Summary of studies of extraction of flavonoids from different sources.
\r\n\tThe book will aim to cover also the synthesis and optical properties of noble metal nanostructures, patterned surfaces, continuous or grated surfaces, and devices. This book intends to provide the reader with a comprehensive overview of the current state-of-the-art in plasmonic microscopy, surface-enhanced spectroscopic properties, such as Raman scattering or fluorescence, as well developments in techniques such as surface plasmon resonance and near-field scanning optical microscopy but also data transmission, plasmonic light modulators, and optoplasmonic networks.
",isbn:"978-1-80356-003-8",printIsbn:"978-1-80356-002-1",pdfIsbn:"978-1-80356-004-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"15d44e3a7898842276a9a9da9863a59d",bookSignature:"Dr. Patrick Steglich",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11147.jpg",keywords:"Biosensors, Surface Plasmon Resonance, Optoplasmonic Networks, Plasmonic Communication, Fabrication Methods, Device Simulation, Device Optimization, Surface Plasmon Resonance, Plasmonic Microscopy, Phonon-Plasmon Interaction, Physical Background, Mathematical Background",numberOfDownloads:14,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 19th 2021",dateEndSecondStepPublish:"February 25th 2022",dateEndThirdStepPublish:"April 26th 2022",dateEndFourthStepPublish:"July 15th 2022",dateEndFifthStepPublish:"September 13th 2022",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A senior researcher in photonics at IHP - Leibniz Institute for Innovations in Microelectronics, book author, lecturer at Technical Unversity of Applied Sciences Wildau, and holder of three registered patents.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"223128",title:"Dr.",name:"Patrick",middleName:null,surname:"Steglich",slug:"patrick-steglich",fullName:"Patrick Steglich",profilePictureURL:"https://mts.intechopen.com/storage/users/223128/images/system/223128.jpeg",biography:"Patrick Steglich is a research associate at the IHP - Leibniz-Institut für innovative Mikroelektronik, Germany, and lecturer for photonics and optical technologies at the Technical University of Applied Sciences Wildau, Germany. He obtained a master's degree in Photonics from the Technical University of Applied Sciences Wildau in 2013. In 2017, he received his PhD in Industrial Engineering from the Università degli Studi di Roma 'Tor Vergata” for his work in the field of integrated photonics for communication and sensing. His research focuses on emerging photonic devices and waveguide concepts for telecommunication and sensing applications.",institutionString:"Technical University of Applied Sciences Wildau",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:[{id:"81630",title:"Infrared Nano-Focusing by a Novel Plasmonic Bundt Optenna",slug:"infrared-nano-focusing-by-a-novel-plasmonic-bundt-optenna",totalDownloads:15,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444315",firstName:"Karla",lastName:"Skuliber",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/444315/images/20013_n.jpg",email:"karla@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"67850",title:"Implantation and the Fetal Health",doi:"10.5772/intechopen.87016",slug:"implantation-and-the-fetal-health",body:'\nMost of the fetal and maternal complications become apparent with advancing gestation. However, since very important complications that occur later in pregnancy can be predicted in the first trimester, the focus has been set on the evaluations in early pregnancy, thus inverting the pyramid of prenatal care. Although vast majority of early screening tests have been developed and employed, the outcome of pregnancies with the major obstetric syndromes still fails to be significantly improved. The changes etiologically and pathophysiologically associated with disturbed placentation and responsible for the perinatal mortality and morbidity should be sought even earlier, in the preimplantation period, in relation between the embryo and the endometrium.
\nThe idea of inverted pyramid of prenatal care has emerged for the purpose of prediction and prevention and then early detection and treatment of health disorders of the fetus. By applying this principle, a number of disorders could be prevented or treated with better outcome: fetal aneuploidy and anomalies, miscarriage, stillbirth, preterm delivery, preterm premature rupture of membranes, preeclampsia, and intrauterine growth restriction [1].
\nIn recent years, screening for aneuploidies during the first trimester has reached effectiveness of over 90% in identifying the most common aneuploidies by a combination of maternal age, fetal nuchal translucency, as well as analysis of free beta-hCG and pregnancy-associated plasma protein A (PAPP-A) [2]. Effectiveness of screening for potential aneuploidies was further augmented with the introduction of the noninvasive prenatal testing using maternal plasma cell-free (cf) DNA, as a secondary test in those patients already regarded as being at high risk. The detection rate of major aneuploidies with this test is up to 99. 3%, with false positive rate of 0. 11% [3].
\nThe development of sonography and MRI diagnostics has led to a growing number of early detected anomalies. A large number of these anomalies can be detected already at 11–14 weeks, while a number can only be found at a later gestation [4]. The prenatal detection rate for the major anomalies is around 68% (varying from 33 to 96%) [5, 6].
\nFirst trimester screening often focuses on fetal aneuploidy and major structural anomalies. However, certain maternal characteristics, such as the age and body mass index (BMI), have shown to be very informative, with regard to the predicting miscarriage and stillbirth. The risk of preterm delivery is determined by algorithms that combine these results of the first trimester screening for aneuploidy, increased nuchal translucency, the abnormal ductus venosus flow, and low level of PAPP-A, with the characteristics of the mother [7, 8, 9]. Such example is the information on the length of the cervical canal from 11- to 13-week gestation [9, 10]. The risk of spontaneous preterm delivery is associated with cervical shortening in the second trimester, as well as in the first trimester. Combining this parameter with fetal aneuploidy analyses and major structural anomaly results is likely to be used in the future to select a high-risk group that may benefit from close follow-up.
\nAnother example is the screening for the development of early preeclampsia (PE), based on the combination of maternal risk factors, mean arterial pressure, maternal serum PAPP-A, uterine artery Doppler, and placental growth factor. This algorithm has a 95% detection rate for a false-positive rate of 10% [11, 12]. Also, different angiogenesis-related biomarkers; antiangiogenic proteins, like soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin; or proangiogenic proteins, placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) have been pointed out by a number of authors [10]. The placental protein-13 and other markers, disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin A, and other microelements or antioxidants, in isolation or in combination, were evaluated in order to predict complications of pregnancy [13, 14, 15]
The detection of the small for gestational age (SGA) fetuses could be predicted by algorithms with the combination of maternal characteristics, mean arterial pressure, uterine artery Doppler, and the measurement of various placental products in maternal blood at 11–13 weeks, at a false-positive rate of 10%, about 75% of pregnancies without preeclampsia delivering SGA neonates before 37 weeks and 45% of those delivering at term [17]. Screening for macrosomia by a combination of maternal characteristics and obstetric history with fetal NT and maternal serum- free ß-hCG and PAPP-A at 11–13 weeks could potentially identify, at a false-positive rate of 10%, about 35% of women who deliver macrosomic neonates [18].
\nDespite the introduction of the vast early pregnancy screening tests, there is still a very slight decrease or even increase in the rate of preterm birth and almost a constant rate of miscarriage, stillbirth, preeclampsia, and SGA [19, 20, 21, 22, 23]. Except for hereditary and structural disorders of the fetus, other disorders are etiologically and pathophysiologically associated with disturbed placentation and responsible for the perinatal mortality and morbidity [24].
\nThe reasons why the modern medicine still fails to significantly improve the outcome of pregnancy with the major obstetric syndromes should be sought in the earlier period of pregnancy, even before the conception, and on another subcellular level (Personal communication Dudenhausen, Tirana 2015). Because the consequence of these disturbances is seen in dysfunctional placentation, their sources must be searched before the time of implantation. This means that the changes that lead to the insufficient implantation should be sought in the preimplantation period, in relation between the embryo and the endometrium.
\nThe onset and progression of pregnancy require the coordinated implantation of the embryo and trophoblast invasion into the receptive maternal decidua, followed by proper remodeling of the spiral arteries. Proliferation, migration, and invasion of trophoblastic cells into the maternal endometrium are the essential steps. If any of these steps fails to complete properly because of the endometrial dysfunction, the consequences would be the basis for development of obstetric complications.
\nThe implanting embryo physically establishes connections with the mother through the endometrium, by a fine-tuned and synchronized crosstalk necessary to support the feto-placental development and health throughout gestation [25]. Early alterations of endometrial physiology can affect the development of the conceptus and the success of pregnancy. The overall status of maternal health is reflecting on the endometrium. If we agree that the optimally prepared mucous membranes (either endogenously, by its own sex hormone or by exogenous regimes) are one of the preconditions for the successful implantation, then the modification of its preparation could influence the occurrence of disorders in later pregnancy and after the birth of the child.
\nSeveral studies have shown that preimplantation embryos are sensitive to environmental conditions in which it develops, either in vitro or in vivo, for example, in response to culture conditions or maternal diet [26]. Those conditions can affect future growth and developmental potential, both pre- and postnatally. Recent findings have demonstrated that perturbations of the maternal physiology during the peri-conceptional period (e.g., maternal diet) have impact both on preimplantation phenotype and long-term development and could lead to impaired health during adulthood [26]. Emerging evidence suggests the metabolic status of the mother may “program” the offspring’s long-term risk of metabolic disease [27].
\nModifications of preimplantation embryo conditions, using assisted reproductive technologies (ARTs) or somatic cell nuclear transfer (SCNT), have been associated with developmental abnormalities and postnatal consequences such as the large offspring syndrome (LOS) in animals [28, 29, 30]. Early alterations of the maternal or embryo environment may affect the quality of the embryo-endometrium crosstalk that further leads to pregnancy failure or postnatal detrimental consequences.
\nBefore the embryo can implant in the endometrium, the endometrium must be in a receptive state. As a result of a series of timed hormonal events, the so-called window of implantation is opened, which is the time most suitable for the endometrium to support trophoblast-endometrial interaction [31].
\nThe term windows of vulnerability (WOV), i.e., period of time when the endometrium is subject to the influence of factors that may disrupt implantation conditions, has recently been introduced within the framework of reproductive medicine, besides the window of implantation (WOI), i.e., the optimal period of time of activation of endometrial receptivity (De Ziegler, personal communication, MSD symposium, Barcelona 2016).
\nPrepregnancy approaches such as weight management, blood pressure and blood sugar control, smoking cessation, and optimization of the pregnancy interval may improve implantation and placentation and lead to better pregnancy outcomes [32].
\nThere are a number of different treatment protocols for the “inadequate” endometrium. The medical treatment with estrogens, vasodilators, and sildenafil citrate has neither led to significant improvements of morphological parameters nor to the results in terms of increasing implantation and reduction of the number of miscarriages [33, 34]. There have been reports of trials with immunoglobulins and anticoagulants in pregnancy complication prevention [35, 36, 37, 38, 39]
The local endometrium therapy is ongoing for several years. One of the promising therapeutic targets is the corticotropin-releasing hormone (CRH). During implantation, corticotropin-releasing hormone plays a key role in facilitating endometrial decidualization and early maternal tolerance. The embryo implantation provokes the maternal endometrial response similar to the invading semi-allograft that produces acute inflammatory response. After the implantation, the embryo suppresses this response and prevents the rejection [40]. The deregulation of expression pattern of CRH was associated with unfavorable reproductive outcomes as well as chronic endometrium-derived inflammatory disorders, such as endometriosis and adenomyosis [41]. Positive outcome was found after the intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) [41] especially when pretreated with corticotropin-releasing hormone that acts by regulating apoptosis of activated T- lymphocytes at the implantation site [42]. The results of eight studies showed that intrauterine administration of activated autologous peripheral blood mononuclear cells prior to embryo transfer improves the reproductive outcomes in women with repeated implantation failure [43].
