Enzyme kinetics parameters for the kynurenine pathway enzymes.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2246",leadTitle:null,fullTitle:"Global Perspectives on Sustainable Forest Management",title:"Global Perspectives on Sustainable Forest Management",subtitle:null,reviewType:"peer-reviewed",abstract:"This book is dedicated to global perspectives on sustainable forest management. It focuses on a need to move away from purely protective management of forests to innovative approaches for multiple use and management of forest resources. The book is divided into two sections; the first section, with thirteen chapters deals with the forest management aspects while the second section, with five chapters is dedicated to forest utilization.\nThis book will fill the existing gaps in the knowledge about emerging perspectives on sustainable forest management. It will be an interesting and helpful resource to managers, specialists and students in the field of forestry and natural resources management.",isbn:null,printIsbn:"978-953-51-0569-5",pdfIsbn:"978-953-51-5283-5",doi:"10.5772/2634",price:139,priceEur:155,priceUsd:179,slug:"global-perspectives-on-sustainable-forest-management",numberOfPages:316,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"b633fc6fc6a3a8f24dd4c4373fb14cb7",bookSignature:"Okia Clement Akais",publishedDate:"April 25th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2246.jpg",numberOfDownloads:205446,numberOfWosCitations:126,numberOfCrossrefCitations:62,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:183,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:371,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2011",dateEndSecondStepPublish:"May 11th 2011",dateEndThirdStepPublish:"September 15th 2011",dateEndFourthStepPublish:"October 15th 2011",dateEndFifthStepPublish:"February 14th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"119660",title:"Dr.",name:"Dr. Clement A.",middleName:null,surname:"Okia",slug:"dr.-clement-a.-okia",fullName:"Dr. Clement A. 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Rajesh Banu",coverURL:"https://cdn.intechopen.com/books/images_new/6839.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"218539",title:"Dr.",name:"Rajesh Banu",middleName:null,surname:"Jeyakumar",slug:"rajesh-banu-jeyakumar",fullName:"Rajesh Banu Jeyakumar"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11563",leadTitle:null,title:"A Comprehensive Review of the Versatile Dehydration Processes",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tIn general, dehydration is defined as a process of water loss. More specifically, dehydration is a heterogeneous physicochemical process that leads to a decrease in water molecules concentration in some material, and more specifically at the surface of solid material. Dehydration is a reversible, endothermal reaction that happens at the interface of interaction. The most striking property of dehydration is the active involvement of intermediate products in the process of water removal. Dehydration has enormous practical and theoretical significance in various fields, from bio-medical and environmental to materials and physicochemical sciences. Despite that, and the existence of numerous literature data concerning dehydration, which is most frequently described as drying, dehydration is not enough systematically investigated. The critical overview of the available literature data reveals that the main field in up-to-date investigations of dehydration are the following: novel theoretical models of the mechanism of the dehydration process and models developed for describing the kinetics of the dehydration process, non-equilibrium thermodynamics features of the dehydration process, dehydration assisted with different external fields and their effects on the process and kinetics of the dehydration, the effects of the phase-state of adsorbed water on the processes and kinetics of the dehydration, phase, and structural changes in adsorption materials during dehydration and dehydration of specific groups of materials, such as inorganic oxides, crystals- hydrates, zeolites, silicates and clays, polysaccharides, amino acids, peptides, composites, nanocomposites, polymers, hydrogels, aerogels, foods and food products, fruits, vegetables, meats, and biological materials ( tissues, algae, mushrooms, etc.), pharmaceuticals, etc. It is worth mentioning that dehydration of hydrogels, as a specific class of materials, gets more important in the last decade. The proposed book aims to give a comprehensive overview of the up-to-date state-of-the-art in the most relevant topics in dehydration with special emphasis on novel materials and novel methods in mathematical modeling of dehydration’s kinetics, but not limited to them. The author’s contributions in the highlighted potential of novel findings in dehydration processes and their miscellaneous application will be acknowledged.
",isbn:"978-1-83768-141-9",printIsbn:"978-1-83768-140-2",pdfIsbn:"978-1-83768-142-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"91d7853d4e74d161d7a8f5913626cf94",bookSignature:"Ph.D. Jelena Jovanovic",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11563.jpg",keywords:"Mechanism of Dehydration, Phase State, Phase Transformations, Kinetics, Dehydration Isotherms, Enthalpy, Gibb’s Free Energy, Activation Energy, Inorganic Materials, Natural Materials, Composites, Hydrogels",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 24th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Experienced researcher in smart materials, polymers, hydrogels, synthesis, and kinetics, with a BS and MS, focused in Organic Chemistry and Polymers from the Faculty of Technology and Metallurgy, University of Belgrade and a high h index (27).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"447810",title:"Ph.D.",name:"Jelena",middleName:null,surname:"Jovanovic",slug:"jelena-jovanovic",fullName:"Jelena Jovanovic",profilePictureURL:"https://mts.intechopen.com/storage/users/447810/images/system/447810.jpg",biography:"Dr. J. Jovanovic is a research professor at the Institute of General and Physical Chemistry (IOFH) in Belgrade, R. Serbia, as since 2019 and previously she was employed at the University of Belgrade, Faculty of Physical Chemistry during 2005-2019 The main academic and scientific career of Dr. J. Jovanovic is extensive and covers several areas: advanced and smart materials, polymers, polymer composites, carbon composite materials, hydrogels. Synthesis with special emphasis on non-conventional synthesis, e.g. under microwaves, ultrasonic, or cavitation. Green chemistry synthesis and physicochemical processes. Synthesis of various types of hydrogels both under conventional and unconventional conditions. She works extensively on the investigation of the effects of different fields on the reaction kinetics of chemical and physicochemical processes. Hydrogel swelling properties and kinetics, dehydration kinetics, and drug-delivery kinetics using up-to-date and novel methods are extensively involved. The isothermal and non-isothermal kinetics analyses of various physicochemical processes and chemical reactions (adsorption, polymerization, extraction, dehydration). Dr. J. Jovanovic worked on the development of new physicochemical processes and examination of the phase state of sorbent matter.",institutionString:"University of Belgrade",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Belgrade",institutionURL:null,country:{name:"Serbia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"418641",firstName:"Iva",lastName:"Ribic",middleName:null,title:"M.Sc.",imageUrl:"https://mts.intechopen.com/storage/users/418641/images/16830_n.png",email:"iva.r@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Although approximately 1% of tryptophan dietary intake is used for protein synthesis, the rest 99% is metabolized through the 5‐hydroxyindole pathway for the production of melatonin and serotonin, decarboxylated to tryptamine, transaminated to indol‐3‐pyruvic acid, or oxidized by the so‐named kynurenine pathway (KP), for the new synthesis of NAD+ and NADP+ (Figure 1) [1–3].
Tryptophan catabolism occurs by different pathways. Ninety‐five percent of the dietary uptake of tryptophan is catabolized mainly by the kynurenine pathway. About 3% is decarboxylated to tryptamine or transaminated to indol‐3‐pyruvic acid, 1% is intended for serotonin and melatonin synthesis, and resting 1% is for protein synthesis.
The KP degrades over 95% of whole tryptophan intake; its rate‐limiting enzymes, tryptophan 2,3‐dioxygenase (TDO), and indoleamine 2,3‐dioxygenase (IDO), catalyze the cleavage of the tryptophan pyrrole ring to produce N‐formylkynurenine [1, 4]. Among mammals, TDO is mainly expressed in liver and only uses l‐tryptophan as a specific substrate; instead of that, IDO is expressed in extrahepatic tissues, such as brain, lung, kidney, and immune cells [1, 4]. Furthermore, IDO’s substrate span is wider than TDO’s, being d‐ or l‐tryptophan, d‐ or l‐hydroxytryptophan, tryptamine, serotonin, and melatonine available for the catalytic activity of IDO [5]. An IDO isoenzyme has been reported, IDO2 is expressed in the murine kidney, liver, and reproductive system, and the gene encoding IDO2 is adjacent to the IDO gene and has similar affinity for substrates than IDO [6, 7]. N‐formylkynurenine is transformed to l‐kynurenine (l‐kyn) by the arylformidase (AFMID); kynurenine aminotransferases (KAT I, KAT II), and kynureninase (KYNU), with pyridoxal‐5′‐phosphate as a cofactor, as well as kynurenine monooxygenase (KMO), which uses FAD as a cofactor, transform l‐kyn into kynurenic acid (Kyna), anthranilic acid (AA), or 3‐hydroxykynurenine (3‐HK), respectively [8–10]. KMO is located in mitochondrial outer membrane and it has been shown to have high affinity by the substrate suggesting that KMO metabolizes more l‐kyn than other enzymes [11]. KATs and KYNU can also use 3‐HK as a substrate to produce xanthurenic acid (Xanth) or 3‐hydroxyanthranilic acid (3HAA) [8, 12]. Oxidation of 3HAA by the 3HAA dioxygenase (3HAADO) produces 2‐amino‐3‐carboxymuconate semialdehyde (Acms) which is transformed by non‐enzymatic dehydration into quinolinic acid (Quin), or into picolinic acid (Pic) by the Acms decarboxylase (ACMSD). Finally, Quin phosphoribosyltransferase (QPRT) uses Quin as a substrate for the formation of nicotinamine‐adenine‐mononucleotide (NaMN), the nicotinamine‐adenine‐dinucleotide (NAD+) precursor (Figure 2) [13, 14]. Enzyme kinetics of the whole KP have been determined, giving a wide perspective of the kynurenine pathway and its functionality [13], enzyme kinetics data of the KP are summarized in Table 1.
