",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. 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He also holds two PhDs in Mathematics and Prognostics from the Lebanese University, Lebanon, and Aix-Marseille University, France. Dr. Abou Jaoudé's broad research interests are in the field of applied mathematics. 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1. Introduction
Establishing and maintaining pregnancy requires a finely regulated series of physiological events involving mother, fetus, and placenta. The essential role of steroid hormones in the production and maintenance of many of these changes is well characterized. For example, important effects of progesterone include preparation of the endometrium for implantation [1], modulation of the maternal immune response to tolerate the fetal allograft, maintenance of myometrial quiescence [2], and preparation of mammary glands for lactation. Estrogens appear to influence uterine blood flow and neovascularization, increase the expression of critical proteins that are involved in progesterone production and steroid metabolism and participate in preparation of mammary glands for lactation [3, 4]. Throughout pregnancy, levels of maternal circulating androgens, including testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and androstenedione (A4) increase, with concentrations three-fold higher by the third trimester when compared to non-pregnant levels in women [5]. Although T is a well-known precursor for estrogens (E2) synthesis, the placenta can both be a source and a target for androgens. The goal of this chapter is to summarize what is known about androgens and androgen receptor in pregnancy and compare it between species and between different types of placenta.
2. Placenta classification
The placenta is a multifunctional, transitory organ that mediates transport of nutrients and waste, gas exchange, and endocrine signaling. In fact, placental secretion of hormones is critical for maintenance of pregnancy, as well as growth and development of a healthy offspring. Despite fulfilling similar functions, there is a wide range of diversity in placental anatomo-histology among species.
During early embryogenesis, the first cells to differentiate are trophoblast cells, which form the chorion or fetal portion of the placenta. Villous trophoblast cells have two distinct cell populations; undifferentiated cytotrophoblast cells and differentiated syncytiotrophoblast tissue. The syncytiotrophoblast tissue is a continuous, multinucleated, specialized layer of epithelial cells, which covers the villous surface and is in direct contact with maternal blood. This layer is formed by fusion of cytotrophoblast cells.
Placental gross morphological classification is based on the shape and the area of contact between fetal and maternal tissue [6]. There are four commonly describe placental shapes among mammals:
Diffuse placenta, present in the horse and pig, has chorionic villi in contact with the uterine endometrium throughout the entire surface of the allantochorion, forming either folds (pig) or microcotyledons (horse).
Cotyledonary placenta, present in ruminants, is made up of multiple discrete areas of attachment called cotyledons, which are formed by the interaction between the fetal allantochorion and the maternal endometrium. The fetal side of this type of placenta is called cotyledons, the maternal side is called caruncles, and the cotyledon-caruncle complexes are known as placentomes.
Zonary placenta, present in carnivores such as dogs and cats, has the shape of a complete (dog and cat) or incomplete band (ferrets and raccoons) of tissue surrounding the chorionic sack.
Discoid placenta, present in rodents and primates, is formed by a collection of villi on a single (mice and human) or double (rabbit) disc.
In addition to the gross morphological classification, placentas are also categorized by histology (Figure 1) which is based on the different number of cell layers separating fetal from maternal circulation [7]. Before the placenta is formed, there are a total of six layers of tissue separating maternal and fetal blood. Three of these layers are fetal extraembryonic membranes in the chorioallantoic placenta of all mammals, all of which are components of the mature placenta. These three layers include endothelium lining allantoic capillaries, connective tissue in the form of chorioallantoic mesoderm, and chorionic epithelium, derived from trophoblast cells. There are also three layers on the maternal side, but the number of these layers which are retained after placentation varies greatly among species. The three potential maternal layers in a placenta are endothelium lining endometrial blood vessels, connective tissue of the endometrium, and endometrial epithelial cells.
Figure 1.
Histological classification of the placenta.
Based on this degree of separation, or number of layers separating the fetal and maternal tissues, there are four different types of placenta (see Figure 1):
Epitheliochorial placenta, present in pig and horse, consists of all six layers separating maternal from fetal blood throughout gestation. The trophoblast cells make contact with the uterine epithelium forming microcotyledons (horse) or chorionic folds (pig). Microcotyledons contain highly vascularized chorionic villi that extend into elaborate invaginations of the endometrium. Chorionic folds are formed by the lining of the chorionic villi into the wrinkled surface of the uterine epithelium.
Synepitheliochorial placenta, present in ruminants, contains the same layers as an epitheliochorial placenta. In this type of placenta, the uterine epithelium is modified by invasion and fusion of binucleate cells forming the syncytium, which contains embryonic and maternal nuclei. More recently, multinucleated trophoblast giant cells (TGC), formed by incomplete cytokinesis of mononucleated trophoblast cells, are believed to remove endometrial epithelial cells and fuse and contribute to the syncytial trophoblast layer [8].
Endotheliochorial placenta, present in carnivores (cats and dogs), is formed when the endometrial epithelium is disrupted during placentation, and fetal chorionic epithelial cells come in contact with maternal endothelial cells. During implantation, cytotrophoblast cells surround the central third of the chorioallantois and proliferate to form a syncytium called the syncytiotrophoblast layer. The syncytiotrophoblast layer erodes through the endometrial epithelium and grows around maternal capillaries. Initially, the invading fetal cells are in the form of villi, but villi soon coalesce to form a labyrinthine-type placenta. For this reason, only four tissue layers separate the maternal from the fetal blood.
Hemochorial placenta, present in humans and rodents, is the most invasive form of placentation. Fetal chorionic epithelium is bathed in maternal blood because chorionic villi have invaded through endometrial epithelium and eroded through maternal endothelium. The number of trophoblast layers in contact with the maternal circulation shows variation between species. It is hemomonochorial in humans, with one layer of syncytiotrophoblast, and hemodichorial in primates, with one layer of syncytiotrophoblast upon one layer of cytotrophoblast cells. Finally, it is hemotrichorial in rodents with one layer of cytotrophoblast and two layers of syncytiotrophoblast separating maternal and fetal blood.
3. Placenta steroidogenesis
A key function of the placenta is the secretion of hormones. Like other steroid hormones, T is derived from cholesterol and the synthesis involves several enzymatic steps. The first and fundamental step in its biosynthesis involves the oxidative breakdown of the cholesterol side chain by the enzyme P450scc (side-chain cleavage), a mitochondrial cytochrome oxidase, resulting in the loss of six carbon atoms to give rise to pregnenolone. Only certain cell types in humans are capable of pregnenolone synthesis, including testicular Leydig cells, ovarian theca and corpus luteal cells, placental trophoblast cells, cells of the adrenal cortex, and specific cells in the brain, such as the pyramidal and granular neurons of the hippocampus and the Purkinje cells from the cerebellum [9]. The resulting pregnenolone is either converted to progesterone or 17 α-hydroxypregnenolone via 3β-hydroxysteroid dehydrogenase (HSD3B) or cytochrome P450 17A1 (CYP17A1), respectively. Progesterone is secreted into maternal circulation, and 17α-hydroxypregnenolone can be metabolized to DHEA via CYP17A1. DHEA is oxidized into A4 via HSD3B. A4 is then reduced to 5 α-androstenedione via 5 α-reductase (SRD5A). DHEA and A4 can be converted by 17 β-hydroxysteroid dehydrogenase into androstenediol and T, respectively. Subsequently, T is converted into DHT via 5 α-reductase (SRD5A). T and 5 α-androstenedione can further be metabolized to estrogens via aromatase (CYP19A1) [10]. A summarized overview of placental steroidogenesis is provided in Figure 2.
Figure 2.
