\r\n\tThe purpose of the book is to bring together the latest knowledge about genetic diversity by presenting the studies of some of the scientists who are engaged in development of new tools and ideas used to reveal genetic diversity, often from very different perspectives. The book should prove useful to students, researchers and experts in the area of biology, medicine and agriculture.
",isbn:"978-1-80356-945-1",printIsbn:"978-1-80356-944-4",pdfIsbn:"978-1-80356-946-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"0b1e679fcacdec2448603a66df71ccc7",bookSignature:"Prof. Mahmut Çalışkan and Dr. Sevcan Aydin",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11643.jpg",keywords:"PCR Based Methods, Protein Based Methods, Sequencing, Conservation of Genetic Resources, Natural Variation, Molecular Markers, Genetic Manipulation in Animals, Resistance to Disease, Genetic Manipulation in Plants, Use of Microorganisms in Biotechnology, Genetic Differentiation, Gene Therapy and Gene Editing",numberOfDownloads:13,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Professor of genetics and molecular biology and Head of Biotechnology division at İstanbul University in Turkey whose main research areas include plant molecular genetics, microbial biotechnology and characterization and biotechnological use of halophilic archaeal strains.",coeditorOneBiosketch:"Associate Professor of Biotechnology Division in Department of Biology at Istanbul University in Turkey whose main research areas include genetics, environmental biotechnology and bioengineering.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"51528",title:"Prof.",name:"Mahmut",middleName:null,surname:"Çalışkan",slug:"mahmut-caliskan",fullName:"Mahmut Çalışkan",profilePictureURL:"https://mts.intechopen.com/storage/users/51528/images/system/51528.png",biography:"Mahmut Çalışkan is a Professor of Genetics and Molecular Biology in the Department of Biology, Biotechnology Division, Istanbul University, Turkey. He obtained a BSc from Middle East Technical University, Ankara, and a Ph.D. from the University of Leeds, England. His main research areas include the role of germin gene products during early plant development, analysis of genetic variation, polymorphisms, and the characterization and biotechnological use of halophilic archaea.",institutionString:"Istanbul University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"8",institution:{name:"Istanbul University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:{id:"462767",title:"Dr.",name:"Sevcan",middleName:null,surname:"Aydin",slug:"sevcan-aydin",fullName:"Sevcan Aydin",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003QRfRpQAL/Profile_Picture_2022-03-24T08:49:06.jpg",biography:"Sevcan Aydın is an Associate Professor of Biotechnology Division in Department of Biology at Istanbul University in Türkiye. She obtained her bachelor's degree from Biology Department of Ege University. She obtained her Ph.D. in Biotechnology Programme of Istanbul Technical University. 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It facilitates the investigation and understanding of a system as a whole, not only its single components. For this, first the networks need to be constructed and then investigated employing different analysis or modeling techniques. According to the applied methodological approaches to analyze these networks, one may distinguish cellular network models for signal transduction, gene regulation and metabolism. The network constructions based on information are compiled from databases and are assembled in an automated way often followed by manual refinement. Network-based models have been applied to study the cellular mechanisms of a large variety of diseases elucidating, for example, tumor growth, malfunctioning of the differentiation of immune cells, or identifying drug targets of invasive pathogens [1, 2]. To find drug targets for the treatment of malaria, metabolic and signaling networks have been constructed and intensively investigated. This chapter will introduce the reader into the basic principles of constructing and applying such cellular networks. It then leads through the application of these systems biology approaches to predict drug targets followed by a small section exemplarily showing an experimental validation for these predictions.
Proteins are involved in all cellular functions. These cellular processes can be put up as cellular networks, which describe associations among these proteins and other cellular compounds such as metabolites and nucleic acids. These cellular networks can conceptually be divided into three distinct parts: the cell signaling, the transcriptional regulatory network, and the metabolic network. The best observed and modeled network is the metabolic network while the complex system of signal transduction is rather captured statistically investigating the experimental information about proteins and their expressed genes of network models basing on protein-protein interactions [3]. The transcriptional regulatory network links transcriptional regulators to their target genes [4]. The simplest form of a network is a network represented by an undirected graph
Graphical view of a metabolic network model as a bipartite graph consisting of two disjoint sets of nodes (reactions and metabolites). This network consists of three reactions (R1, R2 and R3) and six metabolites (A, B, C, D, E, F). R1 is a reversible reaction, the other reactions are irreversible.