\nBesides endometrial receptivity, another very important parameter is the endometrial thickness. Defined minimal thickness at approximately 7 mm and clinical pregnancy rates after embryo transfer increase with increasing endometrial thickness. One of the new therapeutic approaches to improve endometrial thickness is the intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF). In clinical reproduction, G-CSF has been proposed as a treatment for implantation failure and repeated miscarriages, two indications for which a US patent has been issued. These authors have applied the drug subcutaneously [44]. Gleicher’s papers on flushing uterus cavity with growth factors before the embryo transfer have proposed granulocyte colony-stimulating factor as the treatment of implantation failure and repeated miscarriages [44]. Chang reported successful endometrial expansion in a small group of women with thin endometrium resistant to standard treatments, who were able to proceed to embryo transfer and conceive after uterine perfusion with G-CSF [45].
\nThe use of platelet-rich plasma (PRP) to improve endometrial receptivity is gaining increasing attention in assisted reproduction technologies. Platelets contain a significant amount of growth factors that have positive effects on local tissue repair and endometrial receptivity. Several authors have reported autologous PRP intrauterine injection improves pregnancy and birth rates, especially in patients presenting poor endometrial growth [46].
\nChang and associates have recently published the attempt to improve the quality of endometrial thickness, implantation rate, and pregnancy success and to reduce the complications and miscarriage rate, by flushing the uterus cavity with autologous platelet-rich plasma in preparation for the implantation during IVF process [47]. Farimani reported the first successful pregnancy after administration of PRP in a woman with recurrent implantation failure [48]. Kim et al. suggested that the use of autologous PRP improved not only endometrial thickness but restored the endometrial receptivity of damaged endometrium and increased the implantation, pregnancy, and live birth rates (LBR) of the 24 patients with refractory thin endometrium [49]. This therapy delivers biological growth factors, PDGF, TGF-b, and VEGF, insulin-like growth factor 1, epidermal growth factor (EGF), and epithelial cell growth factor to the endometrium. Our group has, so far, treated 25 patients with PRP technology and has achieved a significant improvement of the implantation rates and in reducing the number of abortions. We reported the first case of human embryo obtained after autologous platelet leukocyte-rich plasma (PLRP) in vitro activation of ovaries by interrupting Hippo signaling and PLRP stimulating AKT pathway with ultrasound-guided orthotropic re-transplantation [50]. The patient was a case of an early menopausal woman for whom the ovarian cortex was frozen, thawed, and treated with autologous PLRP which was then transplanted into her menopausal ovaries. Two months after the procedure, follicle formation was noted, and an egg was retrieved resulting in a single embryo [50].
\nThe human endometrium is a dynamic tissue that undergoes monthly cyclic changes, including proliferation, differentiation, and degeneration. Apoptosis is the common pathway of cell death for eliminating senescent endometrial cells from the functional layer of the human endometrium during the late secretory phases of the cycle. It has recently been implied that autophagy is involved in the endometrial cell cycle affecting apoptosis and is the most prominent during the late secretory phase [51]. It is known that the impact on autophagy processes in the endometrium may lead to a reduced incidence of pregnancy complications related to the implantation. Our group has proved that autophagy, a process of controlled self-digestion involved in cellular homeostasis, is dysregulated in endometrial tissue of polycystic ovary syndrome (PCOS) patients and that treatment with metformin might influence endometrial autophagy in PCOS [52]. Other studies reported that metformin can improve endometrial receptivity, enhance endometrial vascularity and blood flow, and revert endometrial hyperplasia and carcinoma into normal endometria in addition to improving hyperandrogenism and insulin resistance in some women with PCOS [53, 54].
\nThe essential requirements for normal implantation and subsequent placentation leading to a healthy gestation are receptive endometrium and healthy embryo. However, there is still a growing number of unexplained failed implantation outcomes that could not be assigned to known factors and require further investigation.
\nIn recent years it was indicated that different etiologies of infertility arose as a result of the underlying genetic and epigenetic changes that contribute to the endometrial dysfunction and lead to implantation failure, miscarriage, and adverse outcomes. These epigenetic and genetic changes lead to placentation defects and contribute to the short- and long-term outcomes associated with infertility. One of the main causes for altered genetic and epigenetic regulation of embryo development and placentation was assigned to hormonal and nutrition-related changes in maternal environment. Embryos respond to the in vivo maternal environment during gestation or during cultivation in vitro in multiple ways that can influence their future growth and health. Developmental plasticity could be altered by the changes in imprinted gene expression, nutrient, and stress-related signaling pathways or cell cycling and apoptotic rates. Embryo phenotype changes through a complex network of interactions with a central role for maternal-fetal neuroendocrine signaling [55]. Maternal undernutrition during gestation alters maternal steroid hormone levels, including elevation of glucocorticoids (GC; corticosterone, cortisol), the stress hormones, which can alter the physiological condition of the conceptus and affect the intrauterine fetal and postnatal growth and cardiovascular and metabolic physiology and enhance the risk of adult-onset disease. This exposure of the embryo to glucocorticoids can alter the fetal hypothalamus pituitary adrenal (HPA) axis, leading to increased fetal GC activity which can, in turn, modify the expression of many downstream-regulated genes that control growth and metabolism, including cardiovascular and renal physiology [55].
\nThe influence of placental function and placental/fetal exchange on fetal programming has been in focus of the recent research. Now it has become widely accepted that maternal nutrition can have the long-term consequences on the offspring without necessarily affecting the size at birth. Altered embryo phenotypes induced by prenatal nutrition are associated with epigenetic modifications. Many imprinted genes contribute to placental function and nutrient exchange [56]. Early epigenetic effects in embryos caused by environmental conditions can lead to physiological impairment to growth due to reduced nutrient supply. There is now evidence from human studies and animal experiments that show the overnutrition and undernutrition during the prenatal period which have lifelong health effects for the offspring and induce the development of noncommunicable diseases during postnatal life [57].
\nBesides nutrition, the hormonal milieu at conception is known to affect a number of imprinted genes that are expressed during the preimplantation period. Hormonal status will be especially affected during fertility treatment, mostly during IVF. Because superovulation could lead to altered expression of endometrial genes critical to tissue remodeling and placentation, hyperstimulated hormonal status has been implicated in an increased risk for pregnancy complications related to abnormal placentation [58]. Although global methylation pattern was found to be similar among the IVF and spontaneous conceptions early during placentation in the first trimester, differential methylation has been identified in multiple loci between IVF and non-IVF fertility treatments pregnancies but not when compared with spontaneous conceptions. This suggests that there are differences in the infertile population that might be linked to specific treatments, including the hormonal hyperstimulation, that could affect gene imprinting [59]. Several studies have found that the use of ARTs is linked with irregular DNA methylation in human gamete, embryo, placenta, and umbilical cord samples [60, 61]. There were also studies that showed association between specific procedures with methylation differences in placenta, suggesting that specific fertility treatments affect the placental epigenome and function [62].
\nThe embryo has, in addition to the endometrium, the crucial importance for the success and regularity of the implantation and then placentation. The morphological assessment of the embryos’ quality is insufficient for the cognition of its biological resources. The new invasive and noninvasive techniques of embryo quality assessment have been developed. Nowadays, the invasive technology means preimplantation genetic testing (PGT), the aneuploidy screening, or diagnosis of specific genetic disorders of the embryo before the transfer by using next-generation sequencing (NGS). These tests include biopsy trophectoderm cells with blastocyst vitrification [63, 64, 65]. With trophectoderm biopsy, both maternal and paternal abnormalities can be studied. Possible disadvantages are the presence of mosaicism and the fact that the trophectoderm might not be a representative of the inner cell mass.
\nNoninvasive time-lapse embryo monitoring allows continuous embryo observation without the need to remove the embryo from optimal culturing conditions. The information on the cleavage pattern, morphologic changes, and embryo development dynamics could help us identify embryos with a higher implantation potential. It has also been shown that imaging phenotypes reflect the molecular program of the embryo, where individual blastomeres develop autonomously toward embryo genomic activation [66].
\nThis type of monitoring allows for the collection of much more information on the timing of the cleavages and the dynamics of the morphologic changes, with analysis of the kinetics of the events up until the blastocyst stage [67].
\nVarious kinetic and morphologic markers have already been found that are associated with the minimal likelihood of implantation and others that are predictive of blastocyst development, implantation potential, genetic health, and pregnancy [68, 69].
\nAfter the formation of the embryo, its fate is already determined. The gamete quality has the crucial part in the creation of the high-quality embryos. The conditions, in which oogenesis and spermatogenesis take place, have a crucial impact on the quality of embryos that is formed from these gametes.
\nThe evaluation of the oocyte quality based on morphological evaluation is not sufficient for an insight into the biological potential. It can identify those cells that have nuclear immaturity, significant degeneration, or major abnormalities. Recently, the developed strategies including the genomic, transcriptomic, and proteomic approaches have been applied in assisted reproduction. Their goal is to identify a “molecular profile” of embryo development by detecting the chemical components in the oocyte, granulosa cells, follicular fluid, and embryo culture medium [70].
\nBetter predictors, the birefringence properties of the meiotic spindle, and the zona pellucida are indicative of good health of the oocyte [71]. A very useful data can be obtained from the application of studying gene expression from cumulus cells, using microarrays, as biomarkers for oocyte viability
Magnetic-activated cell sorting (MACS) technology for sperm could improve obstetric and perinatal outcomes compared with those achieved after swim up. Treatment of sperm with MACS procedure prior to IVF results in a marked improvement in pregnancy rate and cessation of the abortion rate in couples whose ejaculates initially had high levels of SDF [76].
\nA number of prerequisites are needed to create high-quality oocytes, those conditions are likely to be grouped into several parts: the existence of high quality responsive oogonia, its potential of the adequate number increase and quality of mitochondria, the presence of sufficient amounts and types of growth factors, orchestrated by the balance of blocking (Hippo) and activating (ACT) gene pathways [77].
\nFor decades it was believed that the woman’s reproductive potential is entirely dependent on the size of the stock (pool) of primordial follicles in the ovary. The paradigm that has prevailed for decades in the scientific world about the existence of a consistent number of primordial follicles, established during embryonic and fetal period, was in many ways changed by Tilly’s group work. They practically demonstrated the existence of germline or oogonial stem cells [78].
\nTheir dormant status is characterized by communication with surrounding granulosa cells and numerous mechanical and chemical factors controlling the progression of their cell cycle. These factors control signaling activation of the pathways included in the primordial follicle dormant status regulation, like Hippo and AKT signaling [77]. During the recent years, various programs have been developed to try to improve the quality of oocytes. It has been shown that it can be influenced on the activation of primordial cells and maturation to the mature oocyte. The stem cells can be influenced by the stem cell therapy in order to obtain the intracellular communication with the existing ovarian primordial oogonia. The therapy with mesenchymal stem cells has led to the recovery features of oocytes after the chemotherapy-induced insufficiency [79]. The animal experiments by the in vitro therapy with developed stem cells have led to the birth of live offspring without abnormalities [80]. Other groups of authors have tried to improve the ovarian function with the growth factors obtained from the plasma and enriched with platelets and leukocytes. The cases of childbirth after re-transplantation of ovaries with support of PRP have been published [81]
The role of the number and function of mitochondria in the development of quality oocytes is surely very important. The problems of mitochondrial heteroplasmy go with the complicated, technologically very complex methods of polar body transfer, spindle transfer, and pronuclear or oocyte transfer [82, 83, 84]. The augmentation of autologous mitochondria carries a potential treatment. Our team has inaugurated the attempt of the mitochondrial energy boosting with ovarian high-intensity interval training (HIIT).