Summarized overview of the functional interaction between the placental, maternal and fetal compartments for the biosynthesis of progesterone, estrogens and androgens by the human placenta. Progesterone is produced mainly from maternal cholesterol. Progesterone can be metabolized into DHEA by the maternal and fetal adrenal gland. DHEA can be converted into T. Subsequently, T can further be metabolized to estrogens via aromatase (CYP19A1). In horses, the placenta does not appear to express P450c17 and thus cannot convert de novo c21 progestogens (pregnenolone and progesterone) to the c19 androgens (DEHA and A4). It is for this reason that the reaction occurs in the fetal adrenal.
Androgens are synthesized in tissues where 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17) exists. This enzyme is located in different tissues such as fetal and maternal adrenal glands, fetal ovaries and testes, and the corpus luteum, depending on to the animal species. In non-pregnant woman, 50% of all DHEA is secreted by the adrenal glands, 20% from the ovarian theca and 30% is derived from metabolism of circulating DHEA sulfate [11]. Adrenal glands and ovaries produce equal amounts of A4, with the total daily production rate 1.4-6.2 mg/day [12]. 50% of T is synthesized in the ovaries and adrenals and the other half is produced from A4 in the peripheral tissues. Daily production rate of T in non-pregnant women is in the order of 0.1–0.4 mg/day. Finally, the conversion of T to DHT occurs in peripheral tissues, such as ovaries and skin, with a daily production rating between 4.3 and 12.5 mg/day.
During pregnancy, an additional source of androgens comes from the fetus and placenta (Figure 2). Androgens are principally synthesized in the corpus luteum during early stages of gestation in rats and dogs and this function is taken over by the placenta in late stages of gestation in rats [13]. In sheep and goats, P450c17 is present in the placenta [14]. Some studies revealed that the absence of P450c17 in human and horse placentas results in negligible androgen synthesis [15]. However, protein and mRNA levels of CYP17A1 have been detected in primary human trophoblast cells and the human trophoblast cell line JEG-3 and trophoblast cells were able to generate testosterone de novo [16]. Placentas associated with a male fetus at term have increased expression of 5 α-reductase compared to a female fetus [17]. This enzyme is involved in reducing T to DHT, a potent androgen with a higher binding affinity to AR than T, suggesting the placenta may play a role in the hormonal differences between pregnancies between female and male fetuses.
In horses, the placenta does not appear to express P450c17 and thus cannot convert de novo c21 progestogens (pregnenolone and progesterone) to the c19 androgens (DEHA and A4). In this case, the fetal gonads are the main androgen source as estrogens precursor during mid to late gestation in the horse. Removal of fetal gonads results in an immediate fall in maternal plasma concentrations of conjugated and unconjugated estrogens whereas progestogens levels remain unchanged [18].
4. Androgen signaling and placenta function
To exert a cellular response, steroid hormones need to bind to either a membrane receptor or an intracellular, nuclear or cytoplasmic receptor. T and DHT can bind to either type of receptor, AR (encoded by AR, in the human Xq11-12), or a membrane-bound receptor, such as G protein-coupled receptor family C group 6 member A (GPRC6A) [19]. DHEA and A4 require conversion to T or DHT to exert their androgenic effects.
AR is expressed at all levels of the female hypothalamic-pituitary-gonadal axis, including the brain, ovarian stroma, ovarian follicles and corpus luteum. Furthermore, AR is present in first trimester and term placenta, and localizes to the cytosol of placental villi, and in cytotrophoblast, differentiated syncytiotrophoblast, and placental stroma [20]. In ruminant placentomes, nuclear signals are predominantly observed in invasive TGC and uninucleate trophoblast cells, stromal cells of the chorionic villi, caruncular epithelial, and stromal cells during late gestation [21, 22].
AR belongs to the steroid hormone intracellular receptor family. Exon 1 of the AR gene encodes the N-terminal domain, which contains an activation function 1 (AF1) region that interacts with coregulatory proteins to enhance transcriptional regulation of AR target genes. Exons 2 and 3 encode two distinct zinc-fingers (DNA-binding domain) required for interaction with a palindromic androgen response elements (ARE) of the core sequence, 5′-TGTTCT-3′, separated by 3 nucleotides located within the promoter regions of AR target genes. The remaining exons encode a hinge region which contains the nuclear localization signal, and the ligand binding domain [23].
When localized to the cytoplasm, AR is bound by a number of chaperone proteins including heat shock protein 90 (Hsp90) as well as immunophilins. When ligands, T or DHT, bind to AR, there is a conformational change which exposes the nuclear localization signal, allowing the interaction with importin-α, which facilitates nuclear translocation. Once inside the nucleus, two subunits of the AR dimerize and bind the ARE on promoter regions of AR-target genes, resulting in transcriptional regulation, leading to either activation or suppression of expression. Co-regulatory proteins, such as histone lysine demethylases (KDMs), modulate transcriptional activity of AR-target genes. In sheep for example, KDMs have been found to act as co-regulators in trophoblast cells [22, 24]. This interaction with regulator factors is critical for signaling processes in the placenta.
Androgens are known to stimulate proliferation of human umbilical vein endothelial cells, indicating a key role for androgens during pregnancy. During establishment of pregnancy, androgens play a role in embryo implantation. Early in pregnancy, before implantation, T is converted to DHT which regulates transcription of factors necessary for initiation of decidualization and early endometrial receptivity. Near the time of implantation, T itself promotes endometrial remodeling, and soon after implantation it serves as an important precursor for E2 which regulates vascular remodeling [25]. Studies in mice reveal that insufficient androgens may delay embryo implantation, whereas excess androgens lead to aberrant gene expression at implantation sites.
Studies on ovine placentas revealed vascular endothelial growth factor A (VEGFA) expression to be androgen responsive, and androgens are thought to regulate the expression of VEGFA and play a key role in placental angiogenesis [21, 23]. More specifically, AR and the KDM1A coregulator are recruited to an ARE in the ovine VEGFA promoter. On gestational day 90, placenta VEGFA mRNA and VEGFA and AR protein levels increased in testosterone-treated ewes compared to control placentas [22].
In addition to the classical genomic intracellular AR mediated signaling pathways, androgens also act through membrane receptors. GPRC6A is a G protein-coupled receptor (GPCR) that functions as a membrane receptor for small amino acids, cations, osteocalcin, and androgens [26]. GPRC6A is known to have a long extracellular domain to allow for the binding of these different ligands [26]. GPRC6A mediates the effects of osteocalcin, a protein hormone released by osteoblasts, and results in the activation of the cAMP pathway and subsequently, testosterone synthesis by the Leydig cells of the testis. GPRC6A ligand binding can result in the activation of the Gαs, Gαi, and Gαq pathways (Figure 3). The presence of GPRC6A has been identified in placental trophoblast cell membranes, indicating the possibility of androgens eliciting a non-genomic effect on cells of the placenta.
Figure 3.
Androgen signaling through GPRC6A in target tissue. Image created with BioRender.com.
Another membrane receptor that androgens elicit a non-genomic effect through is Zrt- and Irt-like protein 9 (ZIP9) [27]. ZIP9 is a zinc transporter that also acts as a receptor for androgens via G-protein coupling. Studies have revealed the presence of ZIP9 in ovarian tissue of Atlantic croakers, and act as a receptor for androgens inducing apoptosis in follicular cells, as well as promoting zinc uptake. Studies also show a similar action in breast and prostate tissue [28]. Ultimately, these two studies reveal that androgens binding to ZIP9 results in the activation of pro-apoptotic genes and the regulation of zinc homeostasis within target tissues [28].