R1: | A | ⇔ | B |
R2: | 2 B + C | → | E + F |
R3: | 2 E | → | B + D |
The stoichiometric matrix or the adjacency matrix containing stoichiometric coefficients of each reaction equation is
where the rows correspond to metabolites A, B, C, D, E, and F, and the columns correspond to reactions R1, R2, and R3, respectively. R1 is a reversible reaction. Metabolic networks for
Several computational techniques have been developed to identify essential genes and drug targets
The diameter of a network is the largest distance of all shortest paths between two nodes (reactions, signaling molecules) in the network. The density of a network is the ratio of the edges (links, connections) between two reactions divided by all possible edges of all reactions. These two properties can be used to determine the robustness of a network. In recent studies, a reaction was said to be essential if the mutated or targeted network showed a larger diameter after removing the reaction [12, 13].
Networks can be distinguished by their degree distributions where the degree of a node
Degree distribution of the metabolic network of
The clustering coefficient is used to estimate the local density of links (edges) in the network. It describes the connectedness among neighbors and helps to estimate the probability of local alternative paths of signaling or metabolic fluxes (e.g., after targeting). The clustering coefficient of a node
Illustration of the concepts of the topology features. Circles represent metabolites, rectangles reactions, arrows directions of the metabolic flux, lines represent links between two neighboring reactions and dark rectangles represent the investigated reactions. (a) The observed reaction is a chokepoint because it is the only reaction consuming the upstream metabolite. (b) The metabolic network in a reaction-pair representation for computing the clustering coefficient. The observed reaction has three neighbors (degree of 3) and there are two links among these neighbors. Therefore, the clustering coefficient for this observed reaction is 1/3. (c) Graphical illustration of the way to compute producibility of the observed reaction from its substrates (S) to its products (P). Possible alternative pathways to consume substrates S for producing products P are represented by dashed arrows. The percentage of the products that can be produced from the substrates is the producibility of the observed reaction.
Descriptors for
In metabolic networks, Samal
A reaction is determined to be potentially essential when basically the mutated network cannot yield the products of the reaction from upstream substrates of the reaction using other pathways linking the substrates to the products (see Figure 3). The percentage of the products that can be produced from the substrates, the so-called “producibility,” can be used to examine the essentiality of the observed reaction [13].
The concept of choke points and load points was successfully applied to estimate the essentiality of an enzyme in
Protein-protein interactions were inferred by a high-throughput method (yeast-2-hybrid) and assembled for a signaling network of
Recently, Bhattacharyya and Chakrabarti analyzed a large-scale protein-protein interaction network of
Interactions between the human host and the parasite have been intensively studied [11–13, 33]. The comparison of several reconstructed network models has been performed to find the best suitable reconstruction for detecting drug targets
Chen
Flux balance analysis (FBA) is a computational approach to estimate the quantitative flux of metabolites through a mechanistic model of metabolism. Thereby, it is possible to predict the growth rate of an organism or the rate of production of an important metabolite [9, 34–36]. Biochemical stoichiometric equations are used to assemble a set of constraints to limit the feasible search space. The idea is that, at equilibrium, production and consumption of internal metabolites are balanced. This leads to a large set of equations in which the net production flux equals the net consumption flux for each internal metabolite. Additionally, allowable fluxes of any reaction are bounded at plausible maximum and minimum fluxes. Bounds may also be taken from the literature. These balances and bounds define the space of allowable flux distributions of a system, that is, the allowed combinations of fluxes for each reaction. To get a phenotype or modeling prediction from these constraints, an optimization criterion is put up. For example, in the case of predicting growth, the objective is to optimize biomass production which is the rate at which metabolic compounds are converted into the physiological portions of biomass constituents most importantly of nucleic acids, amino acids and lipids. Together with the constraints, this is mathematically formulated as a system of linear equations which is solved using linear programming based programs. Flux variability and knockout simulations are analyzed to detect potential drug targets whose absence reduces the biomass production and hence viability of the parasite in the host cell. By simulating a reconstructed metabolic network of an organism of interest, first a “wildtype” model is investigated and the growth rate of the wildtype under specific bounds (or conditions) obtained. Performing a single gene (or reaction) knockout/deletion under the same condition by limiting its corresponding fluxes to zero (knockout simulation), the fluxes are calculated simulating an organism effected to a drug (targeting the deleted enzyme) and the growth rate is compared to the wildtype. A knocked out gene (or reaction) is predicted to be essential under the given condition if the mutant model yields a much lower growth rate compared to the wildtype. Flux balance analysis is a widely used and well-established technique to assess the essentiality of genes and hence potential drug targets [9, 34–36]. The beauty of this approach is that it does not depend on specific enzymatic parameters for each enzyme like their Michaelis Menten constants, etc., but are rather basing on simple stoichiometric equations. To some extent, the only experimental parameters are the boundary conditions. The drawback is that often several solutions can come out which are mathematically equally good, but physiologically very different leading to follow-up analyses of each of these solutions. Nevertheless, the approach was used for several genome-scale metabolic network constructions, followed by flux simulations of the inner metabolites of
Let
where
where
FBA has been widely used to predict essential genes of the human malaria parasite
Recently, Phaiphinit et al. reconstructed the metabolic network of
The workflow to identify drug targets by the comparison of treated and untreated conditions. First,
FBA was used to get the flux distributions for the untreated and the treated conditions. For the untreated condition, the objective was to maximize the production rate of biomass according to Ref. [36], including the Na+/K+ ratio based potential at the ATPase, which plays an important role for the homeostasis of red blood cells [43, 44]. In the treated condition, the drug usually inhibits the detoxification process of the parasite harming the parasite due to the toxicity of free heme. Thus, during the treated condition, the (toxic) flux of heme production should be an additional objective to ensure that the toxic flux is not zero when identifying reactions or enzymes to be blocked during the treatment. The flux distributions of both models were then compared to obtain a list of candidate targets by the criteria that the reactions with zero fluxes in the treated condition but non-zero fluxes in the untreated condition could be potential targets for inhibiting heme detoxification.