The kynurenine pathway.
Enzyme | Substrate | KM (mM) | Kcat (s−1) | Reference |
---|---|---|---|---|
IDO | 5‐Hydroxytriptamine | 0.02 | 0.043 | [5, 13, 15] |
Serotonin | 0.1 | 0.002 | ||
Tryptophan | 0.045 | 1.65 | ||
Oxygen | 0.042 | |||
TDO | Tryptophan | 0.222 | 1.4 | [16] |
Oxygen | 0.037 | |||
AFMID | N‐formylkynurenine | 0.05 | 100 | [17, 18] |
KAT I | l‐kynurenine | 4.7 | 3.35 | [19] |
KAT II | l‐kynurenine | 4.7 | 9.76 | [20] |
3‐hydroxykynurenine | 3.8 | 1.7 | ||
KAT III | l‐kynurenine | 1.5 | 2.3 | [21] |
KMO | l‐kynurenine | 0.89 | 1.88 | [22] |
Oxygen | 0.071 | |||
NADPH | 0.82 | |||
KYNU | l‐kynurenine | 0.495 | 0.23 | [23] |
3‐hydroxykynurenine | 0.028 | 3.5 | ||
3HAADO | 3‐hydroxyanthranilic acid | 0.016 | 64 | [24] |
Oxygen | 0.615 | |||
ACMSD | 2‐amino‐3‐carboxy muconate semialdehyde | 0.0065 | 1 | [25] |
QPRT | Quinolinic acid | 0.022 | 0.05 | [26] |
Enzyme kinetics parameters for the kynurenine pathway enzymes.
Although NAD+ is a final product of the KP, many of the intermediary metabolites, the so‐called kynurenines, have demonstrated to exert many effects on cellular homeostasis and bioenergetics resulting on changes in organism behavior or immune response. In brain, Trp is transported through the blood‐brain barrier by the large neutral amino acids transporter [27]. The imbalance on the levels of its metabolites (kynurenines) has been related with the progression of neurodegenerative disorders, such as Huntington, Alzheimer, and Parkinson due to their redox nature and their capacity to exert neuromodulatory mechanisms [28].
On a redox perspective, both 3‐HK and 3‐HAA represent a double‐edged sword. Reports show that 3‐HK is able to promote cell death due to the increase in reactive oxygen species (ROS) production; also, 3‐HK interaction with metallic ions promotes protein aggregation as well as cataract formation and toxicity in neuronal cultures without region selectivity [29–32] pointing this kynurenine as a pro‐oxidant and cytotoxic compound. In the same way, 3‐HAA is able to cause protein damage due to interaction with metals producing OH•; furthermore, this metabolite causes oxidative phosphorylation uncoupling and decreased oxygen consumption [31, 33]. On the other hand, there are reports pointing to the antioxidant and protective side of these molecules, demonstrating a 3‐HK‐induced decrease of oxidative stress parameters; also, it has been observed that 3‐HK acts as a free radical scavenger of radicals like O2•− [34, 35]; the antioxidant activity of 3‐HAA also has been reported showing free radical scavenging and ROS production decrease [36]. Finally, the protective effect of 3‐HK and 3‐HAA on the inhibited mitochondrial electron transport chain, as electron carriers, also has been reported [37].
On the other hand, Kyna is the only endogenous antagonist to N‐methyl‐d‐aspartate (NMDA) receptors known so far, it inhibits the α7‐nicotinic receptors, showing anticonvulsant effects on murine models as well as in human patients [38]. Recently, it was found that Kyna is a free radical scavenger of radicals, such as superoxide anion (O2•−), hydroxyl radical (OH•), and peroxynitrite (ONOO−), besides it is able to reduce oxidative damage caused by pro‐oxidants, so it is considered an endogenous antioxidant [39]. Furthermore, it has been shown that Kyna binds selectively to GPR35 receptor [40]; Kyna‐mediated activation of GPR35 leads to intracellular Ca2+ influx, inositol phosphate production and, attenuates LPS‐induced TNF‐α release and reduces acetic acid‐induced pain, suggesting that GPR35 could be mediating Kyna excitatory, anti‐inflammatory, and antinociceptive functions [40–42]. Contributing with the anti‐inflammatory response, Kyna also has been described as an agonist of the intracellular aryl hydrocarbon receptor (AHR); AHR translocation into the nucleus modulates the production of proinflammatory mediators and, as discussed below, inhibits T immune responses [43]. Because of Kyna is unable to cross the blood‐brain barrier, systemic l‐kyn administration has been used to show the protective effect of Kyna in 6‐hydroxidopamine‐induced Parkinson disease models, hippocampal β‐amyloid, and glutamate toxicity [44–46].
Contrasting with Kyna, Quin has been described as an agonist of NMDA receptors; in fact, it has been demonstrated that Quin is a pro‐convulsive agent which generates mitochondrial progressive dysfunction by reducing activity of respiratory complexes II and III [47], increases ROS production and lipid peroxidation in presence of Fe2+ [48], induces Ca2+ cellular influx increase, release of glutamate, and apoptosis [49–51]. Recently, the decrease in autophagy inhibition by Beclin‐1 reported in human astrocytes and neurons has been attributed to Quin toxicity [52]. Because of the selective damage that exerts in striatal spiny neurons with γ‐amino butyric acid and substance P, Quin has also been a good model to mimic early symptoms of Huntington\'s disease [53–55]. In addition, increases in Quin concentrations were observed in the cerebral cortex of macaques infected with retroviruses, particularly those with local inflammatory lesions [56]. Moreover, Quin levels are increased in cerebrospinal fluid in the acquired immunodeficiency syndrome and in HIV patients; also in humans, Quin levels are elevated after traumatic brain injury [57].
Moreover, kynurenine pathway has been related to inflammatory processes. It has been shown that IDO, KMO, and KYNU expression is strongly induced by proinflammatory cytokines, mainly interferon‐ɣ (IFN‐ɣ), interleukin 1 (IL1), interleukin 17 (IL17), or the tumor necrosis factor α (TNF‐α) during bacterial and viral infections in immune privileged tissues, such as brain [58, 59]. Thus, activation of the KP by proinflammatory molecules inhibits bacterial proliferation through tryptophan depletion, avoids autoimmune responses by limiting T cell activation and recruiting of immune regulatory cells [60–62]. The immunoregulatory role of the KP could act as a double‐edged sword, meanwhile it is inhibiting pathogen growth and regulating immune responses to avoid an autoimmune damage, the same activation during cancer supports tumor immune evasion and promotes tumor growth and invasiveness.
Beyond their role on neurodegenerative disorders, kynurenines have also been related with cancer progression in more than one way. It has been described that IDO expression is high in all thyroid carcinomas [63]. Moreover, l‐kyn and Quin promote neoplastic cell proliferation
All the cancer cells must possess a series of characters that allow them to develop tumors, these “hallmarks” let cancer cells to rapidly grow, evade cell death, migrate through the organism and colonize new tissues, modify their metabolic program, and to avoid immune destruction [69].
Before the establishment and development of a tumor, cancer cells must overcome elements of the immune system of the organism that can recognize, induce cellular signals, and finally, destroy exogenous agents or defective cells within the organism. In the early twentieth century, Paul Ehrlich formulated the idea that the immune system of an organism is able to recognize, destroy, and then protect against tumor cells. Later in the mid‐twentieth century, the “immunosurveillance” hypothesis was then postulated by Sir Macfarlane Burnet and Lewis Thomas, based on this original idea and in experimental evidence of that, mouse lacking of interferon‐γ responsiveness or with adaptive immunity defects, were susceptible to develop cancer [69, 70]. More recent evidence has demonstrated that the immune system not only protects against cancer progression, immune cells, and signaling but also promotes tumor cell establishment, and furthermore, cancer cells modulate immune mechanisms favoring tumor progression, transforming the idea of “immunosurveillance” into the “cancer immunoediting” hypothesis [69–70].
The cancer immunoediting hypothesis postulates that cancer cells and immune system create a set of dynamical interactions during the formation of a tumor; these interactions are arranged in three stages of the “cancer immunoediting,” or “The three E\'s hypothesis” process named: elimination, equilibrium, and escape [70]. During the elimination phase, cancer cells are recognized by the immune system and cytotoxic reactions induce cancer cell death; in the equilibrium phase, the cytotoxic mechanisms of the immune system act as selective pressure on tumor cells; cancer cells that survive, remain proliferating and establishing the tumor. Finally, at the escape phase, cancer cells are able to evade and suppress the immune mechanisms leading to the formation of tumors [70–72].