Similarly, Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8) and Oxoeicosanoid receptor 1 (OXER1) bind a variety of ligands including androgens [29]. However, their expression during pregnancy or in placental cells is currently unknown.
5. Androgens and pregnancy
Androgens play a fundamental role in female physiology, particularly during pregnancy. In women, androgens are synthesized by cells within the ovaries, the adrenal glands, fat, and also in placenta, acting in an endocrine or paracrine fashion [30]. DHEA, mainly from the adrenal glands, acts as a crucial precursor for E2 and T in the ovary and other target tissues such as fat [31]. Depending on the intracellular availability of steroidogenic enzymes in target tissues, DHEA is converted to A4 which is a precursor for T, both of which can be aromatized to estrogens [32]. Some studies have reported an elevated level of T during pregnancy. An increase in T levels occurs from the first trimester of pregnancy, becoming more pronounced towards the third trimester, being three-folds higher than observed in non-pregnant women (Table 1) [36]. In contrast, maternal circulating DHEA levels decrease in pregnant women due to it being converted to T and E2 [37].
Humans
Testosterone (ng/ml)
Pimiparous
Multiparous
1st trimester
1.34
0.66
2nd trimester
1.98
0.73
3rd trimester
2.56
0.71
7-20 wks
0.69
21-40 wks
1.095
Horse
Days from ovulation
0-35
0.04
35-120
0.14
180–240
2.5
240-300
3.5
>300
1.5
Cow
Days from ovulation
0-90
0.020-0.050
90-270
0.22
Table 1.
Testosterone serum levels during pregnancy in human [33], horses [34], and cows [35].
Steroid production varies widely among species, with these differences becoming more pronounced during pregnancy. Each species have their own distinct pattern of steroid serum levels, steroidogenic enzymes, receptors, and transporters to support their individual physiological requirements. For example, in dairy cows, maternal serum T levels increase ~100-fold during the last trimester of gestation (Table 1), as well as a ~50-fold increase in milk testosterone levels [38].
In the horse, T elevation during pregnancy presents a biphasic curve (Table 1). The first elevation is caused by luteal androgen production, which is stimulated by equine chorionic gonadotropin (eCG). The late rise and fall are temporally related to the development and regression, respectively, of the fetal gonads. The equine placenta has little capacity to synthesize androgens, as it lacks CYP17A1. Hence, androgens in the form of DHEA are substrates for E2 synthesis, and must be supplied mostly by fetal gonads, forming a true feto-placental unit [39].
As androgen levels increase during pregnancy, the mother and developing fetuses usually are protected from excess bioactive androgens by increased secretion of sex hormone-binding and placental aromatase, which converts T into E2. Hyperandrogenism can result from a number of conditions, the most common being luteomas and theca-lutein cysts within the ovary. Luteomas are benign tumors that occur during pregnancy with excess androgen production in 25-35% of the cases [33, 40, 41]. These often go unnoticed and in most cases are non-virilizing.
Additional causes of excess androgen production during pregnancy are conditions such as polycystic ovarian syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, and congenital adrenal hyperplasia (CAH). Both conditions result in pregnancy complications, including pregnancy induced hypertension and pre-eclampsia, a human pregnancy syndrome characterized by the onset of hypertension and proteinuria after 20 weeks of gestation, and can lead to maternal or fetal mortality [42]. In humans, clinical observations have established that women with PCOS exhibit similar features as seen in classical 21-hydroxylase deficiency in CAH, such as anovulation, ovarian hyperandrogenism, LH hypersecretion, polycystic appearing ovaries, and insulin resistance, despite normalization of adrenal androgen excess after birth [43]. Furthermore, animal studies have demonstrated that intrauterine exposure to excessive amounts of androgens can lead to development of PCOS after birth (reviewed in [44, 45]). In fact, prenatal androgenization in pregnant ewes has revealed reproductive and metabolic phenotypes in female offspring that closely resemble PCOS in women. These observations suggest that androgen excess during early life, whether derived from fetal or maternal sources, may provide one possible mechanism to explain the occurrence of PCOS in adulthood.
Less common causes leading to androgen excess during pregnancy include placental aromatase deficiency. Aromatase is encoded by the CYP19A1 gene, and is responsible for converting T to E2. At least 10 different promoters have been identified in its regulatory region, enabling regulation in a tissue-specific manner [46]. Mutations in CYP19A1 prevent aromatization of testosterone, leading to hyperandrogenism and phenotypes similar to androgen excess, including maternal and fetal virilization and development of ambiguous genitalia at birth [47]. Of particular interest is the observation that placental aromatase deficiency is associated with pre-eclampsia [48, 49]. Women with pre-eclampsia have significantly lower levels of placental aromatase, and significantly lower levels of both 17β-estradiol:testosterone and estrone:androstenedione ratios, as well as higher levels of T. In fact, this placental defect in steroidogenesis appears before clinical symptoms of pre-eclampsia and thus may serve as a diagnostic marker.
6. Conclusions
The focus of this chapter was on androgens and their potential role in pregnancy and placental development and function. Normal pregnancy in women is associated with increased maternal serum levels of androgens, which are derived from the adrenal glands, adipose tissue, ovaries, and placenta. Species differences in androgen production exist reflecting species-specific needs for pregnancy maintenance and/or placental function. Furthermore, the placenta contains classical androgen receptors as well as non-classical membrane receptors, indicating the placenta is a target of androgen signaling. Preliminary and ongoing studies suggest a role for androgen signaling in trophoblast cell differentiation and placental angiogenesis.
Acknowledgments
The authors would like to thank Ms. Coni Hoerndli, Science Design (chsciencedesign.com), for help with Figures 1 and 2. Funding for this work was provided and supported by Agriculture and Food Research Initiative Competitive Grant 2019-67015-29000 from the U.S. Department of Agriculture (USDA) National Institute of Food and Agriculture.