With this method, 23 enzymes were identified as candidate targets, which mostly were in pyruvate metabolism and the citrate cycle. The optimal set of multiple targets for blocking the detoxification was a set of a heme ligase, adenosine transporter, myo-inositol 1-phosphate synthase, ferrodoxim reductase-like protein, and the guanine transporter. Purine transporters have been known as the major route of purine into the parasitized red blood cell. In the development of anti-malarial drugs, inhibitors targeting purine transport are of pharmaceutical interest and are investigated. Likewise, adenosine transport and its inhibitor have been studied in infected and uninfected human erythrocytes recently [45]. In summary, this shows an efficient way to identify useful target combinations in the development of novel antimalarial drugs [35].
Typically, after the computational network analysis, a list of potential drug targets is assembled and needs to be validated experimentally. Exemplarily, in one study of a topological network analysis, 22 potential targets were proposed [26]. Using a refined network comprising also the host enzymes led to a refined set of the five potential drug targets (glutamyl–tRNA(gln) amidotransferase, hydroxyethylthiazole kinase, deoxyribose–phosphate aldolase, pseudouridylate synthase, and deoxyhypusine synthase) [46]. The next step was to find effective inhibitors to block these enzymes. Many reported inhibitors can be collected from databases like the Brenda Enzyme database [47], Drugbank [48], and from companies like Sigma (
Even though the number of deaths caused by malaria has diminished considerably, it is still a challenge to treat the effected patients and clear off the pathogen after infection. In particular, there are increasingly more strains getting resistant against common treatments, and hence there is a striking demand to find new targets for therapy.
The computational approaches introduced here show some convincing results. However, it needs to be shown that these predictions are experimentally confirmed and finally make their way from the bench to the bedside.
Various techniques of network-based analyses to identify potential drug targets of
Even though all these presented concepts have the very same aim to find a target, their results are quite heterogeneous lists of different predicted drug targets, some of them validated by experimental assays. As a future aspect, a data and method integration needs to be performed leading to a
Chagas disease (CD), the parasitic infection caused by the kinetoplastid protozoan
It is alarming that 6–7 million people are estimated to have CD worldwide, with
CD represents economic losses in excess of $1.2 billion/year to endemic countries in South America, in addition to more than $7 billion a year at global levels [21], including treatment and loss of productivity. Since no proven effective and approved vaccines are available for this disease, chemotherapy represents the only therapeutic intervention, as well as an important way to control them.
CD etiological treatment is directed according to the phase and clinical presentation of the disease, which is mandatory in the acute phase, congenital cases, or reactivation due to immunosuppression. In the chronic phase, the trypanocidal treatment is indicated in children and adolescents, recent infection, and women of childbearing age [22].
Although CD was discovered and is studied for over a century [14], the etiologic treatment is still based on solely two drugs (Figure 1): the nitrofuran derivative nifurtimox (NFX; Lampit®, Bayer; 5-nitrofuran(3-methyl-4-(5′-nitrofurfurylideneamine)tetrahydro-4H-1,4-tiazine-1,1-dioxide), and the 2-nitromidazole benznidazole (BZ; LAFEPE; N-benzyl-2-nitroimidazole-acetamide) [23]. Both NFX and BZ were shown to produce remarkable ultrastructural alterations in mammal cells and tissues [24, 25], which were apparently more pronounced in NFX-treated animals [26]. Therefore, experimental chemotherapy studies approaching parasites as
Molecular structures of the nitroheterocyclic drugs employed in the treatment of Chagas disease: the 2-nitroimidazole benznidazole (A) and the 5-nitrofuran nifurtimox (B).