\nThe autologous growth factors that are intraovarian instilled are leading to the changes in the production and efficiency of the local growth factors. The influence on the genetic control of oogenesis, by the modification of the Hippo and AKT signaling pathways, is possible in different ways. The correction of the gene signaling or autologous tissue genetic bioengineering is certainly a step forward in obtaining the quality gametes [50, 84]
Implantation is one of the crucial periods in human reproduction. Increasing body of evidence suggests that the improper (dysfunctional) implantation and the formation of the placenta can endanger life and health of both the fetus and the mother, during prenatal life and decades after delivery. The changes that lead to the insufficient implantation should be sought in the preimplantation period, in relation between the embryo and the endometrium. It is possible that the time is approaching when the disorders of the pregnancy caused by dysfunctional implantation would be the indication for the application of a natural IVF (without ovarian stimulation) with the use of new biotechnological achievements. For better results of the perinatal medicine, it is necessary to apply earlier (in the preconception and preimplantation periods) the therapy based on the subcellular and genetic level by applying the latest biotechnological procedures.
\nThe growing interest in a healthy lifestyle has led the food industry to establish an alliance with the scientific community to create a viable and effective alternative for the consumer, carrying out several studies about the bioactive potential of various compounds present in natural matrices [1].
The recently discovered properties of phenolic compounds have been exploited, and the food industry has launched numerous new functional products whose health functionality is closely connected with their polyphenols content [2].
The scientific community have been developing several studies to determine the presence of phenolic compounds natural matrices, namely the presence of flavonoids. For example, in cereals, several kinds of flavonoids (principally glycosylated flavones) are distributed in these grass crops; in legumes, the presence of a total of 690 isoflavonoids have been reported; and in medicinal plants these molecules are a major constituent in lists of metabolites responsible for the bioactivities [3].
Flavonoids are a subdivision of polyphenols that are abundant in the human diet and can be found in several matrices; specifically, they are commonly found in fruits, vegetables, nuts, teas, dark chocolate, red wine and legumes [3].
These compounds are divided into principal subclasses of flavanols, including flavanol monomers (flavan-3-ols) and flavanol polymers (called proanthocyanidins), flavonols, flavanones, flavones, isoflavones, and anthocyanins (depending on the substitution at the heterocyclic ring (C-ring)) [4]. Regarding their physiological potential, flavonoids have a vast range of bioactivities, namely antioxidant, anti-inflammatory, vasorelaxant, anticoagulant, cardio-protective, anti-obesity and anti-diabetic, chemoprotective, neuroprotective, and antidepressant properties that are progressively being clarified [5]. These beneficial properties are strongly dependent on the polyphenols chemical structure [2].
Flavonols are the most important subgroup of flavonoids. Chemically, these compounds (as other flavonoids) have a characteristic 15-carbon skeleton (C6-C3-C6), two benzene rings constitute its structure (catechol B ring and resorcinol A ring) joined together by a 4-pyrone heterocyclic ring C (Figure 1) [6].
Chemical structure of flavonols. Designed with eMolecules (
Some compounds of this subclass include quercetin, myricetin, kaempferol, galangin, and fisetin [7, 8, 9]. These molecules represent the most ubiquitous and abundant flavonoids in the plant kingdom (dicotyledonous plants, especially flowers and leaves of woody) [10, 11] and occur abundantly in fruits (
The scientific community has widely studied the positive effects of flavonols on human health. These molecules have been reported as important antioxidants due to their abilities to suppress free radical formation, scavenge free radicals, and upregulate or protect antioxidant systems. They also inhibit the enzymes associated with free radical production, reduce lipid peroxidation, and chelate metal ions in reducing free radical generation [10, 11]. In addition to the antioxidant potential, these molecules have shown other target biological activities such as antimicrobial, anti-viral (interruption of virus’s entry and replication cycle) hepatoprotective, nephroprotective (effective for the treatment of chronic kidney disease), anti-inflammatory, vasodilatation effects, and cardiovascular protective effects (preventative role in coronary diseases). They also have been considered as potential anticancer agents [8, 13, 14].
However, despite all the flavonols have a broad spectrum of biological activities, kaempferol, myricetin, and quercetin are the main representatives and have been widely studied due to their health-promoting functions. Both kaempferol and quercetin have unique biological properties as anticarcinogenic, antimicrobial, antidiabetic, anti-viral, anti-allergic, antioxidant, and anti-inflammatory [7, 8, 11].
Flavanols or flavan-3-ols are another flavonoid subclass with a hydroxyl group at position 3 and a fully saturated carbon ring structure (Figure 2) [9].
Chemical structure of flavanol. Designed with eMolecules (
The most common flavan-3-ol monomers are catechin, epicatechin, catechin gallate, epicatechin gallate, gallocatechin, epigallocatechin, gallocatechin gallate and epigallocatechin gallate [2]. These compounds are widely spread in nature and can be found in a wide range of natural matrices as apples, peaches, cocoa powder, nuts, dark chocolate, grapes, berries and beverages (such as red wine, tea, and cider) [9]. Furthermore, they can also be found in certain food plants, such as
Over time, the interest in flavanols has grown, and different studies have reported these compounds’ health benefits. These compounds present several beneficial effects in consumers’ health, acting as antioxidant (scavenging of free radicals, chelation of transition metals, as well as the mediation and inhibition of enzymes), anticarcinogen, cardio-preventive (modulation of vascular homeostasis), anti-microbial, anti-viral, and neuro-protective agents [4, 18]. Besides, dietary intervention studies demonstrated that consuming certain flavanol-containing foods results in improved arterial function, a decrease in blood pressure, positive modulation of hemostasis, and improved insulin sensitivity [15]. In this sense, diets enriched in flavan-3-ol containing foodstuffs may provide beneficial health effects [17].
Flavones are also a subgroup of the flavonoid class based on the backbone of 2-phenylchromen-4-one (2-phenyl-benzopyran-4-one). The molecular formula of the flavone molecule is C15H10O2. It has a three-ring skeleton, C6-C3-C6, and the rings are referred to as A-, C-, and B-rings, respectively (Figure 3). These compounds are also characterized by the presence of three functional groups, including hydroxy, carbonyl, and a conjugated double bond. Consequently, they exhibit characteristic reactions of all three functional groups [19].
Chemical structure of flavones. Designed with eMolecules (
The most abundant types of flavones are luteolin, apigenin and chrysin [20]. These compounds are commonly found in edible vegetables, fruits, nuts, seeds and plant-derived beverages and cereals, which are ingested inadvertently in our daily diet and positively impact consumers’ health without significant side effects [3, 20].
The scientific community has carried out several studies to determine the biological potential of flavones. These molecules have received broad interest for their antioxidant potential [21] and their ability to modulate several enzyme systems involved in many diseases [22]. Also, these compounds have demonstrated to have other biological properties beneficial to health, namely anti-inflammatory activities [23], antibacterial [24], antifungal [25], antiviral [26] and anti-carcinogenic [27]. Furthermore, they also have immunomodulatory effects [28], and they intervene in the reduction of total cholesterol [29]. Recent studies in numerous disease areas (osteoporosis, prostate hyperplasia, endocrinology, and others) have shown that many disorders, specifically in the metabolic area, are multi-factorial and are better treated with combinations of drugs and natural products [19]. However, all these therapeutic actions depend and differ according to the different compounds belonging to the subclass of flavones [30].
Flavones are another subgroup of flavonoids and have a C6-C3-C6 skeleton composed of 3 rings, A-, C-, and B-, respectively, and a chiral carbon at the C-3 position (Figure 4) [31].
Chemical structure of flavanones. Designed with eMolecules (
Formerly, flavanones were considered minor flavonoids, like chalcones, dihydrochalcones, dihydroflavonols and aurones; nevertheless, in the past 15 years, the total number of known flavanones has increased, and they are now considered a major flavonoid class like flavones, isoflavones, flavanols, flavonols and anthocyanidins. Nowadays, in nature, up to 350 flavanone aglycones and 100 flavanone glycosides have been identified [32].
Flavanones are mainly divided into naringenin, hesperetin and eriodicthiol [20]. They are characteristic compounds of citrus fruit, principally lemon, lime, mandarin (tangerine), sweet orange, grapefruit, sour (bitter) orange and tomato [33, 34, 35]. These compounds are also widely distributed in around 42 plant families (
As in the other subgroups of flavonoids, flavanones also exhibit biological properties, which positively affect consumers’ health. Properties associated with flavanone intake include antioxidant [34], anti-inflammatory [36], antitumor, antiviral [37] and antimicrobial activities [38]. Furthermore, flavanones are related to some beneficial effects, such as improved gastrointestinal function [39], decreased blood cholesterol level [38], cardioprotective effect [40] and reduction of inflammatory responses caused by SARS-CoV-2 infection [35].
Some structural variation from flavones are presented in isoflavones, which differs from flavones in the location of the phenyl group’s location at C3 rather than C2 position (Figure 5) [9].
Chemical structure of isoflavones. Designed with eMolecules (
Isoflavones are divided into genistein, daidzein and glycitein [20]. These compounds are naturally-occurring plant compounds and are usually found in legumes from the
Isoflavones have also demonstrated bioactive properties that intervene beneficially in human health. The therapeutic effects of isoflavones are anti-inflammatory, antioxidant [43], anti-obesity [44] and antitumor activities [45]. Besides, several benefits are associated with isoflavones, such as relieving menopausal symptoms [46], hepatoprotective [47], cardiovascular protection [48], therapeutic potential in the control of diabetes [49], osteoporosis prevention and treatment [50], modulatory effect of the intestinal microbiota [51] and studies in rats have reported an improvement in kidney function in obese rats [52].
Anthocyanins belong to the large group of flavonoids, being considered the most revealing water-soluble pigments for extraction from natural matrices [53]. Regarding their chemical characterization, anthocyanins come from a basic structure of 3 rings of the C6-C3-C6 shape, defined as an aglycone portion, called the flavylic cation (Figure 6). When associated with chemical groups in the R positions, it is called anthocyanidin [53, 54].
Chemical structure of anthocyanins. Designed with eMolecules (
The most common types of anthocyanins are cyanidin, delphinidin, pelargonidin, peonidin, malvidin and petunidin [55]. The anthocyanin compounds are present in a composition of a wide range of vegetables (red onion, radish, red cabbage, red lettuce, eggplant, red-skinned potato and purple sweet potato), flowers (red hibiscus, red rose, red pineapple sage, red clover, and pink blossom) and several red fruits, such as: cherries, plums, strawberries, raspberries, blackberries, grapes, and many others [56, 57].
Anthocyanins are involved in many biological activities that positively impact human health. The use of these molecules for medicinal purposes has been long supported by epidemiological evidence. Still, just in recent years, some of the specific, measurable pharmacological properties of isolated anthocyanin pigments have been proven by controlled
The bioactive properties of flavonoids are directly linked to the functions they exert. Flavonoids, present in higher plants’ cells, have a protective role against parasites and other pathogens (participating in allelopathy processes), herbivores, and ultraviolet (UV) radiation [61]. They have a regulatory function like most lipid-soluble vitamins and act as pollinating agents. The varied colors they can have attract pollinators, thus contributing to plant seeds’ dispersion [62]. The following sections display a set of functions attributed to these compounds, seeking to relate their bioactivity to their chemical features and/or possible mechanism of action.