\n',keywords:"pregnancy, placenta, testosterone, dihydrotestosterone, androgen receptor",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73546.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73546.xml",downloadPdfUrl:"/chapter/pdf-download/73546",previewPdfUrl:"/chapter/pdf-preview/73546",totalDownloads:405,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:1,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:56,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"August 28th 2020",dateReviewed:"September 12th 2020",datePrePublished:"November 10th 2020",datePublished:"May 5th 2021",dateFinished:"October 10th 2020",readingETA:"0",abstract:"The placenta is a multifunctional, transitory organ that mediates transport of nutrients and waste, gas exchange, and endocrine signaling. In fact, placental secretion of hormones is critical for maintenance of pregnancy, as well as growth and development of healthy offspring. In this chapter, the role of androgens in placental development and function is highlighted. First, a brief summary will be provided on the different mammalian placental types followed by an overview of placental steroidogenesis. Next, the chapter will focus on genomic and non-genomic androgen signaling pathways. Finally, an overview will be provided on the current status of androgen signaling in the placenta during normal and abnormal pregnancies.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73546",risUrl:"/chapter/ris/73546",book:{id:"10313",slug:"reproductive-hormones"},signatures:"Agata M. Parsons Aubone, River Evans and Gerrit J. Bouma",authors:[{id:"276521",title:"Ph.D.",name:"Gerrit J.",middleName:null,surname:"Bouma",fullName:"Gerrit J. 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Placenta classification",level:"1"},{id:"sec_3",title:"3. Placenta steroidogenesis",level:"1"},{id:"sec_4",title:"4. Androgen signaling and placenta function",level:"1"},{id:"sec_5",title:"5. Androgens and pregnancy",level:"1"},{id:"sec_6",title:"6. Conclusions",level:"1"},{id:"sec_7",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Itskovitz J, Hodgen GD. Endocrine basis for the initiation, maintenance and termination of pregnancy in humans. Psychoneuroendocrinology 1988;13:155-70. DOI: 10.1016/0306-4530(88)90012-1'},{id:"B2",body:'Astle S, Slater DM, Thornton S. The involvement of progesterone in the onset of human labour. Eur J Obstet Gynecol Reprod Biol 2003;108:177-81. DOI: 10.1016/s0301-2115(02)00422-0'},{id:"B3",body:'Rosenfeld CR, Chen C, Roy T, Liu X. Estrogen selectively up-regulates eNOS and nNOS in reproductive arteries by transcriptional mechanisms. J Soc Gynecol Investig 2003;10: 205 – 15. 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1. Introduction
Eight out of the hundred reported herpesviruses, from the family herpesviridae (herpein meaning, “to creep”), cause lytic and latent infections in the humans. The human herpesviruses are classified into the alpha-, beta- and the gamma-herpesviruses, based on the range of hosts they infect. The alpha (α)-herpesviruses, involving the herpes Simplex Virus −1 (HSV-1), HSV-2 and the varicella zoster virus (VZV), are known to infect a broad range of hosts while having a short replication cycle in these hosts. The beta (β)-herpesviruses include the members, the human cytomegalovirus (HCMV) and the reseolo-human herpesvirus −6 and − 7, and infect a restricted range of hosts as compared to the α-herpesviruses while having a longer replication cycle within these hosts. The third group known as the gamma (γ)- herpesviruses, containing the Epstein–Barr virus (EBV) and the Kaposi’s sarcoma associated herpesvirus (KSHV), have the most restricted host range amongst the three sub-categories of human herpesviruses [1]. As reported for the year 2016, 13.2% of the global population aged 15 to 49 years were harboring HSV-2 within themselves, whereas about 66.6% amongst the 0 to 49 years aged individuals had HSV-1 infection [2]. Persons infected with HSV-2 are at 3 times to risk of infection with HIV compared to persons who are not infected with HSV-2 [3]. This may or may not be due to a biological process as implied, but behavioral and the specific populations are vulnerable to infections with both the viruses. Both HSV-1 and 2 have an envelope of lipid-bilayer encasing them and have a double-stranded DNA (~152 kb) as their genetic material. The 12 glycoproteins in the outer layer participate in the entry of the HSV into the cell. The viral genes are expressed in an orderly fashion with the immediate early (IE) genes expressed first, which encode the proteins for the regulation of the viral replication. This is followed by the expression of the early (E) genes, which encode for the enzymes involved in the replication process. Finally, the expression of the late (L) genes takes place, which encode for the structural proteins of HSV [4]. The completion of the replicative cycle results in the generation of assembled virions which are transported via the endoplasmic reticulum/Golgi cargo transport system to the cell membrane, where the virions are released by acquiring a part of the host’s cell membrane. HSV infection leads to pain and suffering, which although not always, may be lethal to the host. HSV-1 mainly causes the stromal keratitis in the eye whereas HSV-2 is responsible for genital lesions [4]. No vaccines against HSV are available for public use, although some are undergoing clinical trials. Therefore, drugs like Acyclovir, Valacyclovir and Famciclovir are the only therapeutic solutions available, which are associated with side-effects and limitations in bioavailability [5]. Thus, more suitable therapeutic agents, in terms of optimal bioavailability and diminished adverse effects, is the need of the hour.
MicroRNAs (miRNAs) on the other hand, are gaining a growing attention from the scientific community as the self-molecules which are the key regulators in infection and disease. These 20–24 nucleotides are non-protein coding RNAs which act post-transcriptionally to regulate the expression of the genes [6]. Since its discovery, miRNAs have found their significance in the diagnostics and therapeutics of diseases such as cancers, diabetes and infections of bacteria and viruses [7, 8, 9, 10, 11, 12, 13]. Thus, in this chapter, we have made an attempt to review the facts known about miRNAs are discuss their role in herpesvirus infection with our main focus on HSV infections.
2. Biogenesis of miRNAs
2.1 Canonical pathway for miRNA biosynthesis
The biological synthesis of miRNAs may be either from intragenic or intergenic sequences. Most of the intragenetically synthesized miRNAs are from introns whereas some are from exons of the protein coding genes. miRNAs are also synthesized from intergenic sequences which are independent miRNA genes and have their own, specific promoters. There are canonical as well as non-canonical pathways for miRNA genesis [14]. The canonical pathway for miRNA biogenesis marks the transcription of the primary miRNA (pri-miRNA) from the miRNA genes by RNA Polymerase II (RNA Pol II) in the nucleus. After the transcription the pri-miRNA, which can be as long as 1000 nucleotides in length, they are processed by a microprocessor complex consisting of an RNA-binding protein DGCR8 and an RNase III Drosha. Pri-miRNA methylation by methyltransferase-like 3 (METTL3) marks it for recognition by DGCR8 of the microprocessor complex [15]. DGCR8 recognizes the intersection of the flanking single-stranded (ss) RNA and the stem loop in the pri-miRNA hairpin-structure after which, the Drosha is recruited and involves in a cleavage process [16]. This processing forms the precursor miRNAs or pre-miRNAs (~80 nucleotides in length) having 2 nucleotide 3′ overhangs, which are transported from the nucleus to the cytosol by Expotin-5 (XPO-5)/ Ran-GTP complex. In the cytosol, the Ran GTPase- activating protein brings about the hydrolysis of GTP, changing the Ran conformation, thereby, releasing the pre-miRNA bound to the XPO5 [17]. After the release, the RNAse III endonuclease Dicer removes ~22 base pairs (bp) of the pre-miRNA terminal loop to form the mature miRNA duplex (Figure 1). This processing step of the miRNA allows them to be eligible for loading onto the Argonaute (Ago) complex of proteins which are the essential components of the RNA-induced Silencing Complex (RISC), therefore, the miRNAs mediate their action (Figure 1). The decision for the specific loading of a strand of miRNA duplex on the RISC complex is made on the basis of the thermodynamic stability of the two strands and is accompanied by ATP hydrolysis [18]. The strand with a lower 5′ stability or a 5’ Uracil is named as the guide strand (~22 nucleotides in length) and is loaded onto the Ago protein, while the strand not loaded onto Ago, named as the passenger strand, is cleaved by the slicer activity of the Ago and degraded by the ribonucleases [14, 19].
Figure 1.
Biogenesis of miRNAs: A. transcription of pri-miRNA from the miRNA gene by RNA pol II followed by B. Drosha/DGCR8 cleavage of the pri-miRNA to pre-miRNA. C. the pre-miRNA is then exported from the nucleus to the cytoplasm with the help of the Exportin 5 /ran GTP complex where D. dicer cleavage of the hairpin structure takes place. E. One of the strands of the miRNA duplex is loaded onto the RISC, via the ago protein which causes the F. repression of the gene expression by base complementarity-induced mRNA degradation or translation repression.
2.2 Non-canonical pathways for miRNA biosynthesis
While most of the miRNAs are generated via the canonical pathway, there are many which are synthesized by the non-canonical pathways. Although there may be many such non-canonical miRNA synthesis pathways, they use up different combinations of proteins that are participants of the canonical pathway. Primarily, there are two types of the non-canonical pathways, the Drosha/DGCR8 independent route and the Dicer independent route. Mitrons are an example of miRNAs synthesized by the Drosha/DGCR8 independent pathway, where the pre-miRNAs generated are similar to the Dicer substrates [20]. Here, Exponin-1 needs to transport the miRNA transcripts to the cytosol without Drosha processing it and allows a biased 3p strand loading onto Ago-2. On the other hand, the Dicer-independent pathway involves Drosha processing of the short hairpin RNA (shRNA) transcripts, but is too short to be cleaved by Dicer [21]. Hence, the entire pre-miRNA is loaded onto the Ago-2, which slices the 3p strand. Finally, the trimming from 3′-5′ of the 5p strand concludes the maturation of the miRNA [14, 22].