Cancer immunoediting mechanisms could be given by genetic alterations, proper of the cancer cells, which induce overexpression and secretion of suppressive molecules, such as the transforming growth factor‐β, the vascular endothelial growth factor, prostaglandin E2, and the soluble MHCI‐related gene A; cancer cells also recruit immune regulatory cells like T regulatory cells (Tregs), myeloid‐derived suppressor cells (MDSC), and tolerogenic dendritic cells (TDC); and finally, by induction of immune checkpoint, inhibitory molecules, such as PD‐L1 [73]. A second type of immunoediting is carried out by cytotoxic T cells of the own adaptive immune system, while exerting their protective role against cancer, T cells release cytokines like IFN‐γ which can also induce the production of immune suppressive molecules by tumor cells, during the equilibrium phase of the “cancer immunoediting” [73]. Remarkably, IFN‐γ is a strong inducer of IDO expression and activity which leads tryptophan metabolism through the KP in tumor microenvironment, and then to the triggering of the kynurenines’ immunosuppressive effects [73, 74]. In cultured human glioma, stimulation with IFN‐γ significantly increased the expression of IDO‐1, IDO‐2, kynureninase, and kynurenine hydroxylase, which potentiate the KP; whereas significantly decreased 2‐amino‐3‐carboxymuconate semialdehyde decarboxylase (ACMSD) and kynurenine aminotransferase‐I (KAT‐I), which reduce the neuroprotective metabolites [75].
As mentioned above, the own immune response against tumors could propitiate the formation of an immunosuppressive microenvironment, one of these mechanisms is carried out by IFN‐γ and other proinflammatory cytokines secreted by cytotoxic lymphocytes which strongly induce IDO expression. Beyond the increase of IDO levels in tumor cells, the formation and accumulation of different kynurenines have demonstrated immunosuppressive and immunoinhibitory effects [76].
Recent works have demonstrated that tryptophan starvation is able to inhibit T cell and macrophage cell viability and proliferation [77–80]. Furthermore, KP metabolites have also shown direct effects as immunosuppressive molecules. l‐kyn is able to activate the aryl hydrocarbon receptor (AHR) and thus to promote the generation of Tregs from naive T cells [81]. Moreover, there are reports showing that 3‐HAA, 3‐HK, and Quin promote Treg generation and that 3‐HAA and 3‐HK block T cell activation and induce cell death of CD4+ T and CD8+ T cells as well as of natural killer cells (NK) and B lymphocytes [82–86]. All these reports settle down the idea that immunosuppressive mechanisms carried out through the KP activation may be due to tryptophan deprivation of the tumor microenvironment or secondly, by the direct effect of the kynurenines on Treg recruitment and the impact on viability of effector T cells. Finally, both tryptophan depletion and the presence of the KP intermediates could enhance an immunosuppressive environment. It has been showed that l‐kyn, Pic, 3‐HK, 3‐HAA, and Quin reduced cell viability and induced apoptosis on CD4+ in absence of tryptophan [82, 83]; besides at lower concentrations were able to increase Treg‐mediated immunotolerance [84].
It is relevant to note that in some cases, the kynurenines are not produced by cancer cells but by other components of the tumor microenvironment, such as dendritic cells (DCs) or mesenchymal stem cells and also by microglial cells in the case of brain tumors [83, 87, 88]. Regarding dendritic cells expressing IDO, they can suppress effective immune responses through diverse strategies: by inhibiting the proliferation and effector functions of cytotoxic cells, such as NK and CD8+ T lymphocytes, as well as plasma cells; by inducing of CD4+ CD25+ FOXP3+ regulatory T cells from naive CD4+ cells; and by triggering immunosuppressive activity in adjacent IDO‐expressing DCs [89]. Possible implication of IDO2 in cancer immunosuppression has been suggested due to reports showing its ability to mobilize the nuclear factor interleukin 6 inhibitor, LIP [6].
Thus, locating the IDO expression and the kynurenines in the “Three E\'s” context, it would be in this way: IFNɣ, TNFɑ, and proinflammatory cytokines secreted by cytotoxic lymphocytes, while killing recognized tumor cells during Elimination and Equilibrium phases, induce IDO expression of tumor cells, those that survived to immune response, and of other infiltrating cells, such as DCs and macrophages. Tumor cells expressing IDO, deplete tryptophan from the tumor microenvironment and begin to produce kynurenines and NAD+; tryptophan depletion from, and release of kynurenines to the tumor microenvironment, inhibit T cells and NK proliferation; induce apoptosis, while promote differentiation and proliferation of Tregs, and recruiting of DCs and macrophages. NAD+ production allows cancer cells to overcome DNA damage and oxidative stresses, promoving their proliferation during the Escape phase.
Because of the importance of the KP in brain and the relationship of tryptophan catabolism with immune modulation during cancer, researchers have begun to clarify the role of the activation of this pathway on glioblastoma progression for further development of new strategies to treat this illness.
Astrocytes are non‐excitable nervous cells of great importance for the physiological maintenance that exert on neurons, by regulating ions and excitatory amino‐acids concentrations on synaptic regions, forming the brain‐blood‐barrier (BBB)‐mediating neuron‐blood stream signaling and regulating the transport of nutrients into and out of the brain [90, 91]. Beyond this, astrocytes can be differentiated on a wide span of morphological, physiological, and genomic subtypes [90–91].
Deregulation of cell proliferation and uncontrolled proliferation caused by mutations of certain genes lead astrocytes to transform into astrocytomas. Astrocytomas have been classified into four subtypes depending on the rate of proliferation and the grade of malignancy: grade I pilocytic astrocytomas are non‐invasive tumors, they represent the less malignant of astrocytomas; diffuse astrocytomas are grade II tumors that tend to invade peripheral tissues but their growth rate is slow; anaplastic astrocytomas grow faster than diffuse astrocytomas and tend to form tentacle‐like projections into surrounding tissues, instead of grade III anaplastic astrocytomas, their frequency is low; finally, glioblastomas (GBM), also known as glioblastoma multiforme, are grade IV tumors, these are the most malignant of astrocytomas [92]. GBM can be originated
Incidence rate of GBM is 3.19 per 100,000 people with a median age at diagnosis of 64 years old for primary GBM, and 45 years old for secondary GBM, the median survival overall for diagnosed and treated GBM ranges between 12 and 14 months [94, 95]. Furthermore, GBM represent 2.8% of brain tumors during childhood [96]; however, its frequency is lower in adults, high‐grade astrocytic tumor incidence rate is 0.85 per 100,000 people being more frequent in children between 5 and 9 years old, also, the median survival overall is over 43 months [97–99]. The most common treatment for GBM is surgical resection of the tumor, followed by temozolomide‐based chemotherapy, and 5000–6000 Gy radiotherapy which prolongs the lifespan 202 weeks [100–102]. Despite the treatment, the survival of afflicted patients is no longer than 14 months and only 5% of the patients have a survival rate of 5 years. It is believed that the lack of response of GBM to the multimodal treatment is due to multiple factors that combined, make GBM resistance and aggressiveness.
A major character among GBM is a loss‐of‐function mutation of Retinoblastoma (Rb) gene, a cell cycle regulator protein at the phase G to phase S checkpoint, that also regulates apoptosis and differentiation, which occurs on 77% of GBM [103, 104]. Instead of that, another genetic mutations and genomic expression patterns differ among GBM, integrated genomic analysis originated four types of GBM named: proneural, associated with PDGFRA, IDH1, and TP53 mutations; neural, expressing neuronal markers, such as NEFL, GABRA1, SYT1, and SLC12A5; classical, showing amplifications on EGFR expression and deletions of Ink4a/ARF locus; and mesenchymal, characterized by overexpression of CHI3L1 and MET so as deletion of NF1 [103]. Several other mutations in key oncogenic signaling pathways, such as the receptor tyrosine kinase (RTK)/RAS/PI3K, p53 pathways, lead to uncontrolled tumor cell proliferation, genomic instability, and resistance to therapeutic strategies.
GBM may have a wide cellular diversity, more than tumor cells which are polygonal or spindled small sized with big nuclei, GBM‐initiating cells (also called glioma stem cells) are responsible for cell proliferation and renewal of GBM cells, also confer chemo‐ and radioresistance; infiltrating multinucleated cells, such as lymphocytes, macrophages, and neutrophils, and cells with lipid vacuoles are present in these tumors [105]. Because GBM are highly angiogenic tumors, blood vessels surrounded by pericytes are also present in tumors. GBM also show necrotic regions among the central body tumor and some other necrotic foci in outer regions of the tumor [105, 106]. In addition to all these mechanisms, the GBM has the ability to create an immunosuppressive environment that prevents the response lead by the immune system against GBM.
Historically, the brain has been considered an immune privileged organ due to the inability of reject exo‐grafts and the lack of response in case of infection [107], as well as, absence of a normal response of the lymphatic system and the extremely distinctiveness of antigen‐presenting cells (APCs) in brain tissue [108, 109]. However, diverse studies have recently found that there is not an absolute isolation of the rest of the organism; moreover, within the dural sinuses is located a lymphatic system that connect with the deep cervical lymph nodes, able of taking immune cells and macromolecules into the CNS [108].
Even with this lymphatic system, the access to CNS is highly regulated, mostly by the BBB [110]. The BBB is a highly selective layer composed of basement membranes, brain pericytes, astrocytes, and neurons, which have the ability to reject more than the 90% of small molecules, allowing the entrance just to certain lipophilic molecules [111]. However, it has been observed that when a GBM appears, this tumor easily disrupts the BBB due to this abnormal structure, which has as consequence the free‐crossing of a more varied group of substances into the CNS [111] and also cells of the immune system.