The antioxidant properties of flavonoids have been recognized over the years. Given the wide presence of flavonoids in various fruits, vegetables, legumes, grains and nuts, these compounds represent approximately two-thirds of the phenols consumed in the diet, being the class predominantly described [63, 64]. The mechanisms underlying the antioxidant properties of flavonols include eliminating free radicals and the chelating activity of transition metal ions, being the preventive action and chain-breaking mechanisms responsible for the high bioactivity of flavonoids [65, 66]. In fact, flavonoids can eliminate free radicals and reduce their formation and/or their effects. As expected, the chemical structure plays a key role in the antioxidant activity of flavonoids. That is, due to the reducing capacity of the phenolic hydroxyl groups (presence of hydrogen-/electron-donating substituents), flavonoids can donate hydrogen; thanks to the ability to delocalize the unpaired electron leading to the formation of a stable phenoxyl radical, flavonoids can protect against damage caused by reacting oxygen species (ROS), and flavonoids can chelate transition metals capable of promoting the formation of hydroxyl radicals in reduced forms through the Fenton reaction under abnormal conditions. This property is strongly dependent on the arrangement of hydroxyls and carbonyl group around the molecule [66]. Considering these characteristics that underlie the antioxidant potential of flavonoids, studies carried out over the years have shown that the flavonoids with greater antioxidant activity have the following structure features: (i) a certain hydroxylation pattern, particularly in the ring B, namely 3′,4′-dihydroxyl group (
If the abovementioned features favor the antioxidant potential of flavonoids, on the other hand, the presence of saccharide groups seems to reduce the antioxidant properties of these molecules. Still, some studies showed that
However, the abundant consumption of flavonoids, as polyphenols in general, through the daily diet does not always correspond to obtaining the effects observed
The antimicrobial properties of natural products rich in flavonoids have been reported and recognized since antiquity. Of the best-known products, propolis can be highlighted, whose healing properties have been mentioned for thousands of years and used to treat wounds and ulcers. In fact, propolis’s antimicrobial properties have been attributed to its high content of flavonoids, particularly galangin and pinocembrin [72]. As previously mentioned, flavonoids’ bioactivity is related to their function in nature, namely protecting plants against pathogens. In this way, plant-derived flavonoids have different antibacterial mechanisms of action than conventional drugs, and generally, their bioactivity does not confer resistance. In fact, to the best of our knowledge, no report claims to have observed bacteria developing resistance to plant-based antimicrobials. In this way, antibacterial agents based on natural extracts rich in flavonoids represent an important alternative in developing new antibacterial formulations, both from a clinical perspective, as in any other application such as the food sector [73]. The possible mechanisms of antimicrobial action of flavonoids are briefly: (i) cell envelop synthesis inhibition (
Polyphenols’ prebiotic effects have also been explored, with available reports from pre-clinical and clinical studies. Flavonoids have been the most investigated phenolic compounds in terms of their effects on the composition of the intestinal microbiota and the health benefits of the host [75]. It must be highlighted that the current definition of prebiotic recognizes that, in addition to the stimulation of
In clinical trials, anthocyanins consumed in a wild blueberry drink have been studied, in a dose of 25 g/250 mL of water. The study included 20 healthy male individuals, with a 6-week consumption of the drink. After this period, an increase of
Color is the most important sensory perception that defines consumer expectations about foods’ organoleptic properties [80]. Thus, adding or improving food color has been one of the food industry’s commitments to make products more appealing. Although each coloring agent used by the food industry in the European Union is subjected to a rigorous safety assessment, some problems of intolerance and/or allergies or hyperactivity have been related to its consumption [81], which may justify the consumer’s preference for natural additives to the detriment of the artificial counterparts. In this way, the scientific community has been looking for natural alternatives to the artificial colors widely used in the industry. The major natural pigments obtained from nature include chlorophylls, carotenoids, betalains and flavonoids. Among the main classes of flavonoids used as coloring agents, the flavonols and anthocyanins stand out, obtaining a range of colors between cream, yellow, pink, red, blue and black [82]. There is already a natural coloring agent, based on flavonoids, approved by the regulatory authorities for its use in the food sector, namely anthocyanins (E163). The approved anthocyanin extract is obtained from the natural strains of vegetables and edible fruits, including blackcurrant pomace and grape skin [83]. The pH strongly influences the color of anthocyanins. In acidic conditions, anthocyanins are red, while in basic pH, they appear blue, being purple in solutions with neutral pH. Hence, grapes are one of the best sources of this natural red pigment, since their anthocyanins are largely methylated, leading to an increase in color intensity and higher stability [84, 85]. After consulting the literature, we found that most studies on natural food colors based on flavonoids are strongly focused on anthocyanins. Other classes of flavonoids have been studied as copigments. Given the sensitivity of anthocyanins to various factors, not only pH but also temperature, light, oxygen, among others. Copigments or other co-solutes can be added, even when colorless, since they trigger a hyperchromic effect [82]. Copigmentation may occur by forming (in the presence or absence of metal ions) noncovalent complexes involving an anthocyanin or anthocyanin-derived pigment (
Besides the properties previously described, some other bioactivities have been assigned to flavonoids, such as anti-diabetic, anti-inflammatory or anticancer activities. For instance, a new approach to treat diabetes with enhanced antidiabetic activity from a flavonoid nanoparticulate system has been proposed. This system with new biodegradable releasers would increase the solubility of flavonoids and consequently their bioavailability, preventing flavonoid from first-pass metabolism and intestinal absorption in the form of a flavonoid nanoparticulate system. Flavonoids exert their antidiabetic properties by enhancing insulin secretion via regeneration of pancreatic β-cells, enhancing insulin-mediated glucose uptake by target cells, inhibiting aldose reductase and increasing Ca2+ uptake [88]. Antidiabetic activity of flavonoids depends on the chemical criterion (C-2-C-3 double bond and ketonic group at C-4 position on ring B) which is fundamental for the bioactivity of polyphenols [89]. The antioxidant and anti-inflammatory activity of the flavonol fisetin (7, 3′, 4′-flavon-3-ol) has been evaluated, showing that it could improve the plasma insulin and antioxidant levels in diabetic rats and significantly decrease the levels of blood glucose. Therefore, the authors suggested that fisetin could be considered as an adjunct for the treatment of diabetes [90]. Regarding anthocyanins, in addition to their coloring capacity, other studies suggest that these flavonoids also have bioactivity with a potential impact on human health, namely antioxidant activity, chemopreventive potential, anti-inflammatory and immunomodulatory properties [91]. Some of the bioactivities attributed to flavonoids have been specifically pointed to flavonoid glycosides. For example, the
According to the current and continuously increasing demand for new healthy products for a better lifestyle of the population, an increase in the number of techniques used to extract bioactive compounds has occurred. Choose the best extraction technique for each sample is essential in terms of the quality and quantity of the target molecules obtained, that is, flavonoids. Nowadays, there is many extraction techniques that can be employed. These techniques are selected depending on the characteristics of the raw material, which are, in general, plants, food or liquid samples such as wine, tea or olive oil [94]. Independently of the source, the samples must be homogenized. Hence, the most used methods are grinding, milling, filtration, pulverizing and mechanical stirring. Depending on the raw material, before or after homogenization, a pretreatment could be used to facilitate or improve the homogenization and the extraction process. The pretreatments usually used are freezing (in a freezer or by liquid nitrogen), different drying process and freeze-drying [95]. However, the use of these pretreatments can affect the extract characteristics, limiting the optimization of the extraction process [96, 97, 98]. There is no standard for every source of raw material, so selected pretreatments must be chosen depending on the physical and chemical characteristics of the samples. Moreover, depending on the pretreatment and homogenization method, the sample must be stored in the appropriate conditions or perform the extraction immediately before the homogenization and the pretreatment [99, 100]. The extraction techniques can be divided into two groups, conventional and novel approaches.
Conventional extraction techniques are characterized using conventional solvents, with or without heat and usually under agitation. In a standard conventional extraction, the sample is homogenized and submerged in a solvent or a mix of solvents. Using this extraction methodology, flavonoids are obtained through the diffusion and mass-transfer phenomena [101, 102]. The most used methods are maceration and Soxhlet. Nevertheless, other techniques like percolation, hydro-distillation, boiling, reflux and soaking can be used [103, 104]. The advantages of using these techniques are their simplicity and low cost, so they are preferred by companies [102]. On the other hand, these methods have several disadvantages: high volumes of solvent, low extraction yields and long times. Furthermore, due to the sensitivity of flavonoids to high temperature, in extraction assisted by heat, the compounds’ biological properties could be affected [105, 106].
For its simplicity and low cost, extraction by Soxhlet is the most used [106]. The main advantages of this method are three. The first one is that through repeated cycles, the sample is in contact with fresh solvent almost all the time, helping the displacement of the mass transfer equilibrium. In the second place, after the extraction, it is not necessary to filter the sample. Lastly, the amount of sample extracted can be improved easily by simultaneous parallel extraction, which needs very little investment. However, Soxhlet extraction has some disadvantages concerning other conventional extractions. The main disadvantages of this technique are its duration (
Significant differences in the extraction yields between different conventional extractions can be observed. There are also differences between the number of compounds obtained and their bioactivity within the same method. These variations are caused by the parameters directly implicated in the extraction process like temperature, time, number of extractions (cycles), the ratio of solvent to raw material or type of solvent [108]. Table 1 shows diverse examples of extractions carried out under different conditions and different methods to compare the conventional extraction methods.