The CD therapeutics remain unsatisfactory, as they are associated with adverse effects [30, 31, 32], affecting 84.8 and 95.2% of patients treated with BZ and NFX, respectively [33], which may be severe, leading to the irreversible suspension of therapy in CD, in ≈20% [34, 35], ≈30% [36, 37], 41.5% [38], and up to 50% of the cases [39, 40]. Treatment suspension using NFX was reported in 43.8% of patients [33]. In an early study based on small samples, NFX was reported to be associated to definitive treatment interruption in 75% of patients [38]. Nevertheless, treatment intolerance was reported at similar levels with the use of the two drugs, approached by the same team [34, 35], but adverse effects, including neuropsychiatric events, may be more frequently associated to NFX [33]. In addition, it was reported that among patients who had discontinued BZ treatment and were treated with NFX, 12.3% also developed adverse effects that required definitive discontinuation of therapy [39]. Nevertheless, NFX was reported to be safe as a second-line therapy in patients who discontinued BZ [41].
Most CD patients are not treated because of the insufficient diagnosis and low cure rates observed in chronically infected patients [42], although treatment may diminish the disease progression and cardiovascular events [43, 44]. In addition, the CD treatment accomplishes only a parasitological cure, and a clinical cure is hardly proved [43, 45]. Whereas the
As the dormancy state of
An important study [63] approached the persistent parasite elimination, but the use of higher BZ doses might pose higher risks for patients. In this regard, the polyamine and thiol synthesis
Besides considerable severe adverse effects, one of the greatest problems of CD therapeutics is the selection of resistant parasites, impairing its effectivity, therefore causing refractory cases. BZ and NFX resistance is readily developed
Despite significant time and resources investments by innumerous research institutions over the world, only a few therapeutic candidates advanced the pipeline to treat neglected diseases such as CD [67]. It is alarming that it usually takes over 10 years to develop new drugs, whereas resistant parasites are rapidly selected. Also, there are naturally resistant
Oxidative stress is a central phenomenon involved in aging, cancer, transmissible or infectious diseases, including COVID-19 [72], nontransmissible chronic conditions, such as metabolic diseases, autoimmune and degenerative disorders, inflammation, metal poisoning, etc. [73, 74, 75], produced by the imbalance on the production/uptake of oxidant/antioxidant species [76].
A plethora of antioxidant defenses evolved in order to balance the redox homeostasis [76, 77]. Oxidant species such as superoxide (O2•−) and hydrogen peroxide (H2O2) are detoxified by SOD and catalase, respectively. Most cells rely also on the peptide glutathione (GSH), able to chelate reactive oxidant species (ROS) via cysteine sulfhydryl (SH) group and function as substrate for enzymes including GSH reductase and GSH peroxidase [78].
Although most of these processes are evolutionary conserved, some of the antioxidant defenses pathways differ between mammals and pathogens, therefore comprise potential chemotherapy targets. Contrary to mammals, GSH in trypanosomatid parasites mostly takes part in the adduct with the polyamine spermidine, forming
Metabolomics and gene expression studies [81] reveal the participation of both GSH and the spermidine synthesis pathway, indicating the participation of trypanothione, in the regulation of redox metabolism in trypanosomatids. GSH is very relevant not only in oxi-reductive homeostasis, as this molecule is also related to detoxification and resistance to different drugs/xenobiotics in tumor cells [82, 83] binding to drugs that are extruded via multidrug resistance transporters [84]. TSH binding to NFX and BZ is involved in the detoxication of these trypanocides [85, 86]. Therefore, glutathione/trypanothione can promote the action/reverse resistance to different drugs.
Interestingly, polyamine play pivotal roles in parasite cells [91, 92], including
Parasitic diseases such as CD are correlated to oxidative stress [97, 98], associated to triggered chronic inflammatory reactions [99, 100]. Endogenous oxidative stress may be produced by cell organelles, mainly mitochondria [101, 102]. The CD myocarditis is characterized by intense oxidative stress due both to inflammatory response associated to neutrophils and macrophages NADPH oxidase (Nox) activity and the macrophage superoxide produced by Nox2 is required for parasite control in early infection [103]. The mitochondrial ROS produced by cardiomyocytes plays a relevant role in intracellular oxidative stress and inflammation, causing myocardium tissue damage [104, 105, 106]. These events are not independent since mitochondrial ROS may trigger proinflammatory cytokines via NFkB and PARP/PAR pathways [107], and the mitochondrial MnSOD activity may revert much of the inflammatory foci and necrosis [105], and ineffective antioxidant defense is associated to oxidative stress [108]. Exosome or extracellular vesicles liberation may also contribute to inflammation and oxidative stress [107, 109]. The oxidative stress is also involved in neurodegeneration in both cardiac and gastrointestinal tissues [110]. The chronic oxidative stress in the nervous tissue is associated to cognitive deficit, which can be reversed by BZ treatment [111].