GBM is infiltrated by several cell types, such as monocyte‐derived cells, microglia, and activated T cells. These immune cells are recruited by chemotaxis to the tumor and together with molecules secreted by GBM itself, such as IL‐10, prostaglandins, and TGF‐β1 (Table 2), playing a major role in the immunosuppression of the tumor [112–113]. Specifically, several studies have found that the infiltration of T cells subtypes is higher in GBM than any other CNS tumor [114], comprising between 10 and 30% of cells within the tumor mass [115–116]. Due to the production of immunosuppressive cytokines, inhibition of T cell proliferation, activation of Tregs and hypoxia, an immunosuppressive environment, is made in GBM, which can be enhanced by the activation of the KP.
Molecule | Effect | Mechanism |
---|---|---|
Interleukin‐10 (IL‐10) | Induce apoptosis in T cells, possibly through the expression of Fas‐ligand | [121–123] |
Tumor‐promoting cytokines | Dampen the antitumor immune response | [124, 125] |
Interleukin‐6 (IL‐6) | Shifting adaptive immunity to humoral response (TH2) | [124, 126] |
Prostaglandin E2 (PGE2) | Dampen the antitumor immune response suppressing lymphocyte proliferation | [124, 125, 127–129] |
TGF‐β1 | Ability to polarize TAMs toward M2 phenotype | |
CD70 and ganglioside | Promotion of T cells apoptosis | [130, 131] |
Colony stimulating factor‐1 (CSF‐1) | Stimulating of monocytic cells | [124, 126] |
Ability to polarize TAMs toward M2 phenotype | ||
Basic fibroblast growth factor (BFGF), | Dampen the antitumor immune response | [124, 125] |
Vascular endothelial growth factor (VEGF) | Proangiogenic factor. | [132] |
Support of vascularity and tumor growth | ||
Factor‐1α (HIF‐1α) | Activation of Tregs and production of vascular endothelial growth factor (VEGF) | [133] |
Transcription 3 (STAT3) | Synthesis of hypoxia‐inducible factor‐1α (HIF‐1α) that subsequently induces activation of Tregs and production of vascular endothelial growth factor (VEGF). | [133] |
Promotion of angiogenesis |
Molecules implicated in the immunosuppression of GBM.
Because of the high immunosuppressive conditions in the GBM, new therapies have begun to being developed, focusing on antitumoral immune response for improvement of GBM patients. Thus, epidermal growth factor receptor (EGFR) variant III‐specific peptide vaccination and autologous tumor lysate‐DC vaccination have been tested with successful results on phase I and phase II clinical trials [117–120]. However, a better understanding of the immunosuppressive mechanisms occurring during GBM development, including those carried out by IDO activity and the kynurenines, could impulse the furtherance of new tools and strategies for GBM treatment.
Kynurenine pathway enzymes are overexpressed in GBM. Upregulated expression of these enzymes has been related to severity of gliomas and patient survival. The IDO expression in 343 glioma specimens and correlated to patient survival has been analyzed [134], this expression was associated with poor prognosis and was more frequently observed in high‐grade glioma. Moreover, in an orthotopic GL261 cell tumor model was shown that IDO‐competent brain tumors increased the recruitment of immunosuppressive Tregs, and decreased the frequency of CD8+ T cells compared with IDO‐deficient brain tumors [134]. Another study, including 75 gliomas, showed higher expression of IDO in malignant gliomas compared with low‐grade gliomas. Moreover, stronger IDO expression was associated with shortened survival time in GBM patients [135]. Additionally, it has been reported that glioma cells have increased mRNA expression of IDO1 and IDO2 compared with human fetal astrocytes and human adult astrocytes cultures as well as decreased Kats mRNA expression, and these expression enhanced when cells were stimulated with IFNɣ [75]; the same work also reported increased Kyn/Trp ratios and decreased Kyna/Kyn ratios in the plasma of glioblastoma patients compared with healthy people [75]. The levels of Trp and Kyn were evaluated in GBM patients before and after tumor resection. Interestingly, both Trp and Kyn significantly decreased after 48 h and 10 weeks after surgery. In addition, patients with a high‐ratio Kyn/Trp had worse mean overall survival compared with patients with lower ratio [136].
The significantly increased expression of IDO in cancer cells and in the tumor microenvironment has arisen as a promising target for GBM treatment, based on the inhibition of IDO as a potential therapy for cancer patients. Among the first strategies, is the systemic administration of 1‐methyl tryptophan (1‐MT), a competitive inhibitor of the IDO, which delayed tumor development in a murine model of Lewis lung carcinoma [137]. Subsequently, it was described that the expression of IDO in immunogenic cells (P815B) avoided their rejection by preimmunized mice, an effect that was associated with the inhibition of specific T cell response [138]. This effect was partially reversed when preimmunized mice were administered with 1‐MT [138]. Due to the results observed in animal models, 1‐MT has been tested and approved on phase I clinical trials in patients with solid and solid metastatic neoplasms, lung, ovarian, Fallopian tube, and breast cancer showing disease stabilization in most cases [89, 139–141].
Concerning to GBM, at least three clinical trials involving IDO inhibitors are in recruiting status (Feb. 2017), but the use of 1‐MT on
Despite reports pointing that 1‐MT has a greater affinity for IDO2 than for IDO [6, 7], it is of mention that the majority of reports about the targeting of the KP for cancer treatment are focused on IDO inhibition. But IDO is just one of the enzymes that fuel this catabolic route, so the better understanding of the roles of both IDO2 and TDO in cancer development and immunosuppression would result in better ways for combating cancer [144].
As mentioned above, in most cases, IDO expression as well as kynurenines production and immunosuppressive mechanisms are carried out by infiltrating tumor cells. For GBM, microglial cells are an important source of kynurenines so, the microglial depletion could be another important strategy for tumor mitigation. Studies focusing in microglial depletion through the use of CSF‐1 receptor inhibitors have shown prolonged mice survival and enhanced antitumoral immune response when animals were treated in combination with DC vaccination [145, 146]. The effect of microglial elimination on IDO expression and on the levels of KP metabolites, still remains to be elucidated, but the immune response reported with the use of the CSF‐1 receptor inhibitors settle down some clues about what could happen in the KP context.
Thus, the use of IDO inhibitors and microglial elimination in combination with classical chemotherapy and radiotherapy in GBM murine models, as well as the clinical trials that have tested 1‐MT in different kinds of solid and metastatic tumors has shown promising results for targeting IDO and the KP against GBM.
GBM is an astrocyte‐derived tumor, the most common of brain tumors, characterized by its high proliferation rates, genomic instability, and invasiveness, as well as to being a high immunosuppressive tumor. The nature of GBM results in a rapid expansion into the surrounding tissues, associated with poor prognosis and patient low survival despite classical treatment of these tumors, tumor extirpation, temozolomide therapy, and radiotherapy, which only prolongs median survival over 2 months.
In this chapter, we have discussed the importance of the tryptophan catabolism through the KP during GBM development. Activation of this catabolic route provides cancer cells a constant supply of NAD+ and promotes the expression of damaged DNA repairing enzymes, which allow cancer cells to have an active metabolism, and to bypass redox stress and DNA damage pressure (Figure 3).
Global scheme of the role of IDO expression and the kynurenine pathway on glioblastoma development. During glioblastoma formation, a population of tumor cells is recognized and eliminated by the host immune system (cytotoxic T lymphocytes, helper T lymphocytes, and natural killer cells). While eliminating the recognized tumor cells, cytotoxic T lymphocytes secrete IF Ny, TNFα, and other proinflammatory cytokines which strongly induce IDO expression and the kynurenine pathway activation in survivor glioblastoma cells and tumor infiltrating cells (dendritic cells and tumor‐associated macrophages). Glioblastoma IDO expressing cells maintain a rich NAD+/NADH pool which provides redox balance, energy supply, and active DNA repairing mechanisms, facilitating genomic instability and tumor growth; also in glioblastoma cells,
Furthermore, IDO expression and elevated Kyn/Trp ratios are related with poor prognosis and low survival of GBM patients. The expression of key enzymes of the KP is induced by stimulation of cytokines secreted during antitumoral immune responses, after this, tryptophan depletion and kynurenines production inhibit effector CD4+ and CD8+ T cell and NK cell proliferation, meanwhile promote Treg differentiation and MDSC infiltration into the tumor, attenuating antitumor responses. It is of note that IDO expression and immunosuppressive mechanisms are not carried out by cancer cells alone, but tumor infiltrating cells are also able to synthesize IDO and to promote an immunosuppressive environment (Figure 3).
The results of the use of IDO inhibitors, like 1‐MT, in
This work was supported by CONACYT Grant 262010.