Type (cycles) | Substrate | Solvent (%) | Temperature (°C) | Time (min) | Yields | References |
---|---|---|---|---|---|---|
Batch | Ethanol | 50 | 50 | 2.04 mg/g dw | [109] | |
HRE | Eth:W (80:20) | — | 150 | 1.16% (Flavonoid extraction yield) | [110] | |
Mac | Eth:W (70:20) | 25 | 2880 | 5.6 mg/g dw | [111] | |
Reflux | Eth:W (70:20) | — | 150 | 6.8 mg/g dw | [111] | |
SAE | Eth:W (52:48) | 30 | 30 | 12.77 ± 0.65 mg/g dw | [112] | |
SBE | Ethanol | 50 | 450 | 48.15 mg RE/g | [109] | |
Soxhlet | Ethanol | 60 | 460 | 67.85 mg RE/g | [109] | |
Soxhlet | Eth:W (80:20) | — | 300 | 1.48% (Flavonoid extraction yield) | [110] | |
Soxhlet | Ethanol | 90 | 180 | 10.67 ± 0.27 mg/g dw | [112] | |
Soxhlet | Eth:W (70:30) | — | 300 | 7.0 mg/g dw | [111] | |
Soxhlet | Methanol | — | 300 | 0.40 ± 0.03 mg QE/g dw | [113] | |
Soxhlet | Ethyl acetate | 77 | 480 | 11.4 ± 0.6 (wt% extract) | [114] | |
Soxhlet | Metanhol | 65 | 480 | 25.8 ± 0.7 (wt% extract) | [114] | |
Soxhlet | N-hexane | 69 | 480 | 6.7 ± 0.2 (wt% extract) | [114] | |
Soxhlet | Ethanol | 78 | 480 | 25.8 ± 0.9 (wt% extract) | [114] | |
Soxhlet | Methanol | 40 | 360 | 267.33 ± 3.12 mg/g dw | [115] | |
Soxhlet | Ethanol | 360 | 218 ± 4.24 mg/ dw | [115] | ||
Soxhlet | Petroleum ether | 360 | 30.47 ± 2.34 mg/g dw | [115] | ||
Soxhlet | Eth:W (70:30) | 360 | 257 ± 3.47 mg/g dw | [115] | ||
Soxhlet | Methanol | — | 2880 | 11.5 mg/g dw | [116] | |
ASE | Met:W (80:20) | 80 | 10 | 3.9 mg/g dw | [117] | |
ASE (3) | Eth:W (40:60) | 40 | 30 | 49.22 mg GAE/g dw | [118] | |
ASE (3) | Eth:W (40:60) | 80 | 30 | 41.46 mg GAE/g dw | [118] | |
ASE (3) | Ethanol | 40 | 30 | 110.89 mg GAE/g dw | [118] | |
ASE (3) | Ethanol | 80 | 30 | 101.61 mg GAE/g dw | [118] | |
ASE (1) | Eth:W (70:30) | 40 | 10 | 72.60 mg GAE/g dw | [118] | |
ASE (1) | Eth:W (70:30) | 80 | 10 | 79.43 mg GAE/g dw | [118] | |
ASE (5) | Eth:W (70:30) | 40 | 50 | 65.78 mg GAE/g dw | [118] | |
ASE (5) | Eth:W (70:30) | 80 | 50 | 84.53 mg GAE/g dw | [118] | |
ASE (1) | Eth:W (40:60) | 60 | 10 | 58.54 mg GAE/g dw | [118] | |
ASE (1) | Ethanol | 60 | 10 | 85.83 mg GAE/g dw | [118] | |
ASE (5) | Eth:W (40:60) | 60 | 50 | 60.21 mg GAE/g dw | [118] | |
ASE (5) | Ethanol | 60 | 50 | 80.31 mg GAE/g dw | [118] | |
ASE (3) | Eth:W (70:30) | 60 | 30 | 60.57 mg GAE/g dw | [118] | |
ASE (3) | Eth:W (70:30) | 60 | 30 | 63.70 mg GAE/g dw | [118] | |
ASE (3) | Eth:W (70:30) | 60 | 30 | 60.89 mg GAE/g dw | [118] | |
ASE | N-hexane | 200 | 13 | 839.2 ± 232.3 QE/100 mg dw | [119] | |
ASE (2) | Water | 100 | 20 | 4.83 ± 1.52 mg/GAE g dw | [120] | |
ASE (2) | Methanol | 100 | 20 | 15.3 ± 0.6 mg/GAE g dw | [120] | |
ASE (2) | Met:W (50:50) | 100 | 20 | 4.28 ± 0.24 mg/GAE g dw | [120] | |
ASE (2) | Met:AA (99.5:0.5) | 100 | 20 | 11.58 ± 0.5 mg/GAE g dw | [120] | |
ASE (2) | Acetone | 100 | 20 | 13.8 ± 0.6 mg/GAE g dw | [120] | |
ASE (2) | A:W (50:50) | 100 | 20 | 13.2 ± 0.3 mg/GAE g dw | [120] | |
ASE (2) | A:AA (99.5:0.5) | 100 | 20 | 13.5 ± 0.8 mg/GAE g dw | [120] | |
ASE (2) | Met:W:AA (50:49.5:0.5) | 100 | 20 | 15.1 ± 0.1 mg/GAE g dw | [120] | |
ASE (2) | A:W:AA (50:49.5:0.5) | 100 | 20 | 14 ± 1 mg/GAE g dw | [120] | |
Mac | Ethanol | 60 | 120 | 70.13 ± 4.43 mg QE/g dw | [121] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.32 ± 0.05 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.18 ± 0.01 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.1 ± 0.01 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.1 ± 0.01 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.94 ± 0.7 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.44 ± 0.07 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.045 ± 0.002 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.51 ± 0.04 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.08 ± 0.01 mg GAE/g fw | [122] | |
Mac (2) | A:W (70:30) Methanol | 4 | 1440 | 0.32 ± 0.02 mg GAE/g fw | [122] |
Summary of studies of extraction of flavonoids from different sources.
SBE: sequential batch extraction; HRE: heat reflux extraction; SAE: stirring-assisted extraction; QE: quercetin equivalent; RE: rutin equivalent; Mac: maceration; AA: acetic acid; A: acetone; MA: maceration with agitation; GAE: gallic acid equivalent; ASE: accelerated solvent extraction; dw: dry weight; and fw: fresh weight.
Non-conventional extraction techniques put their effort in concentrate the energy to extract the bioactive compounds in a more efficient and/or selective way than in conventional extractions. Nowadays, methods that employ microwaves, ultrasounds, high pressure, supercritical fluids or digestive enzymes can extract more compounds of interest at a lower cost. Moreover, these novel techniques decrease the extraction time, increase the compounds’ selectivity and reduce the amount of solvent per extraction. In addition to solvent reduction, some of these techniques allow the use of solvents less harmful to the environment and human health. Therefore, some of these techniques are green methods that can be used with green solvents. This fact has prompted companies to optimize these techniques for subsequent implementation on an industrial scale [101, 123].
The parameter most characteristic of ultrasound is the frequency. The frequency of ultrasound is between 20 kHz and 10 MHz, while the frequency of sound is between 16 Hz and 20 kHz. The ultrasound-assisted extraction (UAE) uses one of the two types of ultrasound, power ultrasound (low frequency and high intensity), to extract different compounds from a wide variety of sources [124]. The mechanism of action of UAE consists in the formation of cavitation bubbles in the medium or solvent used. The appearance of voids by the compression and rarefaction cycle, which subjects the liquid to points above its critical molecular distance, creates cavitation bubbles in the medium. The compression and rarefaction cycle produce the enlargement of the bubbles until the bubbles collapse. This collapsing liberates a considerable amount of energy and subject the medium to high temperatures (4726.85°C) and pressures (2000 atm) now of the collapse. This extreme condition produces microjets that can break solid surfaces like vegetable cells favoring intracellular compounds’ extraction. Moreover, microjets also benefit the solvent-substrate interaction by reducing the particle size [124, 125, 126].
This method has been used in the food and pharmaceutical industries for several purposes [125]. The yield of the flavonoid extraction depends on diverse parameters: frequency, solvent, solid-solvent ratio. Table 2 shows numerous studies about the optimization of flavonoid extraction from different raw materials. Although UAE is considered a green extraction technique for their reduction of energy and time consuming, the use of green solvents with UAE is currently a new trend. In the case of flavonoids and other phenolic compounds, deep eutectic solvents (DES) are becoming a viable alternative to traditional polluting solvents (Table 2) [127, 128, 129, 130, 131]. The use of UAE has numerous benefits compared with other conventional and novel techniques. UAE obtains higher yields and productivity with lower extraction times and solvent consumption than the conventional techniques. Moreover, it is more ecofriendly and a wider variety of solvents can be used. Furthermore, the extraction can be carried out at low temperatures reducing the risk of thermal degradation of flavonoids. Nevertheless, UAE has some drawbacks. Before the extraction, a filtration step is required, and the unstable compounds are not suitable for this method [132].
Type (cycles) | Substrate | Solvent | Temperature (°C) | Time (min) | Yield | References |
---|---|---|---|---|---|---|
UAE | Eth:W (65:35) | 40 | 29 | 23.60 ± 0.31 mg QE/g dw | [72] | |
UADESE | CC:1,2-Propanediol (33:67) | Rt | 90 | 4.9 mg/g fw | [35] | |
UADESE | CC:Glycerol (33:67) | Rt | 90 | 2.9 mg/g fw | [35] | |
UADESE | CC:EG (33:67) | Rt | 90 | 8.7 mg/g fw | [35] | |
UADESE | CC:Malic a. (50:50) | Rt | 90 | 11.1 mg/g fw | [35] | |
UADESE | CC:Malonic a. (50:50) | Rt | 90 | 8 mg/g fw | [35] | |
UADESE | CC:p-Ta (33:67) | Rt | 90 | 88.9 mg/g fw | [35] | |
UADESE | CC:La. (33:67) | Rt | 90 | 16.5 mg/g fw | [35] | |
UADESE | CC: Oxalic a. (33:67) | Rt | 90 | 11 mg/g fw | [35] | |
UADESE | CC:Resorcinol (25:75) | Rt | 90 | 6.5 mg/g fw | [35] | |
UADESE | CC:Xylitol (50:50) | Rt | 90 | 3.2 mg/g fw | [35] | |
UADESE | CC: Urea (33:67) | Rt | 90 | 5.5 mg/g fw | [35] | |
UADESE | Water | Rt | 90 | 3.6 mg/g fw | [35] | |
UADESE | Methanol | Rt | 90 | 3.2 mg/g fw | [35] | |
UADESE | Ethanol | Rt | 90 | 4.2 mg/g fw | [35] | |
UAE | Water | 40 | 30 | 19.595 ± 2.114 mg GAE/g dw | [73] | |
UAE | Eth:W (72:28) | 65 | 37 | 16.45 ± 0.2 mg/g dw | [74] | |
UAE | Eth:W (60:40) | 64 | 47 | 16.4 mg/g dw | [75] | |
UAE | Eth:W (41:59) | 79 | 30.5 | 36.2 mg/g dw | [76] | |
HPAE | Eth:Water (50:50) | 25 | 3 | 5.8 ± 0.1 mg QE/g dw | [77] | |
UAE | Eth:Water (50:50) | 25 | 20 | 5.9 ± 0.2 mg QE g dw | [77] | |
HHPE | Hexane:W (60:40) | 20 | 10 | 21.5 ± 0.1 mg QE g dw | [78] | |
HPAE | Methanol | 150 | 240 | 15.5 mg/g dw | [79] | |
HPAE | Eth:W (75:25) | 80 | 120 | 200 ± 8.63 mg/g dw | [80] | |
MAE | Eth:W (80:20) | 50 | 1 | 77.26 mg RE/g dw | [16] | |
MAE | Eth:W (80:20) | 80 | 4 | 37.18 mg QE/g dw | [81] | |
MAE | Ethanol | Rt | 4 | 135 ± 3 mg QE/g dw | [82] | |
MAE | Eth:E (60:20) | 65 | 25 | 97.19 mg/g dw | [83] | |
MAE | Eth:W (90:10) | 110 | 25 | 1.19 ± 0.04 mg dw | [84] | |
SFE (CO2) | Eth:W (90:10) | 52.5 | 113 | 29.011 mg/g dw | [85] | |
SFE (CO2) | Eth:W (95:05) | 65 | 270 | 18.92 mg QE g dw | [86] | |
SFE (CO2) | Eth:W (20:80) | 51 | 120 | 4.24 mg/d dw | [87] | |
SFE (CO2) | Ethanol | 50 | 90 | 16.95 ± 0.43 mg/g dw | [88] | |
SFE (CO2) | Eth:W (10:80) | Rt | 30 | 72.18 ± 1.13 mg/g dw | [89] | |
SFE (CO2) | Eth:W (96:4) | 50 | 70 | 58 mg RuE/g dw | [90] |
Parameters that affect novel extraction techniques of flavonoids from different sources.
UAE: ultrasound-assisted extraction; CC: choline chloride; EG: Ethylene glicol; a.: acid; p-Ta: p-toluenesulfonic acid; La.: levulinic acid; UADESE: ultrasound-assist deep eutectic solvent extraction; HPAE: high pressure assisted extraction; HHPE: high hydrostatic, pressure extraction; Rt: room temperature; SFC-CO2: supercritical CO2 fluid extraction; dw: dry weight; and fw: fresh weight.