3. Role of miRNAs in HSV replication
miRNAs play a huge role in the crosstalk between the virus and the host. There are certain viral and cellular miRNAs that regulate the host responses to a viral infection as well as the progression of infection. Both the viral and the cellular miRNAs are capable of regulating the host and the viral mRNAs. Some of the miRNAs that have been identified to be involved during the HSV-1 infection have a direct or indirect impact on the viral replication. These cellular miRNAs may directly target the HSV genome or are manipulated by the HSV through the viral proteome/transcriptome [23]. HSV-1 infected HeLa cells have shown a downregulation of the miR-649 cellular miRNA that targets a ubiquitously expressed cytoplasmic protease, MALT-1, which activates the NF-κB signaling (Figure 2). Since NF-κB signaling inhibits HSV-1 replication, the downregulation of miR-649 elevates the expression of MALT-1, increasing the restriction on HSV-1 replication [24]. Similarly, another cellular miRNA which is involved in the suppression of HSV-1 replication is miR-101 (Figure 2). The HSV- viral immediate early protein ICP4 directly binds to the promoter of miR-101 to increase the expression of miR-101 in the infected cells thereby decreasing the expression levels of its target GRSP1, which is a scaffolding protein that may be involved in the polarization of epithelial cells. GRSP1 directly bind to the HSV-1 p40 and increases the replication of HSV-1. With enhanced suppression of GRSP1, the replication of HSV-1 is hindered. Although it seems surprising that HSV auto-downregulates its replication, it may be a necessary step for the virus to prevent host cell death due to lysis, therefore, maintaining a permissive milieu for virus harboring and replication within the cells [25]. Also, miR-101 can target ATP5B, a subunit of the ATP synthase, to restrict the HSV-1 replication [26]. These studies depict that a single miRNA such as miR-101 could regulate multiple targets to restrict the viral replication. In a study conducted by Shabani et al., a macrophage miR-7704, was capable of reducing the HSV-1 replication in HeLa cells [27]. Another cellular miRNA, miR-23a which targets the Interferon regulatory factor-1 (IRF-1), involved in innate antiviral immunity, is upregulated, so as to escape the host immune responses [28]. Also, a direct suppressor of IRF-1, miR-373, enhances HSV-1 replication by supressing the interferon stimulatory gene responses (Figure 2) [29]. Increased expressions of miR-155, a miRNA which could epigenetically increase the transcription of the serine/arginine-rich splicing factor 2 (SRSF2), enhances the HSV-1 replication, due to SRSF2- mediated transcriptional activation of the HSV-1 genes (Figure 2) [30]. Some HSV-1 viral miRNAs have also been studied that regulate the virus’s replication. HSV-miR-H6, a viral miRNA which is generated profusely during HSV-1 infections, reduces HSV-1 replication by downregulating the viral protein ICP4 (Figure 2) [31]. Also, H-27 targets KLHL24 which is a transcriptional repressor (Figure 2). Therefore, increase in H-27 expression does not allow KLHL24 to suppress the HSV-1 immediate early and early gene expression, thus, promoting HSV-1 replication [23, 32].
Figure 2.
miRNAs in HSV replication: The figure describes the mode of action of the various cellular miRNAs (green) and the viral miRNAs (blue) that regulate the HSV replication. While the cellular miRNAs, miR-649, −101, −23a, −373 and the viral miRNA, miR-H6 block the HSV replication, the cellular miRNA, miR-155 and the viral miRNA, H-27 promote the HSV viral replication. Both the viral and the cellular miRNAs regulate the host as well as the viral gene expression to modify the replication process either as a host response tying to fight the infection or to establish the infection within the host. Pointed arrowheads indicate progression of an event while blunt arrowheads indicate blockade of an event.
4. miRNAs in acute HSV infection and latency
Encephalitis due to acute HSV-1 or − 2 infection could arise as a direct effect of the HSV invasion of the host or due to the heightened host responses to the virus which causes host damage in the process of virus destruction. Although the incidence of Herpes Simplex Encephalitis (HSE) cases is low, 20% of those affected face neurological after-effects [23]. The inflammation associated with encephalitis often involve the miRNAs, which is also the situation in HSE. miRNAs also contribute to the susceptibility of the cells to HSV infection. This may be the reason for the discovery of a number of cellular miRNAs in HSE. miRNAs miR-155, miR-146a and miR-15b were found to be upregulated in the mouse brain post-HSE [33] and have been associated with neuroinflammation (Figure 3) [34]. HSV-1 encoded miR-H28 and miR-H29 were identified to be expressed late during the infection and are exported out of the infected cells in exosomes, thus indicating a role of these miRNAs in viral spread [35]. Also, miR-200 family and miR-182 are the miRNAs identified to be involved in HSE as they target Syndecan-2 (sdc2) which contributes to the biosynthesis of the heparan sulphate required for the attachment and entry of HSV into the cells. Therefore, downregulation of sdc2 by miRNAs is a strategy maneuvered by the host to resist the spread of the virus [33]. This also depicts that mutations in the miRNA sequence or the mRNA target are key players in varied susceptibility to the HSV infection of the central nervous system.
Figure 3.
miRNAs in HSV latency: Majorly, the LAT-associated v-miRNAs participate in the induction, establishment and maintenance of latency of the HSV in the cells. HSV-miR-I and miR-II suppress the ICP34.5 expression to restrict HSV replication and promotion of the HSV latency. HSV-miR-H2 and miR-III inhibit the ICP0 expression to suppress the HSV replication. HSV-miR-LAT inhibits apoptosis to allow the infected cell and the virus to survive and establish a latent infection. There are two cellular miRNAs that contribute to the latency. miR-138 promotes latency by preventing ICP0-triggered viral replication whereas miR-155 contribute to the maintenance of latency via the induction of the CD8+ responses.
The opposite of excessive HSV pathogenesis is HSV latency, a phase of HSV infection characterized by minimum genome replication. HSV uses neurons as the hideaway for escaping the spotlight for the immune responses while sheltering itself within the host. Since the discovery of HSV- miRNAs in 2006, many miRNAs have been identified to participate in the different stages of viral latency [36] miR-LAT (Latency associated transcript), a miRNA generated from the exon 1 of the HSV1-LAT gene, is responsible for the TGF-β mediated anti-apoptotic effects on the cells during latency. HSV-miR-H2 has been found to suppress the immediate early protein ICP0, therefore, inhibiting the replication to promote HSV latency (Figure 3) [37]. On the other hand, HSV2-miR-H6, a miRNA associated with HSV2-LAT, contributes to the reactivation of the virus from latency [38]. Mutation studies on both these miRNAs confirm their effects. miR-I, is another HSV2-LAT associated miRNA which reduces the expression of ICP34.5, a neurovirulence factor, to establish latency in the dorsal root ganglia [39]. A similar study by the same group identified miR-II and miR-III miRNAs from the HSV2-LAT, with miR-II targeting ICP34.5 and miR-III targeting ICP0, to maintain latency (Figure 3) [40]. Furthermore, the cellular miRNAs also engage in the events of HSV latency. miR-155 is involved in the maintenance of latency via the elicitation of CD8 responses [41]. Similarly, enhanced expression of miR-138 in the neurons, to target ICP0 for suppression (Figure 3), is crucial in maintaining the HSV-1 latency and survival of the hosts [42]. The crosstalk between the viral/cellular miRNAs, amongst themselves, and with the host transcriptome decides for the maintenance of latency which may be for the lifetime, or trigger the reactivation of the virus.