Worldwide, the mining sector is classified as the most dangerous work and customarily ranks within the top 3 occupations for related diseases and fatal accidents [1, 2, 3, 4, 5, 6, 7]. The complete health of the miners includes physical, social, and psychological, including protection from injury or any occupational disease [8]. Whereas safety is associated with the physical mining environment and interventions done to reduce exposure to risk [8]. Within the context of this review, the authors are concerned that if mining remains unsafe as occupational health practitioners how can we improve and make sure a healthy and safe workplace? Smith et al. highlighted the necessity for mining corporations to accommodate international and national safety and health laws and laws, but there’s a requirement to implement preventative strategies to accommodates those standards and laws [1]. In Africa, though several African states have comprehensive laws regarding activity health and safety standards and hours of labor, systems to make sure compliance, their observance is usually weak and under-resourced in several organizations [9, 10]. According to the African Union’s Mining Vision and Bocoum, a lot stays to be done to carry mining practices. Policies, regulatory capacity, and services associated with mine health need to be massively progressed, and standardized carrier shipping models want to be set up each nationally and domestically [10, 11].
The SA mine health and safety council have introduced pointers for compliance with the Mine Health and Safety Act (29 of 1996) [12]. However, the high rate of sub-standard performance has shown that accessible rules and policies have not led to the anticipated result [13]. Governmental and trade executives, policymakers, and material scientists voiced issues and conducted various reports stating matters and the risks of an offer crisis. Positively safety rules are necessary to form a healthy and safe work atmosphere, but it’s of significant importance to explore the social relations within the employment context (organization), the individual factors (beliefs, attitudes, and behavior), and also the cultural processes that contribute to non-compliance with health and safety standards within the mining trade [14]. Given these gaps, there is an obligation to identify the ways that may enhance compliance with health and safety standards. Muchiri emphasized the necessity and the duty for the occupational health and safety professionals, employers, workers, agencies, and alternative stakeholders to incessantly develop and implement multi-faceted OSH ways [9]. Within the context of this review, compliance shall refer to the proper practice of the staff and also the organization following the health and safety standards within the mining industry [14].
This review aims to analyze the present state of compliance with the health and safety regulations/standards, among the South African Mining industry and to highlight the importance of the implementation of preventative strategies through the occupational health clinic. The review additionally provides insights upon that a part of health and safety legislation standards would like an improvement. in addition, this review intends to create clear links between the studies and also the activity health and safety legislation and also the conclusions, confirm any controversies, weaknesses, and gaps with the compliance in the mining industry and generate information and data on the world strategies that may be used for compliance and making property health and safety atmosphere within the mining industry. This review adds worth to existing electronic databases through the integration of analysis results.
The review adopted the systematic review technique that enabled the reviewers to discover and investigate the systematic evidence of both qualitative and quantitative research, government and private documentation, and also the laws bearing on occupational health and safety compliance. The subsequent systematic steps as outlined by Cronin, et al.; Ramdhani et al. were applied to cut back literature-review errors and bias and to supply a clear, structured, and comprehensive summary of the obtainable literature (Figure 1) [15, 16].
Systematic review steps adopted from: (Ramdhani et al., Hempel, Xenakis & Danz).
Step 1: Defining the research question.
As per Hempel, Xenakis, and Danz it’s important to layout the requests to be addressed in occupational safety and health systematic review to recognize the point and extent of the survey [17]. Additionally forming the inquiries can coordinate the reader on the sort of information looked still up in the review. The examination question was illustrated through the conversation with the supervisor and co-supervisor, meeting with the master’s word related wellbeing specialists to affirm that the audit has significance to genuine difficulties. The examination question was: What is the current situation with compliance with the health and safety guidelines /principles among the SA mining exchange and what are the procedures, which will be created to affirm the compliance with the health and safety enactment/norms among the SA mining industry?
Step 2: Setting for inclusion and exclusion criteria.
Shamseer, Moher Clarke, et al. laid out that setting for incorporation and prohibition measures guarantees that the survey is led in a coordinated manner [18]. Also, it accommodates the straightforwardness of how the qualities and restrictions were surveyed. Furthermore, the conceptual model in the current study guided the researcher through the review to explore the defined study question. The PICO (population, intervention, comparison, and outcome) format was followed [19]. The conceptual model defined the population which was the mine occupational health practitioners, satety representatives, occupational health clinics, miners, the mining organizational and the mine management, interventions, in this case, was the legislation, standards, and the preventative strategies that guide the employees to comply with the health and safety.
Step 3: Conducting a literature search.
The online database literature search enclosed a mixture of South African and international government OHS legislation, policies, standards, reports from the labor departments and international labor workplace, the qualitative, quantitative, and mixed- methods scientific journal articles, conference proceedings. Seven databases are enclosed PUBMED, EBSCOHOST, SEMATIC SCHOLAR, GOOGLE SCHOLAR, domain EDU, SAFE WORK AUSTRALIA. gray literature including conference proceedings, dissertations, theses, government information, and committee reports was retrieved from searches in web OF SCIENCE, ILO, WHO. HSELINE, NIOSHTIC, and from OSH UPDATE.
The search strategy adopted Boolean operators combined sets of keywords, using AND/OR terms for the selection of articles and reports [20]. The terms from the subsequent 7 categories were accustomed to search the articles and gray literature (Prevention, Compliance, health and safety, Occupational health practitioner, standards, legislation, and mining) (Table 1).
Occupational health and safety- related search terms | Mining health, medical surveillance, mining safety, occupational health, safety behavior, safety culture |
---|---|
Health and safety compliance search terms | Adherence, legislations, guidelines, standards, policy, preventative strategies |
Occupational health search terms | Occupational health practitioners, health and safety representatives, occupational diseases, occupational injury, and accidents, safety culture |
Mining health strategies related search terms | Prevention levels, occupational health interventions, |
Search terms.
Step 3: Assessing the quality of literature included in the review.
This review enclosed all the articles, reports obtained when databases were integrated, duplicate articles were removed, and extra articles provided by content specialists had been identified. Secondary sources, including textbooks and review articles or descriptions or outlines by someone aside from the first investigator, were removed [20].
Only studies that were revealed between 1994 to July 2021 within the English peer- reviewed journal, report, or websites were reviewed to identify gaps within the compliance with the health and safety within the mining industry. Moreover, abstracts solely were not enclosed. The studies enclosed were those that explored the compliance and the preventative strategies for health and safety within the mining industry. in addition, the studies, that reported on the present state of compliance with the health and safety legislation and standards, the role of occupational health clinics and practitioners in promoting health and safety within the mining industry, and also the occupational interventions/strategies to reinforce the compliance.
Step 4: Analyze, synthesize and disseminate the findings.
The studies which have been protected were clustered and prepared by using ideas, which emerged as themes. To offer enough substance to a topic, standards from at the least 3 articles had been required. Five thematic domains emerged from the literature. Six thematic domains emerged from the literature: Global laws, legislation, and standards on health and safety compliance within the mining industry; African countries mining health and safety compliance literature; health and safety compliance literature within the South African mining industry; Legislations; preventative strategies to improve the health and safety compliance within the mining industry and occupational health practitioners role in improving health and safety standards compliance.
Step 4: Analyze, synthesize and disseminate the findings.
The analysis and synthesis process is shown below Figure 2.
A flow diagram (literature).
Health and Safety compliance is the volume to which personnel adheres to health and safety standards, techniques, jail responsibilities, and wishes. It’s furthermore accomplice diploma absence of injuries and incidents within the geographic component [21]. The majority of mine fitness and safety government international agree that the fundamental causes of mine accidents and fatalities are dangerous conditions, terrible control, and mainly non-compliance with the health and protection standards [22]. Furthermore, Vassem, Fortunato, Bastos, and Balassiano documented that the excessive incidence charge of accidents inside the mining enterprise calls for the information of interpersonal family members within the employment context (corporation), the individual factors (beliefs, attitudes, and behavior) that contribute to non-compliance with health and safety standards within the mining industry [23]. On the opposite hand the venture with the implementation of occupational legislation and requirements is that miners understanding of occupational regulation is confined and adherence is as a result impaired [24]. Therefore, to make certain compliance with fitness and safety requirements occupational fitness occupational health practioners have a duty to increase cognizance of health risks that impact the people’ health and safety, as well as the measures which can mitigate the dangers [25].
The SA mining industry is under the spotlight with an increase in accidents and fatalities. In 2019 SA reported a total of 2406 injuries and 51 deaths in the mining industry [26]. This are a serious concern considering that In 2016, the chamber of mines signed a declaration of actions pledge as a change to improve the mining industry occupational health and safety to zero harm by 2024, aiming to generate a culture change in an industry that will transform the behavior of people at all levels [27].
Occupational health and safety standards plays important role in guiding all the miners on health and safety-related issues focusing more on prevention. However though there are available standards, the occurrence of injuries and occupational diseases remains to be a challenge worldwide. The literature revealed that globally in every 15 seconds a miner dies [28, 29]. World Health Organization (WHO)outlined occupational health and safety as ‘the advancement and maintenance of the most significant level of physical, mental and social health of miners in all occupations by preventing health risks and controlling danger and the adaption of work to miners and their positions [30]. Furthermore, it is of utmost importance to note that a safe and healthy working environment influences the quality of life at the individual level to substantial impacts on public health at the societal level [30].