Le Chatelier’s principle states that if a system in equilibrium is perturbed, it restores the balance changing other parameters [133]. Therefore, if a system (solvent – raw material) is subjected to an increase in pressure, it will suffer a decrease in volume that will result in a more efficient extraction [134]. The volume changes produce variations in the cellular membrane and other big molecules that can cause the cell membrane and organelles’ rupture, thus facilitating the transfer of bioactive compounds to the solvent [135]. The process of high pressure-assisted extraction (HPAE) has three stages. Firstly, the sample is mixed with the solvent in the pressure vessel at ambient pressure. The sample is subjected to a sudden pressure change up to 100–1000 MPa. At this point, the plant cell wall, the cell membrane, or any other barriers are subjected to a large differential pressure between the inside and outside of the barrier producing deformations and ruptures. The solvent penetrates the barriers through the ruptures and deformations, accessing the cell interior. Once the solvent is in the cell interior, the mass transfer of soluble compounds is favored. Moreover, the differential pressure could exceed the cell’s deformation limit (cell wall and/or membrane). This will collapse, resulting in the liberation of all the compounds which will flow to the outside and dissolved in the solvent. Finally, all pressure is quickly released to atmospheric pressure, which produces cell expansion deforming the cell wall and membrane again [136]. The parameters that are usually considered at the time of the extraction are: temperature, pressure, type of solvent and concentration, holding pressure time, the ratio of solvent to raw material and the number of cycles [137]. Table 2 shows how some of these parameters affect the extraction of flavonoids.
Regarding their advantages, the use of HPAE has demonstrated that the extraction could be performed at low temperatures without damaging heat-sensitive compounds or other compounds. Moreover, HPAE is considered an environment-friendly process, so it is a suitable alternative [138]. Other advantages are: the possible combination of more than one solvent to extract more than one type of compound, short periods of extraction, low use of energy or high cell penetration, resulting in higher mass transfer and extraction performance [137]. Nevertheless, in most cases, this technique uses some contaminant solvents, and after the extraction process, a filtration step is mandatory [139].
The microwave-assisted extraction (MAE) consists of applying electromagnetic waves to produce changes in the cell wall and membrane. Microwaves have a frequency between 300 MHz and 300 GHz and belong to the electromagnetic field [140]. The MAE process’s main advantage is the synergetic combination of heat and mass gradients flowing in the same direction [141]. The electromagnetic waves interact with the polar components inside the cells producing heat through ionic conduction and dipole rotation only in the compounds with an adequate dielectric constant [142]. Depending on the interaction between the compounds and the microwaves the compounds can be classified into three categories: opaque, transparent and absorbing materials. Microwaves heat only absorbing materials by the absorption of the energy of the electromagnetic waves. The mass transfer of flavonoids is produced because of the capacity to heat the cell’s intracellular volume, causing an increase of the intracellular pressure producing the collapse of the cell wall and membrane. Then, the compounds can flow out of the cell and the gradient of heat flows [143].
The yield of the flavonoid extraction will depend on the raw material and selected parameters, such as temperature and time of the extraction, composition of the solvent, solvent-to-feed ratio, microwave power, the water content of the matrix and the number of cycles for optimal extraction of flavonoids [141]. Table 2 shows the yields of some flavonoid extractions by MAE and how some parameters affect flavonoid recovery. In comparison with conventional extractions, MAE has demonstrated better time of the extraction, yield, selectivity and quality of the flavonoid extracted. Moreover, the amount of solvent required is lower than in other techniques [144]. Nevertheless, the solvent and target compounds must fulfill some characteristics, compounds must be polar, and solvent must be not too viscous and absorb microwave energy. However, thermally labile compounds cannot be extracted with this method and after the extraction, extract filtration is required [132].
A supercritical fluid (SF) is a homogeneous liquid in which the liquid and gas state’s demarcation surface disappears. This homogeneous state is caused by exceeding the critical point of temperature and pressure [145]. The diffusivity and density of a SF are between what is expected in a gas and a liquid. As the same as gases, SFs experience a change of density when temperature or pressure are altered, which can produce variations in the density affecting the solvating power [146]. Therefore, these phenomena can improve the solubility of the compounds in the SFs. Supercritical fluid extraction (SFE) is a complex process widely studied along the literature [145, 146, 147, 148]. Nowadays, CO2 is the most SF used for SFE. CO2 has some very advantageous characteristics for SFE, low critical temperature (32°C) and pressure (704 MPa). Moreover, CO2 in low concentrations is non-explosive, non-toxic, non-inflammable and is easy to purchase at a low price with a high degree of purity. Besides, CO2 has more than double the diffusivity of other fluids with lower surface tension and viscosity. Nevertheless, CO2 is more suitable for nonpolar compounds than for polar compounds [149, 150].
The main limiting parameters are temperature, pressure and time of extraction [151]. Table 2 shows how these parameters affect the yield of flavonoid SFE. Moreover, other factors like flow rate, modifiers and fractionation can affect the yield of the extraction [146]. The main advantages of SFE are rapidity, low amount of solvent, high selectivity and yield. On the other hand, SFE is a complex process with many parameters to optimize. High investment is needed, and specific alterations such as adding modifiers when extracting polar compounds are necessary [132].
The enzyme assisted extraction (EAE) consists of the disruption of the plant cell wall and membrane by the enzymatic digestion of the polysaccharides that conform these two barriers. The plant cell wall comprises a complex structural mixture of polysaccharides, such as hemicellulose, cellulose and pectin, together with other molecules such as structural proteins and lignin [152]. Pectin is composed of a chine of α-D-galacturonate and L-rhamnose units linked by glycosidic bonds in α-1,4 or 1,2 that create the structure called pectic elbows [153]. For the hydrolysis of pectin, several types of pectinases (protopectinases, esterases, depolymerases) are used in the juice industry but also in the extraction of polyphenols [154, 155]. Cellulose is a polymer consisting of glucose β-1,4, which linked to other molecules, gives protection and stability to the cell wall [156]. Cellulases catalyze the breakdown of cellulose. Although its mechanism of action is not fully established, the most accepted theory affirms that three different types of proteins work synergistically during cellulose catalysis. Endonucleases act first, followed by the cellobiohydrolases and, finally, exoglucanases, resulting in free glucose molecules [157]. Hemicellulose is a heterogeneous mixture of carbohydrates homologous to cellulose, such as xyloglucans and mannans. Hemicellulases are a big group of enzymes with several enzymatic activities to break down all hemicellulose forms [158]. Lignins refer to aromatic polymers resulting from the oxidative combinatorial coupling of 4-hydroxyphenylpropanoids [159]. Nowadays, enzymes kits for digestion of the cell wall are prepared to carry out the functions previously mentioned and thus liberate flavonoids in the cell interior and improve the solvent’s mass transfer [160]. Besides, EAE could be used alone or combined with other techniques (MAE, UAE, SFE or HPAE) [161].
Parameters like temperature and pH are essential when working with enzymes. Moreover, selected enzymes, mode of action and time are other parameters to consider [161]. Table 3 shows several studies of the extraction of flavonoids from different sources and the yield variation depending on some parameters that affect extraction efficiency. In terms of environmental pollution, this method is one of the most environmentally friendly. Besides, EAE could be performed at low temperature, valid for many different raw materials, and different enzymes can be selected depending on the targets of the extraction [160, 162, 163, 164, 165].
Substrate | Enzymes | Solvent | Temperature (°C) | Time (min) | Compound | Yield | References |
---|---|---|---|---|---|---|---|
Cellulase and pectinase | Eth:W (50:50) | 60 | 1800 | Flavonoids | 28.3 mg/g dw | [91] | |
Grape skins | Lallzyme EX-V (commercial) cellulase and hemicellulose, polygalacturonase, pectin lyase, pectin methylesterase | Water | 45 | 179 | Flavonoid glycoside and flavan-3-oil | 4 mg/g dw | [92] |
Grape skins | Lallzyme HC (commercial) cellulase, polygalacturonase, pectin lyase, pectin methylesterase | Water | 31 | 162 | Flavonoid glycoside and flavan-3-oil | 3.7 mg/g dw | [92] |
Grape skins | Endozym Rouge (commercial) cellulase and hemicellulose, polygalacturonase, pectin lyase, pectin methylesterase | Water | 39 | 85 | Flavonoid glycoside and flavan-3-oil | 3.7 mg/g dw | [92] |
Grape skins | Endozym Contact Pelliculaire (commercial) cellulase and hemicellulose, polygalacturonase, pectin lyase, pectin methylesterase | Water | 36 | 128 | Flavonoid glycoside and flavan-3-oil | 3.7 mg/g dw | [92] |
Cellulase, beta-glucosidase, pectinase | Water | 32.5 | 1080 | Luteolin and apigenin | 0.4 mg/g dw | [93] | |
Cellulase, pectinase | Water | 32 | 1080 | Flavonoids | 4.96 ± 0.29 mg/g dw | [94] | |
Cellulose ® MX, Kleerase ® AFP | Water | 50 | 180 | Phenolics | 1.62 mg GAE/g fw | [95] |
Parameters that affect enzyme assisted extraction (EAE) of flavonoids.
SBE: sequential batch extraction; HRE: heat reflux extraction; SAE: stirring-assisted extraction; QE: quercetin equivalent; RE: rutin equivalent; dw: dry weight; and fw: fresh weight.
Bioavailability refers to the concentration of a molecule or related like-molecules that become absorbed and available for exerting their biological activity in the site of drug action of the target tissue, organ or system [166]. The term bioavailability is strongly related to the concept of bioaccessibility and to bioactivity. Bioaccessibility refers to the number of compounds that, after digestion, becomes available and absorbable through the intestinal epithelium. This definition is linked to bioactivity, which involves the physiological effects that biomolecules trigger in the organism and includes their transport through systemic circulation to the target receptor and their interaction with other biomolecules [167].
The bioavailability of polyphenolic compounds has been described to be poor since they hardly reach bioaccessibility rates higher than 30–50% [167]. Among the parameters involved in this low bioavailability, there are several physicochemical properties of flavonoids which include their chemical structure, polymerization degree, solubility, variability of attached saccharides or potential interactions they established with other compounds, or flavonoids stability, both during storage and along the digestion process [168]. Different approaches have been developed to enhance the accessibility to the final number of flavonoids or to blur their metabolism through digestion and improve and extend their chemical stability. These intend to maximize the bioavailability of flavonoids. To increase the available concentration of flavonoids in food, different treatments have been applied to food matrixes. The main purpose is to alter the matrix’s structural organization in which biomolecules are embedded so they can get easily released. Both heating and freezing approaches have been tested and demonstrated to positively affect the bioaccessibility of polyphenols [167]. Nevertheless, other techniques requiring more technological development have demonstrated a better performance to improve flavonoids bioaccessibility (Figure 7). In fact, the pharmaceutical industry has established alternative approaches to improve the oral bioavailability of flavonoids with clinical applications. Some of the most utilized strategies are the use of absorption enhancers (nonionic surfactants, myo-inositol hexaphosphate, chitosan or pectin), the induction of structural transformations which include the introduction of functional groups with higher polarity (sulfuric acids, amino acids, carbamoyls, glycosides, etc.), or the complexation with a carrier (such as cyclodextrins, phospholipids or polymeric carriers) [169].
Strategies to enhance flavonoids bioavailability. Nanosuspension, nanoencapsulation or nanoemulsions have been proved as successful approaches to improve flavonoids solubility and enhance their bioavailability, bioaccesibility and, bioactivity.