Thus, the use of adjuvant antioxidant agents may ameliorate the cardiac pathogenesis [107, 112, 113]. Interestingly, vitamin C, widely considered antioxidant, can at high concentrations also function as a prooxidant, undergoing pH-dependent autoxidation, leading to H2O2 formation [114, 115]. In CD models, ascorbic acid can also reduce parasitemia, promote BZ action, and enhance animal survival in murine infection [116, 117].
ROS production comprises a well-known microbicidal immune effector mechanism [118]; therefore parasite borne antioxidant systems are not only virulence factors [119]. Besides the parasiticidal activity, ROS may function as signaling molecules promoting parasite proliferation. As in the Paracelsus adage, “The dose makes the poison” (Latin:
Numerous therapeutic strategies exploit redox systems [124], including protozoal diseases [125], such as CD [126]. Therefore, antioxidant systems including SOD, trypanothione, and enzymes action on this glutathione-spermidine adduct (
Up to 2% of the O2 reaching the mitochondrial matrix is converted to O2•− (superoxide anions) forming H2O2 via SOD [149]. Like mammalian cells,
Because of the prooxidant effects of antiparasitic drugs [126, 153, 154, 155], ROS detoxifying systems may comprise valuable scape mechanisms from pharmaceutical intervention [156] and programmed cell death triggered by mitochondrial O2•− [157].
The prooxidant capacity of both NFX and BZ, particularly in the former, is due to redox cycling with the production of O2•− [126, 158, 159, 160]. Superoxide may be not produced by BZ in the parasite, but in the host cell [161]. Therefore, FeSOD is linked to BZ resistance in
Sirtuins are a highly conserved family of enzymes that deacetylate lysine residues on histone and non-histone proteins, using NAD+ as a cosubstrate, regulating cellular antioxidant/Redox mechanisms [172, 173]. It is noteworthy that SIRT3, 4, and 5 are found in the mitochondrial matrix [174]. As cardiomyocyte mitochondrial dysfunction plays a central role in chagasic myocarditis (
Selenium and selenium-containing compounds show beneficial effects both in murine [178, 179, 180] and human
This activity maybe largely dependent on redox regulation as this inflammatory infection is associated with intense oxidative stress, and selenium may be antioxidant [187] and anti-inflammatory [188], as well as catalyze hydrogen peroxide (H2O2) reduction [189], therefore possibly diminishing the oxidative stress in infected cardiomyocytes, by impairing the Fenton reaction in the presence of iron.
The combination of different drugs may pose the advantage of supra-additive effects, which may be synergistic, in parasite models such as
The identification of drug combinations with multiple targets can lead to the use of novel multitarget mechanisms able to cope with the challenge of multigenic diseases [194] and/or chronic infections with complex pathophysiology. It is noteworthy that the pharmaceutical properties of the combination may be absent in the components alone [195], generating the innovative concept or science field termed polypharmacology with numerous applications on drug repurposing [196] and CD [197]. As the philosopher Aristotle (384–322 B.C.) stated: “The whole is greater than the sum of its parts.”1
Furthermore, drug combinations are largely employed for preventing drug resistance [198, 199, 200, 201, 202, 203, 204]. However, this strategy is not constantly successful as the reports of resistance to the sulfadoxine-pyrimethamine combination began in the same year this antimalarial regimen entered the clinic [205]. Similarly, the discovery of artemisinin (ART) costed Youyou Tu over 30 years of hard work [206] and was worthy a Nobel Prize, but
Approaching repositioned drugs with available pharmacokinetic and toxicological properties can shorten the long and expensive path between
Drug repositioning maybe a promising approach in CD [214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227]. Similarly, drug combinations may be instrumental in CD [197, 228, 229, 230, 231, 232, 233], and both strategies may be employed and associated [214, 234, 235, 236]. Furthermore, drug combinations can increase success of drug repositioning [237]. In addition, it was accurately hypothesized that the combined use of repurposed drugs with BZ could be more efficacious than BZ alone [238].
Disulfiram (DS, 1,1′-disulfanediylbis(N,N-diethylmethanethioamide) also termed tetraethylthiuram disulfide; CAS no. 97-77-8; Molecular Formula: C10H20N2S4), a repositioned drug used in alcoholism and marketed as Antabuse® (Figure 2), was approved for medical use over 70 years ago and is widely used since then [239, 240].