Globally, the health and safety of the miners have raised serious concerns. In the United States (US) the former chief executive director of the upper big branch coal mine was sentenced to a year in prison for the death of 38 miners who were killed after a coal explosion [31]. He was convicted for a workplace safety violation by putting profits of the company ahead of the safety of miners and creating a culture of non-compliance within the organization [31]. Dragan, Georges, and Mustafa’s study in Canada indicated that cultural factors within the organization especially from the management focusing on performance and efficiency and neglecting safety plays a key role in creating conditions for triggering major accidents [32]. More particularly from the administration with more emphasis on the execution and productivity and dismissing the safety and wellbeing of miners.
Different countries have laws and regulations in place at the workplace aiming to protect the health and safety of individuals in their occupations. Occupational health and safety laws across nations share many similarities highlighting that the health and safety of employees must be secured through the assessment, analysis, adjustment and reducing the risks and hazards for illness and injury at the workplace [33, 34]. Occupational health and safety compliance shapes the required or desirable behavior in the workplace. Furthermore, compliance is linked to the safety culture or climate in the organization, which is believed to shape employee behavior through expectations [35].
Statute law may uphold extra obligations, start explicit obligations, and structure government bodies with the power to direct work environment wellbeing and medical problems. As set by Spada and Burgherr; Mabika, reinforcing the wellbeing controller is required, upheld by the authoritative approaches [36, 37]. Such drives can save the existence of mine accidents and occupational diseases in both developed and undeveloped countries [37]. United Kingdom (UK) is one of the created nations with a fruitful record of wellbeing and safety practices in the mine. As indicated by Uyanusta Kucuk and Ilgaz, wellbeing and safety laws in the UK have been in existence for more than 200 years [38]. Moreover, the laws came because of political reactions to social issues emerging from the unsettling influences of the industrial revolution [38]. Among other enactments, the mines and safety act 1954 was the broadest safety enactment in the UK. The demonstration set down legal obligations on mine chiefs and offered.
A triangulation study led by Kheni and Braimah; Mustapha, Aigbavboa, and Thwala conducted in Ghana looking at the institutional and lawful conditions identifying with health and safety management referred to helpless coordination of activities related to health and safety standards, absence and unwanted degree of consistency with significant H&S enactment as the serious issues [39, 40].
The greater part of the African nations is known for deprived safety and health practices [41, 42]. Takala and Saarela featured that low-pay nations in Africa and Asia have recorded raised paces of injuries and fatalities contrasted with created nations, for example, Europe and America [43]. Besides, it has been assessed that 54000 fatality related to occupational accidents happen in Sub-saharan Africa yearly contrasted with 16000 fatalities in Europe and America. Boniface, Maseru, Munthali and Lett study results on Occupational injuries and fatalities in Tanzania highlighted the requirement for improving health and safety principles systems in the mines [44].
The South African mining industry does not have a good reputation for health and safety due to recurrent accidents and fatalities. One of the largest mining companies in SA with a major interest in both platinum and gold mining (Sibanye) outlined that one of the causes of fatalities was non-compliance by miners and management as people try to take shortcuts [45]. On the contrary, the union representatives within the mining industry blame the high pressure to reach production targets means that miners remain in unsafe working conditions and environment [39].
The South African mining Act, 1996 (Act 29 of 1996) was endorsed to improve health and safety performance and great emphasis was placed on adherence to mine standards [46]. Furthermore, different types of legislation were passed to assist in the transformation6and “improvement of the safety standards in the mining sector, among others, the Skills Development Act of 1998 (SDA), Broad-Based Black Economic Empowerment Act, 2013 (BBEEA), (Minerals Petroleum Resources and Development Amendment Bill 2013 (MPRDAB), Compensation for Occupational Injuries and Diseases Act, 1997 (COIDA), Occupational Diseases in Mines and Works Amendment Act, 2002 (ODMWAA), Labour Relations Act, 1996 (LRA), Basic Conditions of Employment Act of 1997, Mining Charter 2010, and the Constitution of the Republic of South Africa, 1996”.
The Society for Mining, Metallurgy and Exploration (SME) Mining Engineering Handbook, expresses that all mining tasks are needed to adhere to local, provincial, and governmental guidelines that indicate mine health and safety guidelines and norms, environmental protection, and work relations. The nature, degree, and toughness of these guidelines, at last, administer the mining activity [45].
Lack of emphasis on the promotion of health of mine-workers made the Commission to endorsed to improve the state of the safety standards in the mining sector, among others, the enactment of a new Mine Health and Safety Act 29 of 1996 (hereinafter referred to as MHSA), which started operating from January 1997.140 The Act (MHSA) has established a council known as Mine Health and Safety Council (MHSC), that contemplates the status of health and safety in the mining sector, recommends policy and legislation, commissions’ research, and offers suitable advice to the Minister of Mineral Resources.
The Department of mineral resources and energy South Africa is responsible to promote and regulate the minerals and mining sector in SA. Furthermore, the Department also has the responsibility to ensure that all the mining companies in SA follow and comply with the health and safety legislation. They also have an obligatory role to take action when the mining companies do not implement and comply with the regulations. Laws and standards. The mineral resource department can close/terminate the mining activities or take the mining companies to the Court of Justice if they fail to comply. The following regulations guide all the mines in SA on health and safety.
The MHSA regulates the mining sector focusing on the health requirements in the mining industry.
The goals of this act are to accommodate the wellbeing of the workers and different people at mines: support consistent with the standards of health and safety; take into account the execution of health and safety measures; accommodate suitable frameworks of the employee, employer, and state participation in health and safety matters; build up delegate three-sided organizations to audit enactment, advance wellbeing and upgrade appropriately designated research; accommodate compelling observing frameworks and assessments, to guarantee that there are examinations and requests to further develop health and safety; advance preparing and HR improvement; manage businesses’ and workers’ obligations to recognize hazards and prevent, control and limit the danger to health and safety; settle in the option to decline to work in hazardous conditions, and to offer impact to the public worldwide law commitments of the Republic identifying with mining health and safety [12].
Section 13 of MHSA outlines the legal requirement for all the mining organizations in SA to have an OMP either on a full-time or part-time basis. The OMP has legal duties and ethical duties when ensuring the overall health of the miners [12, 28, 46]. They play a major role in preventative medicine, determining the fitness and ensuring that every person in the mine (both the employer and the miners undergo medical surveillance. Medical surveillance is a scheduled program that includes medical examinations, conducting different tests depending on the job that the miner applied for such tests includes audiometry, spirometry, and vision screening. The purpose of medical surveillance is to ensure that all the miners are fit to perform their duties without endangering their health and safety. Medical problems that may arise due to workplace exposure are also identified [12, 28]. The occupational medical practitioner must ensure that the medical surveillance must be suitable and be planned in such a way that it affords the miners to gain knowledge that can be used to the information that employees can use to eradicate, govern and reduce risks and hazards related to health and safety [28, 46]. This is achieved through continuous health education providing information to the miners relaxed to their medical results e.g. education related to audiometric test results on hearing loss. Medical surveillance includes the following types of medical examinations:
Pre-placement/baseline medical examination
It is a legal requirement for all mining organizations to conduct a pre-placement examination to be done before the miner can be appointed and placed in a job. The examination assists in the assessment of the miner’s suitability for the position applied and also the work environment that will be exposed to. More importantly pre-employment is also done to ensure the safety of the miners and others ensuring that the new employee does not pose risk [28].
Periodic medical examination
This examination is done every year or six months depending on the risk that the miner is exposed to. The examination I also done if the exposure risk increase or there is deterioration noted in the test results, when the miner is transferred from one department to another, after being involved in a serious injury or sickness [28].
Exit medical examination
This examination is performed before the miners leave their current employment. It s a legal requirement for the miners to produce their exit fitness certificate to their new employer. The exit medical examination safeguards the organization against future medical claims. The records are kept for 40 years [28].
The target of the demonstration is to accommodate the wellbeing and safety of miners at work, particularly regarding the utilization of apparatus (South Africa, 1993). Moreover, the Act accommodates the safety of miners against dangers to wellbeing and safety emerging from or regarding the exercises of people at work. This act recognized settled an advisory council on occupational and safety [47]. The overall obligations of the business and the miners in the work environment are likewise specified [47].
All the mines must appoint a health and safety team including health and safety representatives where there are 20 or more employees. Whereas if the mine has 100 or more miners the health and safety committee should be established. The health and safety representatives have the following major roles to play in ensuring the safety of the miners:
Review health and safety measures whether they are effective or not
Identifying possible hazards and the occurrence of incidents
They represent all the miners concerning health and safety and investigates all the complaints related to the safety of miners.
They do workplace inspections to identify potential health and safety risks
They participate in the inspection of the mine by the inspectors and provide safety- related information when needed.
They form part of the health and safety committee and participate in the internal health and safety audit.
According to the Mine Health and Act (29 of 1996), all organizations must employ a practitioner who is in the position of qualification in occupational medicine recognized by the Interim National Medical and Dental Council of South Africa or the South African Interim Nursing Council [12]. The occupational health practitioners are the largest single group of the multidisciplinary health care team at the workplace. Therefore, OHN is the frontline in protecting and promoting the health of the working population.