Among these approaches, nanosuspension, in which pure drug particles are combined with stabilizers, has been demonstrated as a promising strategy to enhance the bioavailability of flavonoids. This system facilitates the delivery of flavonoids using particles in the nanometers range, which allows reaching a higher concentration quickly by increasing solubility and dissolution rates. For instance, in a recently published work in which different nanosuspension formulae were applied, the solubility of myricetin was increased from 43 to nearly 75 times. This increment was accompanied by an improved bioavailability in the relative range of 161–357% [169]. Another flavonol, quercetin, was also submitted to nanosuspension. This strategy improved its saturation solubility about eleven times which also provided a much better bioaccessibility. The bioaccesibility increased slowly, reaching its maximum peak between 2 and 3 h, while the pure molecule reached this maximum at 1.5–2 h. The amount of quercetin released from the nanosuspension was higher than the pure, duplicating its bioaccessibility even at the last measured times [170]. The bioactivity of the orally administrated flavanone, naringenin, was also tested using rats. It was shown that the nanosuspension of naringenin was nearly 4 times higher when compared against the control [171].
A common methodology applied in both food and pharmacological industries for increasing flavonoids bioavailability and bioaccesibility, which ultimately enhances their potential bioactivity, relies on their encapsulation [169, 172]. Different techniques, with diverse complexity degrees, permit the encapsulation of a considerable variability of core ingredients using different shell materials for obtaining capsules with various physical properties. Some of the most used encapsulation methods include spray or freeze-drying, spray chilling and cooling, coacervation, fluidized bed coating, liposome entrapment, rotational suspension separation, extrusion and inclusion complexation, (micro)emulsions, etc. [173]. The main aim of the encapsulation process is to prevent biological and physicochemical degradation of bioactive ingredients. Encapsulation permits to extend the chemical stability of the target molecules and thus their bioactivities. Besides, encapsulation may also allow the controlled release of the compounds delivered using concentrations. Scientific literature provides several examples of flavonoids that have been encapsulated. Among the benefits of encapsulation, bioaccesibility and bioavailability are two parameters that can be improved using this approach. Besides, encapsulation permits to embed flavonoids in the most appropriate matrices to reinforce their stability [172]. The flavonoid subclass of anthocyanins has been extensively used to evaluate the performance of different encapsulation techniques and materials. For instance, anthocyanins from grape peels have been submitted to encapsulation by emulsification/internal gelation using both spray and freeze-drying techniques. The former provided smaller microcapsules (0.6 μm) with higher encapsulation efficiency and better microcapsule and anthocyanins stability, which extended their release in simulated gastrointestinal digestion and improved their bioaccessibility [174]. Two major anthocyanins were identified in extracts from
Another technique tested for enhancing the bioavailability of flavonoids is based on their emulsion. This emulsion can be created by utilizing emulsifying agents or mixtures of oil-(co)surfactants-water, which permit the self-emulsion with a simple process, agitation. In fact, different alternatives of this approach have been proved successful for different kinds of flavonoids. Anthocyanins from blueberry fruits were micro-emulsified and their bioavailability and bioactivity were evaluated against the control (without vehicle). Non-purified and purified anthocyanins, especially malvidin-3-
Therefore, very different techniques have been proved to improve the poor solubility of flavonoids and to enhance their bioavailability, bioaccesibility and, hence, their bioactivity. Among these techniques, the most successful ones are based on the application of nanosuspensions, encapsulations or emulsions of the flavonoids.
Currently, consumers are increasingly aware of their healthier food choices, associating them with their health and well-being. In this way, there is a global demand on the part of the food industry to develop innovative natural products and health promoters that contain bioactive components [186].
Different bioactive ingredients, namely flavonoids, have been studied to adapt organoleptic, sensory and conservation properties. They have also been explored as functional ingredients with bioactive properties, such as antioxidant, anti-inflammatory and immunomodulatory referred to earlier in this manuscript [187, 188, 189]. Thus, bioactive compounds are considered valuable options to be explored in the design of innovative food formulations with health benefits.
Different flavonoids have been studied, and their bioactive properties have been proven by several authors, which has arisen the high interest of the food industry in their application in functional foods. Foods and beverages such as dairy products, bakery and confectionery products, meat products, juices and energy drinks, snacks, pasta, gums and sweets are some of the products explored the most in the addition of bioactive compounds [190].
In a recent study, the stability of anthocyanins from grape residues was evaluated when applied as a food coloring in carbonated water and proved that the degradation of the incorporated anthocyanins followed the kinetic behavior during storage, when exposed to light or dark [191]. The anthocyanin malvidin-3-glycoside showed the greatest stability when added to the water. Additionally, it was found that the light had adverse effects on the color of the carbonated water. Bakery and pastry products, recognized for providing consumers of all ages with pleasure and fun, have been explored exponentially in an attempt to find functional natural ingredients and/or colors with potential for application in a highly competitive area [192]. A recent study intended to explore the bioaccesibility and bioavailability of phenolic compounds (namely flavonoids) obtained from green tea in wheat bread. The results showed an increase in the nutraceutical potential and the protection of lipids against oxidation. Also,
Dairy products have been extensively tested and explored due to the industry’s high interest to supplement functional ingredients [195]. Aqueous extracts of
Some fruits have also been explored as natural ingredients. In a recent study, extracts from
However, incorporating these compounds in this type of food product has represented a challenge about the quality of the final product and the stability of bioactive compounds. The high-water content and low pH value of yogurt as well as the low solubility of polyphenols have represented a great challenge for the use of herbal extracts, especially hydrophobic extracts [200]. The use of bioactive compounds as natural ingredients in food products has been characterized in several studies as limited due to their stability and bioavailability. Storage conditions, thermal and non-thermal processes and extraction treatments are some of the parameters identified as responsible for affecting these compounds’ effectiveness [201, 202]. Some bioactive compounds are susceptible to environmental factors, namely pH, temperature, oxygen, enzymes, light, metal ions, sulfur dioxide and ascorbic acid [203]. The molecular interactions between bioactive compounds with other food ingredients can also affect some properties of these compounds, such as bioavailability, bioactivity and organoleptic properties [204]. After oral consumption, the chemical structure and bioactivities of the components are altered in intestinal metabolism. Thus, it is necessary to ensure that the bioactive compounds in the gastrointestinal tract are stable and allow controlled release at target points [205].
This type of limitations has been a concern for the food industry since it can hamper its industrial application. For example, quercetin is a flavonol recognized for its anti-diabetic properties; however, its low solubility and aqueous permeability limit its application. Anthocyanins, which are very attractive due to their ability to provide color and potential health benefits, have also represented a major industrial challenge in controlling their deterioration and increasing their bioavailability in food systems [206, 207].
For this reason, different microencapsulation and delivery systems have been explored to guarantee the production of functional foods with acceptable organoleptic characteristics and the controlled release of flavonoids, thus preventing interactions with other food components, and overcoming problems encountered during food processing and gastrointestinal transit [208, 209]. Some examples will be mentioned as follows. A blueberry-derived mixture of anthocyanins was encapsulated into chitosan nanoparticles, and its stability in a drink was evaluated. The results suggested that the chitosan nanoparticles delayed the anthocyanin degradation in the simulated gastrointestinal fluid and increased the anthocyanin storage stability in the drink [201]. In other work, an encapsulated polyphenolic extract (rich in anthocyanins) from Artemide black rice obtained through the atomization process with maltodextrins and gum arabic (50:50, w/w) was incorporated into biscuits. The results showed that the encapsulated ingredient emerged as the most stable during storage and cooking and with the most significant antioxidant capacity than the control biscuit [210].
Also,
The exploitation of natural ingredients with antioxidant and antimicrobial properties in combination with natural polymers has also been ceased by the scientific community in the development of edible films that allow to reduce the dependence on synthetic polymers and offer viable solutions for industrial application [214]. Polyamide, polyethylene terephthalate, ethylene vinyl alcohol, polyvinylidene chloride, polypropylene and polyethylene are some of the most widely used polymer materials in the food industry for food preservation. However, some authors report that polymers in direct contact with food allow the migration of the additives and other components to food, causing some adverse effects for consumers [215]. In this sense, studies on plastics and plasticizers and non-toxic bio-based food coatings to replace their synthetic counterparts have been increasing [216]. These coatings make it possible to coordinate natural polymers with bioactive ingredients from plant extracts with preservative and antimicrobial properties that improve the organoleptic and functional properties of food [217].
Although many bioactive compounds are currently tested in different food matrices to improve their organoleptic properties, to fortify and functionalize these same products, it is considered that the protection of such functional ingredients in the food matrix during processing, storage and passage the gastrointestinal tract has been little explored. Several flavonoids have been extensively studied and have shown to be highly promising bioactive compounds, capable of improving the physical-chemical, sensory and health properties of food products. However, studies on the effectiveness and interactions of these bioactive compounds for the development of new innovative products are still scarce and there are some gaps between digestion, metabolism and bioactive substance delivery approaches across biological barriers that must be explored. This type of studies’ transition to a commercial scale is an essential future step in innovation to provide more practical information that can be transposed to industry. Thus, and to meet consumers preferences and requirements, there is a great need for new and more complete
The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020); and L. Baros thanks the national funding by FCT, P.I., through the institutional scientific employment program-contract for her contract. The research leading to these results was supported by MICINN supporting the Ramón&Cajal grant for M.A. Prieto (RYC-2017-22891), by Xunta de Galicia and University of Vigo supporting the post-doctoral grant for M. Fraga-Corral (ED481B-2019/096), by EcoChestnut Project (Erasmus+ KA202) that supports the work of Bernabé Núñez-Estévez and M. Carpena; by IberoAmerican Program on Science and Technology (CYTED – AQUACIBUS, P317RT0003) and by the Bio Based Industries Joint Undertaking (JU) un-der grant agreement No 888003 UP4HEALTH Project (H2020-BBI-JTI-2019), the JU receives support from the European Union’s Horizon 2020 research and innovation pro-gram and the Bio Based Industries Consortium.
The authors declare no conflict of interest.