Molecular structures of disulfiram (A) and sodium diethyldithiocarbamate (B).
At the very beginning, the discovery of thiocarbamates and its derivatives was serendipitous and showed clear signs of versatile perspectives that unequivocally culminated in the present promising repurposing strategies for both pharmaceutical and industrial applications [241, 242].
In the 1930s and 1940s, dithiocarbamates such as dimethyldithiocarbamates and diethyldithiocarbamates were used as pesticides against fungal pathogens on different crops [243], besides biocides in household products [244].
The industry plant physician E. E. Williams in 1937 observed that workers using tetramethylthiuram monosulfide and disulfide to facilitate the rubber vulcanization became alcohol-intolerant and quit consuming alcoholic beverages. The DSF-induced alcohol aversion was described in 1948 [245]. At that time, DSF was approached as a vermicide and employed as an ointment to treat scabies.
Afterward, besides alcoholism, DSF started to be studied for heavy metal poisoning, cancer [246, 247, 248, 249], HIV [243, 250], as well as cocaine dependence, pathological gambling, and other psychiatric disorders [239] and other form of addiction, for example, the d-methamphetamine abuse [251]. Further tests are being performed focusing applications such as Alzheimer’s disease [252], Lyme disease and babesiosis [253], tuberculosis [254], non-tuberculous mycobacteria infections [255], giardiasis [256], amoebiasis [257], obesity [258] and to revert drug resistance in different types of cancer [259, 260, 261], tuberculosis [262] bacterial infections [263], mycosis [264], giardiasis [265], etc. The repositioning of low-cost drugs such as DS is considered a “salvation” for global healthcare system [266].
Sodium diethylcarbamodithioate (Figure 2) (DETC also known as sodium (diethylcarbamothioyl)sulfanide; CAS no. 148-18-5; Molecular Formula: C5H11NS2.Na) is the first derivative of DSF, involved in many of the biological activities of the latter.
Seemingly DETC is less toxic than aspirin [243], widely used, and well tolerated in humans [267] for decades being used up to 800 mg/twice/week, with no adverse effects [268]. DETC also known as Imuthiol or Dithiocarb was used as immunomodulator with good results on AIDS patients [269, 270] and was clinically employed in chronic bronchitis, rheumatoid arthritis, tuberculosis, and chronic infection [271].
In a seminal report on its antiparasitic activity, DETC was demonstrated to be leishmanicidal [272]. Afterward, novel delivery systems were developed to optimize the leishmanicidal activity of DETC [273, 274, 275]. In this regard, novel drug delivery systems are also developed for DSF [276]. The data obtained on Leishmania amazonensis motivated us to move to CD, employing the repositioned drug DSF combined to the drug of first choice BZ. Tests on NFX are in progress.
It is worth remembering that CD pathophysiology is associated with oxidative stress (
Both DSF and DETC have antiparasitic activity on
In our study, the DSF-BZ combination is promising since the antagonism of SOD activity can enhance oxidative stress in cancer cells [249] and
Putative mechanisms of action of disulfiram (DSF) or diethyldithiocarbamate (DETC) in combination with trypanocides in
CD etiological therapy is often associated to severe adverse effects caused by the highly toxic drugs (
DSF/DETC have neuroprotective [285], hepatoprotective [277], and nephroprotective [286] and even radioprotective [287, 288] activity. These protective effects may be beneficial in the treatment of parasitic diseases, because in the treatment of experimental infection by
Thus, the development of low-toxicity therapies may be expected, as DSF may have a protective action against the toxic effects of drugs such as cyclophosphamide [290], ifosfamide [291], N-nitrosodimethylamine [292], isoniazid [293] and the toxicity of α-naphthylisothiocyanate [294], acetaminophen [295], pyrrolizidines [296], the lethal effects of hypoxia [297], ischemia [298], as well as lead [299], cadmium [300], mercury, and other heavy metals [301]. Thus, DSF combinations can enable the development of safe medicines. Regarding CD, the cardioprotective and antioxidant activities of DSF/DETC as well as atrial neuroprotection [302] are particularly desirable [303, 304, 305, 306]. In addition, DSF is effective as prophylactics in experimental colitis [307].
As drug resistance limits the successful CD therapy, the
DSF [313] affects the redox balance of the cell, to GSH oxidation [314], reducing GSH levels [54] at least in part through the formation of complexes with its different derivatives [312, 315]. DETC can also reduce the GSH/non-protein thiol levels, also leading to the reduction of glutathione peroxidase activities [53, 316].