The occupational health practitioner is gifted in injury or diseases preventative skills and interventions. The OHP might recognize the requirement for, survey, and plan mediations to, alter working conditions, frameworks of work, or change working practices to decrease the danger of exposure to hazards [48]. Moreover, OHP experts are skilled in thinking about factors, like human conduct and habits about real working practices. They additionally team up in the origination, and rectification of work factors, decision, and quality of protective equipment, protection of miners from injury and illnesses, just as giving guidance in issues concerning the assurance of the climate [28, 48]. The OHP close relationship with the workers, and involvement with the management, they are in a decent situation to distinguish early changes in unsafe working practices, recognize miners challenges over health and safety, and present these to management in an independent objective manner can be the catalyst for changes in the workplace that lead to primary prevention by present these to the executives in a free target way can be the motivation for changes in the work environment that lead to essential counteraction [48].
The occupational health professionals inform on a wide reach concerning medical problems, and especially on their relationship to working capacity, wellbeing, and safety at work or where alterations to the work or workspace can be made to assess the changing wellbeing status of representatives [28]. In many regards, organizations are not exclusively worried about just those conditions that are straightforwardly brought about by work however, they need occupational health professionals to assist with attending to any wellbeing related issues that might emerge that may impact the miner’s participation or execution at work, and numerous representatives like this degree of help being given to them at the work environment since it is so advantageous for them [43]. Specifically, the improvement of medical care administrations for miners at the workplace. With regards to this survey, the OHP plays a significant part in guaranteeing the health and safety of the miners through primary, secondary, and tertiary avoidance [49].
Different scholars have acknowledged that there is a gap in the literature on the management of compliance with the health and safety strategy. Moreover, scholars have also raised a concern that the impact of legal non-compliance is even more scarce in the literature [49, 50]. Previous research done by Tibane and Niemand on challenges experienced by employees relating to safety compliance emphasized the importance of the development of strategies to reduce safety threats caused by poor compliance as a result of unsafe acts [51]. The question is that if they are safety regulations available and miners are aware of the dangers, what is the rationale behind poor compliance with the health and safety standards [52, 53].
The strategies are aimed at can be named preventive and treatment mediations. Precaution mediations are typically presented to every one of the excavators helping them to take on well- being conduct and sound way of life unconstrained and without incidental effects fuming them to search for help. On the other hand, Bagherpour et al. argue that preventive strategies need to be applied before the incidents, but preparative adjustments must be implemented both before and after the occurrence [6]. Preventive interventions, accordingly, are named as a primary, secondary, or tertiary counteraction.
Preventative strategies are normally offered to all the miners assisting them to adopt a safe behavior and healthy lifestyle spontaneous and without side effects seething them to look for help. More importantly, the literature revealed that compliance with health and safety law involves the development and implementation of an effective health and safety preventative system and building a positive health and safety culture at work [54]. Preventive mediations, thusly, are named as primary, secondary, or tertiary prevention [55].
In occupational health primary, preventative strategies are aimed at eradicating risks and exposures at the workplace before they occur. This level of prevention is important because the effect has not yet occurred yet the extent of the risk is visible [56]. In the occupational health clinic, primary prevention focuses on health promotion and protection within the context of a safe and healthy work environment [21]. This is achieved through continuous health education, conducting medical surveillance, and monitoring of chronic diseases thereby enhancing employees’ morale and maintaining optimal health. However, in the mining sector, the following health promotion programs are essential to promote good health and to prevent occurrences of accidents and diseases, this may include such elements as continuous health education on health and safety-related topics such as noise-induced hearing loss, chronic disease monitoring, and management, accident prevention, the importance of personal protective equipment’s, medical surveillance to identify and prevent the occurrences of health- related illnesses that might be caused by the work environment. Part of primary prevention is the assessment of health risks, this is achieved through continuous inspection by the occupational health practitioners and the safety team to identify and observe the work environment and working practices that might put the miner’s health at risk [21, 47]. More importantly, the health promotion activities have the potential to change the miner’s health practices such as choice of a healthy diet, exercising more frequently to prevent occurrences of chronic diseases. Additionally, the primary prevention activities have the potential to reduce the incidence of injuries and accidents because miners will be having more knowledge on health-related risks that might endanger their lives.
The implementation of an educational and training programme in the mine with a specific focus on creating a culture of safety among miners and more focus on safe working conditions can therefore help overcome the challenges of non-compliance [55, 56]. Moreover, since the mining environment is considered hazardous, all the mining organization needs to conduct medical surveillance as a primary preventative strategy as stipulated by Mine Health and Safety Act (29 of 1996) [12]. The medical surveillance is done before employment, annually or bi- annually and when the miner leaves the company, this is done according to the exposure levels in a different occupation and remedial actions are initiated based on the fitness status [28].
In secondary prevention, the main aim of occupational health is to diminish the impact of sickness or injury that has effectively occurred [47]. Additionally, this level of prevention put more emphasis on reinforcement and decreasing the reaction to the occupational disease or illness caused by the mining environment, thereby intensifying resistance through the provision of treatment [55]. This is achieved by distinguishing and regarding illness or injury at the earliest opportunity to end or slow its progression, encouraging safety strategies to prevent re- injury or recurrence, and implementing programs to return people to their original health and function to prevent long-term problems [56]. The secondary interventions include a regular medical examination and screening tests such as audiometry, spirometry, and vision screening. During the screening process, once the deterioration is identified further interventions such as referral to the specialist and recommendations for the removal of a miner to the occupation which will not have a further effect on the identified problem are done. The chronic disease management programme also forms part of the primary prevention strategy by constantly monitoring compliance through blood pressure and blood glucose monitoring to ensure compliance. Moreover, secondary prevention also included the advocacy to place a miner in a suitably modified work so injured or ill workers can return safely to their jobs [56].
In occupational health, tertiary anticipation intends to diminish the effect of a continuous sickness or injury that has enduring impacts. This is finished by assisting individuals with overseeing long-haul, frequently complex medical issues and injury (for example ongoing sicknesses, long-lasting impedances) to work on however much as could reasonably be expected their capacity to work, their satisfaction, and their future [56]. Secondary prevention activities in the mining environment include a Hearing conservation program to support and rehabilitate those who have already lost their hearing due to noise exposure. These activities include modification of personal protective equipment, job placement to a less noisy area zone. The miners are also referred to a different specialists such as the audiologist, occupational speech therapy for rehabilitation purposes. This assists the miners to adapt to new jobs and also in their changed health status so that they can cope.
The results of this review revealed that there are limited studies addressing the interventions to improve safety compliance. Furthermore in South Africa though there are several legislations to guide in safety and health compliance is still documented as poor with more focus on production. This review also demonstrated that combination of primary, secondary, and tertiary mediations is fundamental to accomplish a significant level of prevention and adherence in mining safety. The role of the OSH professional within the mining organization focusing more on addressing the challenges of none adherence requires further attention. None of the studies identified in the present review focused on the role of the OSH professional in ensuring compliance with the health and safety standards. Occupational health and safety is a human right issue that has got to be given legal, social, and ethical concerns. In SA there’s a requirement for the SA mining business to make an OHS culture that’s strong enough to manage most of OHS problems at each the national and sector levels.