5. Role of miRNAs in the immunological events of HSV infection
Ocular infection by HSV-1 may lead to chronic inflammation resulting in lesions of stromal keratitis (SK). The immunological events underlying the development of SK involve organized T-helper 1 (Th1) and T-helper-17 (Th17) cells, which produce IFN-γ and IL-17, respectively [43, 44]. Also, the involvement of the regulatory T cells (Treg) guides the exacerbation or abatement of the keratitis [45, 46] miRNAs also regulate the development, activation, function and recruitment of the Th and the Treg cells [47]. A pro-inflammatory miRNA, miR-155 is known to be upregulated during SK and leads to the enhancement of the Th1 and Th17 responses and helps promoting the keratitis. Antagomir nanoparticles containing the anti-miR-155 sequences have been shown to downregulate miR-155 expression and suppress SK [48]. Also, miR-132 was found to be upregulated during SK, which helps in the advancement of angiogenesis via upregulation of the vascular endothelial growth factor (VEGF) by directly targeting a negative regulator of VEGF, a Ras-GTP inhibitor [49]. The Toll-like receptor (TLR) pathway is an integral innate immune response pathway that is altered in almost all infection scenarios. Similarly, the genes associated with the TLR pathway are modulated post-HSV-2 infection by the miRNAs, miR-124, miR-150, miR-342-5p, miR-1245b-5p, miR-1245b-3p, and miR-592 [50]. Speaking of the innate immune responses, type I Interferon (IFN) signal transduction plays a crucial role in curbing viral replication. Thus, for the virus to establish a progressive infection, it must manipulate the host machinery to overcome the IFN combat. So far, in case of HSV-1, miR-221 is manipulated by HSV-1 to suppress the IFN-β production and effector functions [51]. The major innate immune response involved immediately after the HSV infection is the series of events resulting in acute inflammation, which is essential for virus clearance. This also implies that the infiltrates need to be resolved and the cell debris need to be cleared off so as to maintain the immunological homeostasis of the host, preventing a chronic inflammation that could be lethal [52]. Certain pro-resolving mediators (SPMs) function to resolve the acute inflammatory state and may engage a few miRNAs to do so. The binding of Resolvin (RvD1), a SPM, to its receptor upregulates the miRNAs miR-21, miR-146b, miR-219, and downregulates miR-208a [53, 54]. The target mRNA of miR-219 is the transcript of the gene encoding the 5-lipoxygenase enzyme that leads to the decreased production of leukotriene B4 and increased production of the SPMs. miR-146b suppresses the expressions of IL-8 and RANTES, which are the leucocyte-recruiting chemokines at the inflamed regions [54]. miR-146a is also pro-inflammatory in nature and have been shown to trigger the arachidonic acid-mediated, overproduction of IL-1β, to induce an Alzheimer’s-like neuropathological condition in the brain. Since it can directly suppress the complement factor H, it is considered as one of the mechanisms of complement evasion by HSV-1 [55]. Another miRNA upregulated as a result of RvD1 binding is miR-21 which contributes to the establishment of an anti-inflammatory milieu by increasing the production of IL-10 when the resolution of inflammation is vital [56, 57]. Contradictorily, miR-208a, which decreases the IL-10 production and enhances the NFκB activation to prolong the inflammatory events, was itself constrained [54]. It has also been noted that miRNAs can function in a cell/tissue-specific manner. miR-4661 is one such miRNA that promotes acute inflammation in the neutrophils, whereas mediates the cessation of the inflammatory responses in the monocytes and the macrophages via the augmented production of SPMs. It also polarizes the macrophages towards the resolution of inflammation [58]. HSV-1 miR-H8 reduces natural killer (NK) cell- dependent killing of the virus-infected cells by the suppression of the glycosylphosphatidylinositol gene expression [59]. HSV-1 viral miR-H28 induces the production of IFN-γ also to restrict the spread of HSV-1 between cells while not affecting the viral replication, so that optimal transmission between individuals take place [60].
6. Other herpesviridae viral miRNAs
The herpes simplex virus 1 and 2 discussed mainly in this chapter are also termed as human herpesvirus (HHV)-1 and 2. The other members of the herpesviridae family of viruses include the Varicella zoster virus (VZV) or HHV-3, the Epstein Barr virus (EBV) or HHV-4, the human cytomegalovirus (HCMV) or HHV-5, the Roseoloviruses HHV-6 and HHV-7, and the Kaposi’s sarcoma-associated herpesvirus (KSHV) or HHV-8 [61]. A common characteristic of the herpesviruses is that all the members are capable of establishing latent infections in their hosts and reactivate when the immune system has been compromised. Herpesvirus reactivation brings about changes in the host signaling pathways with the help of alterations in the miRNA expression [62]. VZV is a neurotropic virus that causes chickenpox in humans. Although there are not many reports on VZV v-miRNAs, nearly 20 miRNAs have been predicted from the VZV genome and some of these miRNAs have been shown to be involved in viral replication [63, 64]. EBV, the first human oncovirus reported to encode viral miRNAs and cause various cancers such as nasopharyngeal carcinoma and Burkitt’s lymphoma, encodes 44 miRNAs. The EBV miRNAs target the viral as well as the host mRNAs to regulate carcinogenesis and cellular transformation of the EBV-associated cancers [65]. HCMV, which allows extensive replication in the endothelial as well as the epithelial cells and has a large dsDNA genome of 230 bp, encodes 22 miRNAs [66, 67]. KSHV, a gamma herpesvirus and the causative agent of Kaposi’s sarcoma, encodes 25 miRNAs. The family also contains HHV-6 and HHV-7, which are the lesser explored members. A single miRNA, miR-U86, encoded by HHV-6A has been reported to target the expression of the U86 gene which is an IE gene of HHV-6A [68]. Therefore, apart from HSV-1 and HSV-2, the other members of the herpesviridae family also encode a number of miRNAs to regulate their infection cycles in the host. Owing to similarities amongst them, investigations pertaining to one will provide insights regarding the other. Here, we discuss some of the miRNA effector functions that are employed during other herpesvirus infections.
6.1 The human cytomegalovirus (HCMV) miRNAs
The HCMV have co-evolved with their hosts and encoding miRNAs that are capable regulators of cell cycle progression, viral gene expression, apoptosis and host immune response evasion (Figure 4). In order to maintain the latent infection, the virus attempts to maintain the hematopoietic progenitor cells (HPCs) in the dormant state. EGR-1 (Early growth response gene-1) is critical in maintenance of the HPC quiescence. miR-US22 is a HCMV miRNA that is expressed during the early infection stages or reactivation to restrict the proliferation of the HPCs. It does so by targeting the host transcription factor, EGR-1, so that the HCMV can overtake the host replication machinery for its own replication. Since viral replication is close to negligible during latency, the HCMV miR-US22 is not expressed during this state [69]. Another miRNA mechanism to limit cell proliferation during latency is the suppression of the RhoA, a regulator of the actin dynamics. miR-US25–1 targets the RhoA GTPase to disable mitosis in the cells [66, 67]. The lytic and latent infections are characterized by the abundant expression of the miRNAs, miR-US25–1, miR-UL112-3p, and miR-UL22A. Although most of the HCMV miRNAs are detected during the first 4 hours of infection, miR-UL22A, miR-UL112-3p and miR-UL148D continue to be detected post-IE infection. miR-UL112-3p targets the UL123 viral mRNA that codes for IE72 which is actively involved in viral replication and cell lysis [70] miR-UL148D targets the IE response 5 transcript to indirectly regulate the expression of the viral IE genes through the signaling transduction events induced by Cyclin-dependent kinase 1 (CDK-1) in order to promote latent HCMV infections [71]. The FOXO transcription factors are the facilitators of both mitochondria-dependent and -independent pathways for the induction of apoptosis in cells [72] miR-US5–1 and miR-UL112-3p of HCMV have known to target a member of the FOXO family, FOXO3a [73]. The mechanism involves a downregulation of FOXO3a expression such that its pro-apoptotic functions are limited and binding to the promoter of Bcl-2-like protein 11 (Bim) is restricted. In profusely HCMV replicating cells, the IKK expression was directly constrained by the miR-US5–1 and miR-UL112-3p miRNAs of HCMV, such that production of the pro-inflammatory cytokines, IL-6 and RANTES via the NF-κB pathway was considerably suppressed [74] miR-UL148D directly targets the RANTES transcript to suppress its pro-inflammatory functions [75]. Also, miRUL112-3p directly targets MICB, an MHC I-related chain B, to indirectly repress the NK-cell killing activity so as to protect the infected cells from destruction during the lytic and preferably also during the latent HCMV infections [66, 67, 76].