The combinations tested here may also contribute to resistance reversal, also through DETC-mediated inhibition of Fe-dependent SOD, which is linked to resistance to BZ in
Furthermore, DSF can be used against cancer cells targeting the ubiquitin-proteasome system [317], and the ubiquitin-proteasome pathway is a therapeutic target in
In this way, the strategy based of combinations of the repositioned drugs proposed here can achieve effectiveness, with selectivity and, therefore, safety in the CD treatment and sheds new light on perspectives for new therapeutic strategies.
Translational research in biomedical sciences translates basic research and experimental discoveries into health taking the route from benchtop to bedside. This important field has gained substantial attention and investments in the last two decades [319].
In order to reach a proof of concept on the effectivity of the DSF-BZ combination in human infection, a partnership was established gathering different units of Fiocruz. The present study comprises a translational approach that began with experiments in vitro, on the bench and now reaches the clinical stage at the Evandro Chagas National Institute of Infectious Diseases-Fiocruz, coordinated by the team of the Clinical Research Laboratory of Chagas Disease, with assistance of the Clinical Research platform. Therefore, the phase I/II clinical trial was elaborated (Figure 4) and published recently [320].
Design of the clinical trial for testing the BZ-DSF combination. Reproduced from Ref. [
The use of DSF/DETC combined to BZ in CD treatment comprises a potential innovative therapeutical tool, possibly overcoming adverse reactions and refractory cases. Since these repositioned drugs exert cytoprotective effects, reducing the adverse reactions of many drugs, safe combinations can be potentially identified, leading to the development of well-tolerated medication. Therefore, therapy interruption can be precluded, consequently increasing patient adherence. In addition, as DSF/DETC can inhibit p-glycoprotein activity as well as reduce GSH levels, two molecules involved in drug extrusion from MDR+ parasites, it is reasonable to suppose the combination could eventually revert/downmodulate natural/acquired resistance phenotypes. Thus, treatment may be effective even in refractory cases. We are now approaching the clinical response of chronic phase CD patients. A possible proof of concept may lead to the development of a safe and effective medication, with profound implications in treatment prognosis, presumably improving the quality of life of the patients.
This research was sponsored by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq grant no. 443886/2018-0 to RMS and CNPq grant no. 314717/2020 to MAVS), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Rio de Janeiro (FAPERJ grant no. 211.167/2019 to RMS; FAPERJ grant no. 260475/2021 and 259286/2021 to MAVS and FAPERJ grant no. 204.388/2021 to AMSF) and Fundação Oswaldo Cruz (Fiocruz grant no. 6221125199 to MAVS).
IntechOpen - where academia and industry create content with global impact
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\n\nSara Uhac, COO
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\n\nDr Alex Lazinica
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This study is aimed to focus on proceeding of the most vital metabolic processes namely reserve mobilization, phytohormonal regulation, glyoxylate cycle and respiration process under either stressful or non-stressful conditions that may be led to suggest and conduct the more successful experimental improvements. Seed imbibition triggered the activation of various metabolic processes such as synthesis of hydrolytic enzymes which resulted in hydrolysis of reserve food into simple available form for embryo uptake. Abiotic stresses potentially affect seed germination and seedling establishment through various factors, such as a reduction in water availability, changes in the mobilization of stored reserves, hormonal balance alteration and affecting the structural organization of proteins. Recent strategies for improving seed quality involved classical genetic, molecular biology and invigoration treatments known as priming treatments. 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The importance of these compounds in wine is due to their large effect on the organoleptic attributes of wine. Phenolic compounds play a crucial role in the colour as well as mouthfeel properties of wines. UV-visible spectroscopy appears as a suitable technique for the evaluation of phenolic compounds’ properties and content. The ability of the phenolic ring to absorb UV light and the fact that some of the phenolic substances are coloured compounds, i.e. show absorption features in the visible region, make UV-visible spectroscopy a suitable technique to investigate and quantify grape and wine phenolic compounds. A number of analytical techniques are currently used for phenolic quantification. These include both simpler approaches (spectrophotometric determinations) as well as more complex methodologies such liquid chromatography analysis. Moreover, a number of spectroscopy applications have also been recently reported and are becoming popular within the wine industry. 