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Ahmed",authors:[{id:"175649",title:"Dr.",name:"Tarek A",middleName:null,surname:"Ahmed",slug:"tarek-a-ahmed",fullName:"Tarek A Ahmed"}]},{id:"29240",title:"Oral Absorption, Intestinal Metabolism and Human Oral Bioavailability",slug:"oral-absorption-intestinal-metabolism-and-human-oral-bioavailability-",totalDownloads:26955,totalCrossrefCites:24,totalDimensionsCites:55,abstract:null,book:{id:"672",slug:"topics-on-drug-metabolism",title:"Topics on Drug Metabolism",fullTitle:"Topics on Drug Metabolism"},signatures:"Ayman El-Kattan and Manthena Varma",authors:[{id:"85539",title:"Dr.",name:"Ayman",middleName:null,surname:"El-Kattan",slug:"ayman-el-kattan",fullName:"Ayman El-Kattan"},{id:"88221",title:"Dr.",name:"Manthena",middleName:null,surname:"Varma",slug:"manthena-varma",fullName:"Manthena Varma"}]},{id:"66742",title:"Introductory Chapter: Alkaloids - Their Importance in Nature and for Human Life",slug:"introductory-chapter-alkaloids-their-importance-in-nature-and-for-human-life",totalDownloads:3944,totalCrossrefCites:14,totalDimensionsCites:29,abstract:null,book:{id:"6828",slug:"alkaloids-their-importance-in-nature-and-human-life",title:"Alkaloids",fullTitle:"Alkaloids - Their Importance in Nature and Human Life"},signatures:"Joanna Kurek",authors:[{id:"214632",title:"Dr.",name:"Joanna",middleName:null,surname:"Kurek",slug:"joanna-kurek",fullName:"Joanna Kurek"}]},{id:"65128",title:"Natural Products in Drug Discovery",slug:"natural-products-in-drug-discovery",totalDownloads:6529,totalCrossrefCites:16,totalDimensionsCites:39,abstract:"Drug discovery using natural products is a challenging task for designing new leads. It describe the bioactive compounds derived from natural resources, its phytochemical analysis, characterization and pharmacological investigation. It focuses on the success of these resources in the process of finding and discovering new and effective drug compounds that can be useful for human resources. From many years, natural products have been acting as a source of therapeutic agents and have shown beneficial uses. Only natural product drug discovery plays an important role to develop the scientific evidence of these natural resources. Research in drug discovery needs to develop robust and viable lead molecules, which step forward from a screening hit to a drug candidate through structural elucidation and structure identification through GC–MS, NMR, IR, HPLC, and HPTLC. The development of new technologies has revolutionized the screening of natural products in discovering new drugs. Utilizing these technologies gives us an opportunity to perform research in screening new molecules using a software and database to establish natural products as a major source for drug discovery. It finally leads to lead structure discovery. Powerful new technologies are revolutionizing natural herbal drug discovery.",book:{id:"8290",slug:"pharmacognosy-medicinal-plants",title:"Pharmacognosy",fullTitle:"Pharmacognosy - Medicinal Plants"},signatures:"Akshada Amit Koparde, Rajendra Chandrashekar Doijad and Chandrakant Shripal Magdum",authors:[{id:"268668",title:"Dr.",name:"Akshada",middleName:"Amit",surname:"Koparde",slug:"akshada-koparde",fullName:"Akshada Koparde"}]},{id:"48805",title:"Biopharmaceutics and Pharmacokinetics",slug:"biopharmaceutics-and-pharmacokinetics",totalDownloads:26050,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"4491",slug:"basic-pharmacokinetic-concepts-and-some-clinical-applications",title:"Basic Pharmacokinetic Concepts and Some Clinical Applications",fullTitle:"Basic Pharmacokinetic Concepts and Some Clinical Applications"},signatures:"S. Lakshmana Prabu, T.N.K. Suriyaprakash, K. Ruckmani and R.\nThirumurugan",authors:[{id:"91590",title:"Dr.",name:"Sakthivel",middleName:null,surname:"Lakshmana Prabu",slug:"sakthivel-lakshmana-prabu",fullName:"Sakthivel Lakshmana Prabu"},{id:"128690",title:"Dr.",name:"Suriyaprakash",middleName:null,surname:"Tnk",slug:"suriyaprakash-tnk",fullName:"Suriyaprakash Tnk"}]}],onlineFirstChaptersFilter:{topicId:"219",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81126",title:"Antituberculosis Drug Repurposing: A New Hope for Tackling Multi-Challenging TB in Timely Manner",slug:"antituberculosis-drug-repurposing-a-new-hope-for-tackling-multi-challenging-tb-in-timely-manner",totalDownloads:30,totalDimensionsCites:0,doi:"10.5772/intechopen.101642",abstract:"Tuberculosis still stands as the world’s leading infectious disease as 1/4th of the world’s population harbors Latent TB infection (LTBI) > 10 million develops active TB and ~ 1.5 million people die per year. Approximately 4,65,000 people fell ill with multidrug or rifampicin-resistant tuberculosis (MDR/RR-TB)/year. This deadly TB scenario demands new TB drug regimens to tackle global infection reservoir, and worldwide spread of drug resistance and DS TB. Successful entry of single new drug into market is much complicated mission owing to time, cost, efficacy, and safety issues. Therefore, drug repurposing seems one reliable hope to meet the challenges of modern TB drug discovery timely, as it starts with examining market acclaimed drugs against other diseases for their efficacies against tuberculosis avoiding several lengthy and costly steps required for new molecules. Several drugs have been identified, which show potential for TB treatment. There is need for careful consideration of various trial designs to ensure that TB phase III trials are initiated for fruitful development of new TB treatment regimens. TB drug repurposing will not only give fast track novel drugs but will also serve to identify new targets for future development in cost-effective manner.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Shahnawaz Majeed, Safiya Mehraj and Zahoor Ahmad"},{id:"80848",title:"High-Throughput Screening for Drug Discovery toward Infectious Diseases: Options and Challenges",slug:"high-throughput-screening-for-drug-discovery-toward-infectious-diseases-options-and-challenges",totalDownloads:34,totalDimensionsCites:0,doi:"10.5772/intechopen.102936",abstract:"The increase in the number of antibiotic-resistant microbial strains makes it evident to discover and develop newer efficacious anti-infective drugs. High-throughput screening (HTS) is a robust technology that plays a crucial role in identifying novel anti-infective lead compounds. This chapter briefly explains the role of virtual HTS (vHTS) and HTS technologies in lead identification using various categories of chemical libraries through structure-based drug design, ligand-based drug design, in vitro cell-based assay, and biochemical assay approaches involved in the process of drug design and discovery. The chapter also gives an insightful survey of the technologies such as fluorescence, luminescence, and atomic absorbance used for the detection of biological responses in the HTS bioassays. Applications of HTS, reverse pharmacology, current challenges, and future perspectives of HTS in the pharmaceutical and biotechnology industry are discussed in the context of anti-infective drug design, discovery, and development.",book:{id:"10234",title:"High-Throughput Screening for Drug Discovery",coverURL:"https://cdn.intechopen.com/books/images_new/10234.jpg"},signatures:"Ankur Gupta, Swatantra Kumar, Vimal K. Maurya, Bipin Puri and Shailendra K. Saxena"},{id:"80532",title:"Recent Progress in Drug Repurposing Using Protein Variants and Amino Acids in Disease Phenotypes/Disorders",slug:"recent-progress-in-drug-repurposing-using-protein-variants-and-amino-acids-in-disease-phenotypes-dis",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.102571",abstract:"Life is constituted of large group of macromolecule, functional and structural called “Protein,” made of amino acids (AA), and linked with peptide bonds with specific protein unique sequences. Variations in proteins are thought to have diverse effects with consequences on structure, stability, interactions, pH, enzymatic activity, abundance and other properties. Variants can be of genetic origin or it could occur de novo at the post-translational protein level. The sequence of amino acids defines protein structure and functions. Protein is involved in several critical functions like the physical cell-cell communication. Breakthrough in molecular science has shown that, to develop drugs for managing a disease-associated variations requires understanding of consequences of variants on the function of the affected protein and the impact on the pathways, in which protein is involved. Using biophysical/bioinformatics methods, immense amount of variation data generated is handled-connected to disease phenotypes. Obviously, there remain continuous needs for the combinations of genetic probing methods/bioinformatics, to predict single-nucleotide variations (SNV), for effective rational drug design that would embrace naturally occurring bioactive components of plant origin, towards the effective management of disease phenotype emanating from protein and amino acid variations. This, well thought out and synchronized concept, remains a way forward.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Michael P. Okoh and Lukman A. Alli"},{id:"80170",title:"Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology",slug:"role-of-activated-cdc42-associated-kinase-1-ack1-tnk2-inhibitors-in-precision-oncology",totalDownloads:56,totalDimensionsCites:0,doi:"10.5772/intechopen.102343",abstract:"Activated Cdc42-associated kinase 1 (ACK1) is an intracellular non-receptor tyrosine kinase referred to as TNK2, which is considered as an oncogene and therapeutic target in various cancers including breast cancer, non-small-cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and many others. Oncogenic non-receptor tyrosine kinase mutations occur either due to point mutations, duplications or insertions and deletions, or by involving in the development of a fusion gene resulting from a chromosomal rearrangement. ACK1 is involved with multiple signaling pathways of tumor progression. With these signaling networks, ACK1 participates in cell survival, invasion, migration, and tumorigenesis that are strongly related to the prognosis and clinicopathology of cancers. Previous studies predicted that ACK1 is a carcinogenic factor and blockage of ACK1 inhibits cancer cell survival, proliferation, migration, and radiation resistance. FDA has approved many multi-kinase inhibitors as therapeutic drugs that show good inhibitory activity not against ACK1 but also towards multiple targets. As ACK1 is a key target for other neurological diseases, inflammation, and immunological diseases also, so the studies on these inhibitors not only provide potential strategies for the treatment of cancers that require simultaneous targeting of multiple targets but also can be used in drug repurposing for other diseases.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Ruby Srivastava"},{id:"79784",title:"Breast Cancer Drug Repurposing a Tool for a Challenging Disease",slug:"breast-cancer-drug-repurposing-a-tool-for-a-challenging-disease",totalDownloads:100,totalDimensionsCites:0,doi:"10.5772/intechopen.101378",abstract:"Drug repurposing is one of the best strategy for drug discovery. There are several examples where drug repurposing has revolutionized the drug development process, such as metformin developed for diabetes and is now employed in polycystic ovarian syndrome. Drug repurposing against breast cancer is currently a hot topic to look upon. With the continued rise in breast cancer cases, there is a dire need for new therapies that can tackle it in a better way. There is a rise of resistance to current therapies, so drug repurposing might produce some lead candidates that may be promising to treat breast cancer. We will highlight the breast cancer molecular targets, currently available drugs, problems with current therapy, and some examples that might be promising to treat it.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Jonaid Ahmad Malik, Rafia Jan, Sakeel Ahmed and Sirajudheen Anwar"},{id:"79878",title:"Evaluation of Drug Repositioning by Molecular Docking of Pharmaceutical Resources to Identification of Potential SARS-CoV-2 Viral Inhibitors",slug:"evaluation-of-drug-repositioning-by-molecular-docking-of-pharmaceutical-resources-to-identification-",totalDownloads:106,totalDimensionsCites:0,doi:"10.5772/intechopen.101395",abstract:"Unfortunately, to date, there is no approved specific antiviral drug treatment against COVID-19. Due to the costly and time-consuming nature of the de novo drug discovery and development process, in recent days, the computational drug repositioning method has been highly regarded for accelerating the drug-discovery process. The selection of drug target molecule(s), preparation of an approved therapeutics agent library, and in silico evaluation of their affinity to the subjected target(s) are the main steps of a molecular docking-based drug repositioning process, which is the most common computational drug re-tasking process. In this chapter, after a review on origin, pathophysiology, molecular biology, and drug development strategies against COVID-19, recent advances, challenges as well as the future perspective of molecular docking-based drug repositioning for COVID-19 are discussed. Furthermore, as a case study, the molecular docking-based drug repurposing process was planned to screen the 3CLpro inhibitor(s) among the nine Food and Drug Administration (FDA)-approved antiviral protease inhibitors. The results demonstrated that Fosamprenavir had the highest binding affinity to 3CLpro and can be considered for more in silico, in vitro, and in vivo evaluations as an effective repurposed anti-COVID-19 drug.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Fatemeh Hosseini, Mehrdad Azin, Hamideh Ofoghi and Tahereh Alinejad"}],onlineFirstChaptersTotal:20},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,annualVolume:11415,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. 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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, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for 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:"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:"Beijing University of Technology",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:"Lakhno Igor Victorovich 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.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of 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 a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), 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 DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. 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: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{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:"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. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 15th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:286,numberOfPublishedBooks:27,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. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). 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. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/347303",hash:"",query:{},params:{id:"347303"},fullPath:"/profiles/347303",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)}()