Figure 4.
miRNAs in other herpesvirus infections: The figure summarizes the involvement of the various miRNAs in the different events of other herpesvirus infection. Here, we have taken the example of two herpesviruses, HCMV (navy blue) and KSHV (magenta) to show the extent of v-miRNA involvement during the viral pathogenesis. Mostly, the viral miRNAs involved in replication, latency, cell survival and immune modulation have been mentioned in the figure and are the ones widely explored.
KSHV miRNAs regulate the viral mRNAs directly as well as indirectly via the regulation of the cellular mRNAs (Figure 4). Certain viral miRNAs participate to establish latency in the KSHV-infected cells. miR-K7 and miR-K9–5p target the KSHV RTA protein, which acts as a switch between the lytic and latency cycles [77, 78]. Also, miR-K11 and miR-K3 function to maintain latency by indirectly suppressing the RTA transcript [79, 80, 81]. Another latency-inducing miRNA is the miR-K4-5p which inhibits the retinoblastoma-like protein-2 (RBl2) expression due to which the DNMT1 (methylation enzyme) expression increases. Methylation of the RTA promoter by DNMT1 suppresses RTA expression, inducing latency in the cells [79, 81]. Angiogenesis is an important event in the KSHV infection as it allows the spread of the latency-induced malignancies. GRK2 which regulates the AKT/CXCR2 pathway to establish a reciprocity between viral replication and induction of angiogenesis, is targeted by miR-K3 to decrease viral replication and induce angiogenesis, thus establishing latency [82]. Contradictorily, BCLAF1, Bcl 2-associated factor-1, is the common target for miR-K5, miR-K9 and miR-K10a/b and has been known to trigger the lytic infection cycle [83] miR-K5 and K9 also suppress the TLR-mediated production of the inflammatory cytokines IL-6, IL-8 and IL-1α by directing interfering with the intermediates, MyD88 and IRAK-1, respectively [84, 85]. The KSHV miRNAs also attempt to inhibit apoptosis and promote cell survival, which is crucial for both malignancy and latency. Therefore, miR-K1, -K3 and -K4 inhibit apoptosis by directly targeting the Caspase-3 protease [86] miR-K10, the viral orthologue of hsa-miR-142-3p, targets TGF-β to promote cell survival and cellular transformation [87, 88] miR-K10a is also the negative regulator of the TWEAK receptor, which is the receptor for the TNF-like weak inducer of apoptosis, thereby, inhibiting apoptosis as well as downregulating the production of IL-8 and MCP-1 to contribute to the KS progression [89] miR-K1 also promotes cell cycle progression by inhibiting p21 [90]. Another target for miR-K1, IκBα, which usually retains NF-κB in the cytoplasm by blocking the nuclear localization signals, is constrained to promote latency and survival of the transformed cells [91]. Activation of NF-κB also inhibits the Warburg effect leading to the declined expressions of GLUT-1 and GLUT-3, suggesting the significance of the metabolic regulation for the proliferation of the KS cells [92]. Just as miR-155 have been considered as the regulatory epicenter of various cancers and viral infections, the KSHV miRNA, miR-K11 mimics some of the functions of this cellular miRNA. miR-K11 blocks the C/EBPβ resulting in the enhanced, IL-6-mediated proliferation of the B cells [93]. It also targets JARID2 leading to increased B cell transformation [94]. Moreover, miR-K11 also inhibits the IFN type I signaling by directly targeting IKKε mRNA [95, 96]. Thus, the generation of cellular miRNA orthologues by the herpesviruses is clearly evident of its co-evolution with its host, such that it diverts the cellular machinery towards its own viral processes while hiding itself efficiently from the host responses.
7. miRNAs as potential biomarkers in herpesvirus infections
With as many miRNAs that are expressed during each of the herpesvirus infections, the recognition of certain miRNAs are biomarkers for these infections is promising. There are a number of reasons that back the concept of miRNA biomarkers in human infections. The distinct pathophysiological events occurring during the infection is reflected in the miRNA expression patterns. For example, where miR-649 is considerably downregulated in HSV-1 infected cells as compared to the uninfected cells to mark the overwhelming participation of NF-κB is fighting the infection, there are certain miRNAs exclusively generated by the HSV (miR-H6, -H27 etc.). miRNAs are also the biomarkers of the HSV infection status within the host as certain miRNAs are specific to the lytic phase (miR-H1) whereas some are specifically expressed during the latency phase (miR-H2–6). miRNAs are easily available for detection in the body fluids such as blood, serum and human dental pulps [97, 98] and so are the v-miRNAs of the herpesviridae family members [99]. Although there are a few ongoing clinical studies on miRNAs biomarkers in cancer, the reports on EBV-related cancer miRNAs also being detected in the blood and urine, will boost the EBV research in the same direction [100]. Furthermore, the molecular techniques used for the miRNA detection, such as, the real-time PCR array, microarray profiling and the next-generation sequencing techniques are popular and well established in case of herpesvirus infections as well [101, 102, 103, 104]. One of the greatest advantages of using miRNAs as biomarkers is their sustained expressions in vivo as compared to the mRNAs. This is because of the presence of exosomes which enclose the miRNAs. Moreover, the miRNAs released extracellularly are bound to the Ago proteins. These mechanisms protect the miRNAs against degradation by the nucleases [35, 105, 106]. Whether v-miRNAs or cellular miRNAs are better biomarker candidates might be debatable. However, an important consideration in this context is that v-miRNAs are virus-specific whereas host miRNAs are not exclusive for a virus infection. For example, miR-155, which is crucial in HSV-1 latency is also involved in pro-inflammatory functions in other diseases such as cancer, asthma, arthritis, Cystic fibrosis and also recently reported in other viral infections, such as that of the Sars-CoV-2 [41, 107, 108]. Therefore, a panel of host and viral miRNA combinations may serve as an appropriate biomarker in case of each of the herpesvirus infection.