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To fulfil this gap various techniques are adopted for obtaining high yield pectin from various agro-industrial wastes. This chapter will be focusing on extraction and purification of pectin from various agro-industrial wastes, considered as main environmental pollutants.",book:{id:"8504",slug:"pectins-extraction-purification-characterization-and-applications",title:"Pectins",fullTitle:"Pectins - Extraction, Purification, Characterization and Applications"},signatures:"Erumalla Venkatanagaraju, N. Bharathi, Rachiraju Hema Sindhuja, Rajshree Roy Chowdhury and Yarram Sreelekha",authors:null},{id:"69396",title:"Soybean Amino Acids in Health, Genetics, and Evaluation",slug:"soybean-amino-acids-in-health-genetics-and-evaluation",totalDownloads:1421,totalCrossrefCites:0,totalDimensionsCites:6,abstract:"Soybean is an important source of protein and amino acids for humans and livestock because of its well-balanced amino acid profile. This chapter outlines the strengths and weaknesses of soybean as a complete amino acid source as well as the relative importance of individual amino acids. Special attention is paid to the sulfur-containing amino acids, methionine and cysteine. Breeding and genetic engineering efforts are summarized to highlight previous accomplishments in amino acid improvement and potential avenues for future research. Agronomic properties and processing methods that affect amino acid levels in soybean food and feed are also explained. A brief introduction into current amino acid evaluation techniques is provided. By understanding the complexities of amino acids in soybean, protein quality for humans and livestock can be maximized.",book:{id:"6972",slug:"soybean-for-human-consumption-and-animal-feed",title:"Soybean for Human Consumption and Animal Feed",fullTitle:"Soybean for Human Consumption and Animal Feed"},signatures:"William Monte Singer, Bo Zhang, M.A. Rouf Mian and Haibo Huang",authors:[{id:"308970",title:"Mr.",name:"William",middleName:null,surname:"Singer",slug:"william-singer",fullName:"William Singer"},{id:"309005",title:"Dr.",name:"Bo",middleName:null,surname:"Zhang",slug:"bo-zhang",fullName:"Bo Zhang"},{id:"310776",title:"Dr.",name:"M.A. Rouf",middleName:null,surname:"Mian",slug:"m.a.-rouf-mian",fullName:"M.A. Rouf Mian"},{id:"310777",title:"Dr.",name:"Haibo",middleName:null,surname:"Huang",slug:"haibo-huang",fullName:"Haibo Huang"}]},{id:"56975",title:"Metabolic Processes During Seed Germination",slug:"metabolic-processes-during-seed-germination",totalDownloads:6220,totalCrossrefCites:29,totalDimensionsCites:63,abstract:"Seed germination is crucial stage in plant development and can be considered as a determinant for plant productivity. Physiological and biochemical changes followed by morphological changes during germination are strongly related to seedling survival rate and vegetative growth which consequently affect yield and quality. This study is aimed to focus on proceeding of the most vital metabolic processes namely reserve mobilization, phytohormonal regulation, glyoxylate cycle and respiration process under either stressful or non-stressful conditions that may be led to suggest and conduct the more successful experimental improvements. Seed imbibition triggered the activation of various metabolic processes such as synthesis of hydrolytic enzymes which resulted in hydrolysis of reserve food into simple available form for embryo uptake. Abiotic stresses potentially affect seed germination and seedling establishment through various factors, such as a reduction in water availability, changes in the mobilization of stored reserves, hormonal balance alteration and affecting the structural organization of proteins. Recent strategies for improving seed quality involved classical genetic, molecular biology and invigoration treatments known as priming treatments. H2O2 accumulation and associated oxidative damages together with a decline in antioxidant mechanisms can be regarded as a source of stress that may suppress germination. Seed priming was aimed primarily to control seed hydration by lowering external water potential, or shortening the hydration period.",book:{id:"6096",slug:"advances-in-seed-biology",title:"Seed Biology",fullTitle:"Advances in Seed Biology"},signatures:"Awatif S. Ali and Alaaeldin A. 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These micelles are being extensively studied because of their importance in functional behavior of milk and various milk products. However, the exact structure and nature of these casein micelles are still under debate. These different casein proteins possess different functional properties due to their primary amino acid sequence.",book:{id:"5060",slug:"milk-proteins-from-structure-to-biological-properties-and-health-aspects",title:"Milk Proteins",fullTitle:"Milk Proteins - From Structure to Biological Properties and Health Aspects"},signatures:"Mohd Younus Bhat, Tanveer Ali Dar and Laishram Rajendrakumar\nSingh",authors:[{id:"178323",title:"Dr.",name:"Laishram R",middleName:null,surname:"Singh",slug:"laishram-r-singh",fullName:"Laishram R Singh"},{id:"183444",title:"Mr.",name:"Md. Younus",middleName:null,surname:"Bhat",slug:"md.-younus-bhat",fullName:"Md. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:16,paginationItems:[{id:"82135",title:"Carotenoids in Cassava (Manihot esculenta Crantz)",doi:"10.5772/intechopen.105210",signatures:"Lovina I. Udoh, Josephine U. Agogbua, Eberechi R. Keyagha and Itorobong I. 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Serves as a peer reviewer for biomedical journals. Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. 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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. 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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. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",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. 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For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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