:"Anti-Senescence Therapy",slug:"anti-senescence-therapy",totalDownloads:110,totalDimensionsCites:0,doi:"10.5772/intechopen.101585",abstract:"The development of therapeutic strategies aimed at the aging process of cells has attracted increasing attention in recent decades due to the involvement of this process in the development of many chronic and age-related diseases. Interestingly, preclinical studies have shown the success of a number of anti-aging approaches in the treatment of a range of chronic diseases. These approaches are directed against aging processes such as oxidative stress, telomerase shortening, inflammation, and deficient autophagy. Many strategies has been shown to be effective in delaying aging, including antiaging strategies based on establishing healthy lifestyle habits and pharmacological interventions aimed at disrupting senescent cells and senescent-associated secretory phenotype. Caloric restriction and intermittent fasting were reported to activate autophagy and reduce inflammation. In turn, immune-based strategies, senolytic agents, and senomorphics mediate their effects either by eliminating senescent cells through inducing apoptosis or by disrupting pathways by which senescent cells mediate their detrimental effects. In addition, given the association of the decline in the regenerative potential of stem cells with aging, many experimental and clinical studies indicate the effectiveness of stem cell transplantation in preventing or slowing the progress of age-related diseases by enhancing the repairing mechanisms and the secretion of many growth factors and cytokines.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Raghad Alshadidi"},{id:"79828",title:"Cellular Senescence in Bone",slug:"cellular-senescence-in-bone",totalDownloads:119,totalDimensionsCites:0,doi:"10.5772/intechopen.101803",abstract:"Senescence is an irreversible cell-cycle arrest process induced by environmental, genetic, and epigenetic factors. An accumulation of senescent cells in bone results in age-related disorders, and one of the common problems is osteoporosis. Deciphering the basic mechanisms contributing to the chronic ailments of aging may uncover new avenues for targeted treatment. This review focuses on the mechanisms and the most relevant research advancements in skeletal cellular senescence. To identify new options for the treatment or prevention of age-related chronic diseases, researchers have targeted hallmarks of aging, including telomere attrition, genomic instability, cellular senescence, and epigenetic alterations. First, this chapter provides an overview of the fundamentals of bone tissue, the causes of skeletal involution, and the role of cellular senescence in bone and bone diseases such as osteoporosis. Next, this review will discuss the utilization of pharmacological interventions in aging tissues and, more specifically, highlight the role of senescent cells to identify the most effective and safe strategies.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Danielle Wang and Haitao Wang"},{id:"79668",title:"Identification of RNA Species That Bind to the hnRNP A1 in Normal and Senescent Human Fibroblasts",slug:"identification-of-rna-species-that-bind-to-the-hnrnp-a1-in-normal-and-senescent-human-fibroblasts",totalDownloads:81,totalDimensionsCites:0,doi:"10.5772/intechopen.101525",abstract:"hnRNP A1 is a member of the hnRNPs (heterogeneous nuclear ribonucleoproteins) family of proteins that play a central role in regulating genes responsible for cell proliferation, DNA repair, apoptosis, and telomere biogenesis. Previous studies have shown that hnRNPA1 had reduced protein levels and increased cytoplasmic accumulation in senescent human diploid fibroblasts. The consequence of reduced protein expression and altered cellular localization may account for the alterations in gene expression observed during senescence. There is limited information for gene targets of hnRNP A1 as well as its in vivo function. In these studies, we performed RNA co-immunoprecipitation experiments using hnRNP A1 as the target protein to identify potential mRNA species in ribonucleoprotein (RNP) complexes. Using this approach, we identified the human double minute 2 (HDM2) mRNA as a binding target for hnRNP A1 in young and senescent human diploid fibroblasts cells. It was also observed that alterations of hnRNP A1 expression modulate HDM2 mRNA levels in young IMR-90 cells. We also demonstrated that the levels of HDM2 mRNA increased with the downregulation of hnRNP A1 and decrease with the overexpression of hnRNP A1. Although we did not observe a significant decrease in HDM2 protein level, a concomitant increase in p53 protein level was detected with the overexpression of hnRNP A1. Our studies also show that hnRNP A1 directly interacts with HDM2 mRNA at a region corresponding to its 3′ UTR (untranslated region of a gene). The results from this study demonstrate that hnRNP A1 has a novel role in participating in the regulation of HDM2 gene expression.