8. Therapeutic considerations of miRNAs in herpesvirus infection
miRNAs can also be referred to as the endogenous post-transcriptional gene regulators and have a special advantage over drugs. miRNAs are self-molecules and hence are safer than any of the synthetic or natural compounds used as therapeutics against the infections. Another feature of miRNAs that make them interesting candidates for therapeutic considerations is their ability to regulate more that one gene expression, and inversely, the expression of a single gene can be modulated by more than one miRNA. Being the regulators of gene expression, modification of the miRNAs is an approach for changing the course of an infection or a disease. There are two ways by which the miRNA expression may be modified. One of modifications include reintroduction of the miRNA expressions by the use of specific miRNA mimics, while the second is to block the infection-induced/modified miRNA expression by the use of the specific-miRNA inhibitors [23]. The use of miRNA mimics and inhibitors have been trending in the field of research on infectious diseases since the successful progression of miRavisen through the clinical trials to be established as therapeutics against the Hepatitis C virus [109] miRavisen is a miRNA inhibitor of miR-122, a miRNA which increases the HCV viral replication [110, 111]. Similarly, inhibitors of miR-373 or HSV-miR-H27 can be administered as therapeutics to decrease the HSV viral load in the hosts. There have also been studies where mimics of miRNAs have proved to be useful in restricting viral replication. Recently, a study identifying the significance of miR-29b mimics have been reported to decrease the Rotavirus infection considerably [112]. Likewise, mimics of miR-7704 and miR-101 could be encouraged in the HSV therapeutic research. Furthermore, the reported miRNA research could be compiled to develop therapeutic formulations involving combinations of mimics and inhibitors to synergistically suppress the HSV infection in the host. However, miRNAs, like any other therapeutics, face the challenges of target-specific delivery and off-target effects. These challenges are also being addressed by the researchers with the synthesis of appropriate miRNA-loaded nanoparticles which ensures on-site targeted delivery and optimal bioavailability while maximally reducing the off-target effects [6]. All-in-all, the potentiality of miRNAs as therapeutic agents against viral infections is being explored explicitly, also implying that their clinical applications in herpesvirus infections is inevitable.
9. Conclusion
Elucidation of miRNAs have emerged as a promising field of research due to the capability of the miRNAs to be easily manipulated to alleviate an infection. The fact that a single miRNA can target more than one gene expression (viral, cellular, or both) to suppress the viral infection is equally fascinating and efficient. The significance of miRNAs as biomarkers and therapeutic agents in infection makes them acceptable to the researchers. All the more, the commercially available mimics and inhibitors of the miRNAs makes the research pertaining to them affordable. However, miRNAs face the challenges of specific, on-site delivery, long-term miRNA stability and off-target consequences, and yet, have been FDA-approved under the small molecule therapeutics category. The challenges of targeted delivery and optimum bioavailability is met with the miRNA-loaded nanoparticles, which diminish the off-target effects as well. Thus, with miRNAs finding their utility into a variety of applications, expansion of the miRNA investigations, both in basic and applied research, is evident.
\n',keywords:"Herpesviridae, HSV, miRNA, miRNA biogenesis, HHV, KSHV",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78821.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78821.xml",downloadPdfUrl:"/chapter/pdf-download/78821",previewPdfUrl:"/chapter/pdf-preview/78821",totalDownloads:126,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 20th 2021",dateReviewed:"September 9th 2021",datePrePublished:"November 15th 2021",datePublished:"January 12th 2022",dateFinished:"September 30th 2021",readingETA:"0",abstract:"MicroRNAs (miRNAs), first discovered in the year 1993 in the nematode C. elegans, are small, approximately 22-nucleotide-long, non-coding RNAs that regulate gene expression. Cellular miRNAs have been implicated in the control of many biological processes, and their dysregulation is associated with different diseases. They can be significantly up/downregulated upon infection or disease, serving as excellent biomarkers and therapeutic targets. Several human DNA viruses, including many herpesviruses, have now been reported to encode viral miRNAs. There are a variety of possible interactions and mechanisms of viral microRNAs (vmiRNAs) which are yet to be remains obscure. Viral miRNAs can function as orthologs of cellular miRNAs and regulate their expression. Additionally, viruses have also developed vmiRNA mechanisms to avoid being targeted by the host miRNAs. Herpes Simplex Viruses (HSV-1 & HSV-2) cause genital and oral herpes, establishing lifelong latent infections in their hosts, and it is one of the most prevalent sexually transmitted infections (STIs) worldwide. vmiRNAs play essential roles in Herpesvirus biology. In this chapter, we will discuss the current knowledge about miRNAs and their role in different stages of Herpesvirus infection. It will also elaborate the biomarkers, therapeutic potential of these molecules, and the prospective areas of future research.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78821",risUrl:"/chapter/ris/78821",signatures:"Anwesha Banerjee and Anupam Mukherjee",book:{id:"10470",type:"book",title:"Current Perspectives on Viral Disease Outbreaks",subtitle:"Epidemiology, Detection and Control",fullTitle:"Current Perspectives on Viral Disease Outbreaks - Epidemiology, Detection and Control",slug:"current-perspectives-on-viral-disease-outbreaks-epidemiology-detection-and-control",publishedDate:"January 12th 2022",bookSignature:"David Claborn",coverURL:"https://cdn.intechopen.com/books/images_new/10470.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83881-911-8",printIsbn:"978-1-83881-910-1",pdfIsbn:"978-1-83881-915-6",isAvailableForWebshopOrdering:!0,editors:[{id:"169536",title:"Dr.",name:"David",middleName:null,surname:"Claborn",slug:"david-claborn",fullName:"David Claborn"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"357335",title:"Dr.",name:"Anupam",middleName:null,surname:"Mukherjee",fullName:"Anupam Mukherjee",slug:"anupam-mukherjee",email:"amukherjee@nariindia.org",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"National AIDS Research Institute",institutionURL:null,country:{name:"India"}}},{id:"416431",title:"Ms.",name:"Anwesha",middleName:null,surname:"Banerjee",fullName:"Anwesha Banerjee",slug:"anwesha-banerjee",email:"banerjee.anwesha1991@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"National AIDS Research Institute",institutionURL:null,country:{name:"India"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Biogenesis of miRNAs",level:"1"},{id:"sec_2_2",title:"2.1 Canonical pathway for miRNA biosynthesis",level:"2"},{id:"sec_3_2",title:"2.2 Non-canonical pathways for miRNA biosynthesis",level:"2"},{id:"sec_5",title:"3. Role of miRNAs in HSV replication",level:"1"},{id:"sec_6",title:"4. miRNAs in acute HSV infection and latency",level:"1"},{id:"sec_7",title:"5. Role of miRNAs in the immunological events of HSV infection",level:"1"},{id:"sec_8",title:"6. Other herpesviridae viral miRNAs",level:"1"},{id:"sec_8_2",title:"6.1 The human cytomegalovirus (HCMV) miRNAs",level:"2"},{id:"sec_9_2",title:"6.2 Kaposi’s sarcoma (KS)- associated herpesvirus (KSHV) miRNAs",level:"2"},{id:"sec_11",title:"7. miRNAs as potential biomarkers in herpesvirus infections",level:"1"},{id:"sec_12",title:"8. Therapeutic considerations of miRNAs in herpesvirus infection",level:"1"},{id:"sec_13",title:"9. 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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Indexing and listing across major repositories, see details ...
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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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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He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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Samim Al Azad and Slimane Ed-dafali",hash:"86a6d33cf601587e591064ce92effc02",volumeInSeries:1,fullTitle:"Leadership in a Changing World - A Multidimensional Perspective",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038UqSfQAK/Profile_Picture_2022-05-13T10:39:03.jpg",institutionString:"Université Laval",institution:{name:"Université Laval",institutionURL:null,country:{name:"Canada"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Business and Management",value:86,count:1}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine"},{id:"8",title:"Bioinspired Technology and Biomechanics",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. 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Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/98039",hash:"",query:{},params:{id:"98039"},fullPath:"/profiles/98039",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()