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Heriberto Moran, Shanaz A. Ghandhi, Naoko Shimada and Karen Hubbard"},{id:"79295",title:"Genetic and Epigenetic Influences on Cutaneous Cellular Senescence",slug:"genetic-and-epigenetic-influences-on-cutaneous-cellular-senescence",totalDownloads:135,totalDimensionsCites:0,doi:"10.5772/intechopen.101152",abstract:"Skin is the largest human organ system, and its protective function is critical to survival. The epithelial, dermal, and subcutaneous compartments are heterogeneous mixtures of cell types, yet they all display age-related skin dysfunction through the accumulation of an altered phenotypic cellular state called senescence. Cellular senescence is triggered by complex and dynamic genetic and epigenetic processes. A senescence steady state is achieved in different cell types under various and overlapping conditions of chronological age, toxic injury, oxidative stress, replicative exhaustion, DNA damage, metabolic dysfunction, and chromosomal structural changes. These inputs lead to outputs of cell-cycle withdrawal and the appearance of a senescence-associated secretory phenotype, both of which accumulate as tissue pathology observed clinically in aged skin. This review details the influence of genetic and epigenetic factors that converge on normal cutaneous cellular processes to create the senescent state, thereby dictating the response of the skin to the forces of both intrinsic and extrinsic aging. From this work, it is clear that no single biomarker or process leads to senescence, but that it is a convergence of factors resulting in an overt aging phenotype.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Tapash Jay Sarkar, Maiko Hermsmeier, Jessica L. Ross and G. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null,editorialBoard:[{id:"190041",title:"Dr.",name:"Jose",middleName:null,surname:"Gutierrez Fernandez",slug:"jose-gutierrez-fernandez",fullName:"Jose Gutierrez Fernandez",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"University of Granada",institutionURL:null,country:{name:"Spain"}}},{id:"156556",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Mascellino",slug:"maria-teresa-mascellino",fullName:"Maria Teresa Mascellino",profilePictureURL:"https://mts.intechopen.com/storage/users/156556/images/system/156556.jpg",institutionString:"Sapienza University",institution:{name:"Sapienza University of Rome",institutionURL:null,country:{name:"Italy"}}},{id:"164933",title:"Prof.",name:"Mónica Alexandra",middleName:null,surname:"Sousa Oleastro",slug:"monica-alexandra-sousa-oleastro",fullName:"Mónica Alexandra Sousa Oleastro",profilePictureURL:"https://mts.intechopen.com/storage/users/164933/images/system/164933.jpeg",institutionString:"National Institute of Health Dr Ricardo Jorge",institution:{name:"National Institute of Health Dr. Ricardo Jorge",institutionURL:null,country:{name:"Portugal"}}}]},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",slug:"felix-bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:null,institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Islamic Azad University, Tehran",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"188881",title:"Dr.",name:"Fernando José",middleName:null,surname:"Andrade-Narváez",slug:"fernando-jose-andrade-narvaez",fullName:"Fernando José Andrade-Narváez",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRIV7QAO/Profile_Picture_1628834308121",institutionString:null,institution:{name:"Autonomous University of Yucatán",institutionURL:null,country:{name:"Mexico"}}},{id:"269120",title:"Dr.",name:"Rajeev",middleName:"K.",surname:"Tyagi",slug:"rajeev-tyagi",fullName:"Rajeev Tyagi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRaBqQAK/Profile_Picture_1644331884726",institutionString:"CSIR - Institute of Microbial Technology, India",institution:null},{id:"336849",title:"Prof.",name:"Ricardo",middleName:null,surname:"Izurieta",slug:"ricardo-izurieta",fullName:"Ricardo Izurieta",profilePictureURL:"https://mts.intechopen.com/storage/users/293169/images/system/293169.png",institutionString:null,institution:{name:"University of South Florida",institutionURL:null,country:{name:"United States of America"}}}]},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:302,paginationItems:[{id:"280338",title:"Dr.",name:"Yutaka",middleName:null,surname:"Tsutsumi",slug:"yutaka-tsutsumi",fullName:"Yutaka Tsutsumi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/280338/images/7961_n.jpg",biography:null,institutionString:null,institution:{name:"Fujita Health University",country:{name:"Japan"}}},{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:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{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. 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