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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In addition, the postharvest conditions may modify several phytochemical substances. Phenolic compounds are referred to as phytochemicals found in a large number of foods and beverages. The relative high diversity of these molecules produced by plants must be taken into account when methods of preparation are employed to obtain industrial or homemade products. Phenolic compounds comprise one (phenolic acids) or more (polyphenols) aromatic rings with attached hydroxyl groups in their structures. Their antioxidant capacities are related to these hydroxyl groups and phenolic rings. Despite the antioxidant activity, they have many other beneficial effects on human health. However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",book:{id:"5609",slug:"phenolic-compounds-biological-activity",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Biological Activity"},signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",middleName:null,surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",middleName:null,surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",middleName:null,surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",middleName:null,surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",middleName:null,surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}]}],mostDownloadedChaptersLast30Days:[{id:"53973",title:"Phenolic Compounds in Water: Sources, Reactivity, Toxicity and Treatment Methods",slug:"phenolic-compounds-in-water-sources-reactivity-toxicity-and-treatment-methods",totalDownloads:7253,totalCrossrefCites:74,totalDimensionsCites:158,abstract:"Phenolic compounds exist in water bodies due to the discharge of polluted wastewater from industrial, agricultural and domestic activities into water bodies. They also occur as a result of natural phenomena. These compounds are known to be toxic and inflict both severe and long‐lasting effects on both humans and animals. They act as carcinogens and cause damage to the red blood cells and the liver, even at low concentrations. Interaction of these compounds with microorganisms, inorganic and other organic compounds in water can produce substituted compounds or other moieties, which may be as toxic as the original phenolic compounds. This chapter dwells on the sources and reactivity of phenolic compounds in water, their toxic effects on humans, and methods of their removal from water. Specific emphasis is placed on the techniques of their removal from water with attention on both conventional and advanced methods. Among these methods are ozonation, adsorption, extraction, photocatalytic degradation, biological, electro‐Fenton, adsorption and ion exchange and membrane‐based separation.",book:{id:"6029",slug:"phenolic-compounds-natural-sources-importance-and-applications",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Natural Sources, Importance and Applications"},signatures:"William W. Anku, Messai A. Mamo and Penny P. Govender",authors:[{id:"195237",title:"Dr.",name:"Messai",middleName:"A.",surname:"Mamo",slug:"messai-mamo",fullName:"Messai Mamo"},{id:"196465",title:"Dr.",name:"William Wilson",middleName:null,surname:"Anku",slug:"william-wilson-anku",fullName:"William Wilson Anku"},{id:"196466",title:"Dr.",name:"Penny",middleName:null,surname:"Govender",slug:"penny-govender",fullName:"Penny Govender"}]},{id:"53128",title:"Phenolic Compounds: Functional Properties, Impact of Processing and Bioavailability",slug:"phenolic-compounds-functional-properties-impact-of-processing-and-bioavailability",totalDownloads:9318,totalCrossrefCites:75,totalDimensionsCites:142,abstract:"In this chapter, we discuss the influence of the processing methods on the content of phenolic compounds in fruits and vegetables. The intake of fruits and vegetables based‐foods are associated with delayed aging and a decreased risk of chronic disease development. Fruits and vegetables can be consumed in natura, but the highest amounts are ingested after some processing methods, such as cooking procedures or sanitizing methods. These methods are directly methods are directly related to alteration on the phenolic content. In addition, the postharvest conditions may modify several phytochemical substances. Phenolic compounds are referred to as phytochemicals found in a large number of foods and beverages. The relative high diversity of these molecules produced by plants must be taken into account when methods of preparation are employed to obtain industrial or homemade products. Phenolic compounds comprise one (phenolic acids) or more (polyphenols) aromatic rings with attached hydroxyl groups in their structures. Their antioxidant capacities are related to these hydroxyl groups and phenolic rings. Despite the antioxidant activity, they have many other beneficial effects on human health. However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",book:{id:"5609",slug:"phenolic-compounds-biological-activity",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Biological Activity"},signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",middleName:null,surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",middleName:null,surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",middleName:null,surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",middleName:null,surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",middleName:null,surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}]},{id:"45635",title:"Application of Cellulose and Cellulose Derivatives in Pharmaceutical Industries",slug:"application-of-cellulose-and-cellulose-derivatives-in-pharmaceutical-industries",totalDownloads:10313,totalCrossrefCites:54,totalDimensionsCites:130,abstract:null,book:{id:"3173",slug:"cellulose-medical-pharmaceutical-and-electronic-applications",title:"Cellulose",fullTitle:"Cellulose - Medical, Pharmaceutical and Electronic Applications"},signatures:"Javad Shokri and Khosro Adibkia",authors:[{id:"140056",title:"Prof.",name:"Javad",middleName:null,surname:"Shokri",slug:"javad-shokri",fullName:"Javad Shokri"}]},{id:"57200",title:"Introductory Chapter: Principles of Green Chemistry",slug:"introductory-chapter-principles-of-green-chemistry",totalDownloads:2781,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"6067",slug:"green-chemistry",title:"Green Chemistry",fullTitle:"Green Chemistry"},signatures:"Hosam El-Din Mostafa Saleh and M. Koller",authors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"},{id:"218817",title:"Dr.",name:"Martin",middleName:null,surname:"Koller",slug:"martin-koller",fullName:"Martin Koller"}]},{id:"66517",title:"Microbial Cellulases: An Overview and Applications",slug:"microbial-cellulases-an-overview-and-applications",totalDownloads:3507,totalCrossrefCites:38,totalDimensionsCites:82,abstract:"Cellulases are a complex group of enzymes which are secreted by a broad range of microorganisms including fungi, bacteria, and actinomycetes. In the natural environment, synergistic interactions among cellulolytic microorganisms play an important role in the hydrolysis of lignocellulosic polymer materials. In fact, it is the combined action of three major enzymes which determines the efficiency of this process. They are exoglucanases, endoglucanases, and β-glucosidase. Microorganisms produce these enzymes in a diverse nature which determines their efficiency in cellulose hydrolysis. During the cellulose degradation reaction, the enzyme targets the β-1,4-linkages in its polymeric structure. This is an essential ecological process as it recycles cellulose in the biosphere. The application of this same scenario for industrial purposes is identified as an emerging area of research. Biofuel production, textile polishing and finishing, paper and pulp industry, and lifestyle agriculture are among the key areas where cellulase enzyme shows a broader potential. The objective of this chapter is to discuss the structure, function, possible applications, as well as novel biotechnological trends of cellulase enzymes. Furthermore, possible low-cost, enzymatic pretreatment methods of lignocellulosic material in order to use it as an efficient raw material for biofuel production will be discussed.",book:{id:"7363",slug:"cellulose",title:"Cellulose",fullTitle:"Cellulose"},signatures:"Sandhya Jayasekara and Renuka Ratnayake",authors:null}],onlineFirstChaptersFilter:{topicId:"85",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82029",title:"Synthesis, Characterization and Antimicrobial Properties of Novel Benzimidazole Amide Derivatives Bearing Thiophene Moiety",slug:"synthesis-characterization-and-antimicrobial-properties-of-novel-benzimidazole-amide-derivatives-bea",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.104908",abstract:"In the present investigation, novel amide derivatives of benzimidazole (4a-f) with different thiophene acids (a-f) coupled in the presence of 1-[Bis (dimethylamino) methylene]-1H-1, 2, 3-triazolo [4, 5-b] pyridinium 3-oxide hexafluorophosphate (HATU) reagent at room temperature and as-synthesized derivatives were characterized by (1H-NMR and 13C-NMR) proton and carbon magnetic resonance, and high-performance liquid chromatography (HPLC) analytical techniques. The amide derivatives were tested for in vitro antimicrobial and antifungal activity and ciprofloxacin was used as standard. The antifungal activity was tested with Carbendazim and Fenbendazole cell lines using clotrimazole standard drug. The results indicated the potential activity toward S. bacillus with compounds having IC 50 of 4 (a), 4 (b), 4 (d) and 4 (e) against antimicrobial strains with IC50 of 51.8 μm, 57.4 μm, 54.5 μm and 56.5 μm respectively. However, compounds 4 (a), 4 (c) and 4 (d) showed greater inhibitions against Carbendazim fungal cell line with IC50 of 22.9, 26.8 and 28.8 μm. On the other hand IC50 values of the Fenbendazole for compounds 4 (a), 4(c) and 4 (d) were found to be 12.7, 10.2 and 12.7 μm, respectively. The thiophene-substituted benzimidazole amide derivatives are the potential candidate drug for antibacterial and antifungal activity.",book:{id:"10840",title:"Benzimidazole",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg"},signatures:"Vinayak Adimule, Pravin Kendrekar and Sheetal Batakurki"},{id:"80168",title:"Benzimidazole: Pharmacological Profile",slug:"benzimidazole-pharmacological-profile",totalDownloads:83,totalDimensionsCites:0,doi:"10.5772/intechopen.102091",abstract:"Benzimidazole is a bicyclic heterocyclic aromatic compound in which benzene fused to imidazole moiety. Benzimidazole holds a vital role in the field of medicinal chemistry which possesses wide variety of pharmacological activities like antibacterial, anti cancer, antifungal, antileishmanial, anti tubercular, anti viral and anti malarial respectively, hence the benzimidazole moiety attracting the medicinal chemist to synthesize the different benzimidazole derivatives with wide variety of pharmacological activities. The book chapter mainly discussed the anti cancer, anti HIV, antileishmanial and anti tubercular activites of recently synthesized benzimidazole derivatives.",book:{id:"10840",title:"Benzimidazole",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg"},signatures:"Mahender Thatikayala, Anil Kumar Garige and Hemalatha Gadegoni"},{id:"80130",title:"Exploring the Versatility of Benzimidazole Scaffolds as Medicinal Agents: A Brief Update",slug:"exploring-the-versatility-of-benzimidazole-scaffolds-as-medicinal-agents-a-brief-update",totalDownloads:60,totalDimensionsCites:0,doi:"10.5772/intechopen.101942",abstract:"Benzimidazole, one of the finest classes of heterocyclic aromatic compounds have the characteristic structure of benzene fused with a five-membered imidazole ring. Despite being made their first appearance in the late 1870s, they are considered as a ‘privileged molecule’. The applications of this wonder molecule range from medicinal chemistry to material science. Benzimidazole being a potent inhibitor for various enzymes has got therapeutic effects like anticancer, antimicrobial, anthelmintic, antioxidant, anticonvulsant, antifungal, anti-inflammatory, antiviral, antihistaminic, antipsychotic, etc. It has also made its existence in various branches of medical science viz ophthalmology, neurology, cardiology and more. The applications of benzimidazole are not only limited to the biological field but also expanded to the field of material chemistry as well. This chapter summarizes the pharmacological properties of benzimidazole, illustrated on numerous derivatives since 2016.",book:{id:"10840",title:"Benzimidazole",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg"},signatures:"Gopakumar Kavya and Akhil Sivan"},{id:"79964",title:"The Anticancer Profile of Benzimidazolium Salts and Their Metal Complexes",slug:"the-anticancer-profile-of-benzimidazolium-salts-and-their-metal-complexes",totalDownloads:95,totalDimensionsCites:0,doi:"10.5772/intechopen.101729",abstract:"Cancer is the most lethal ailment throughout the world in the present era. The development of new anticancer remedies with minor unhealthful effects and an alternate mechanism is crucial. Benzimidazole is a distinguished heterocyclic compound and is now recognized as the privileged scaffold for new drug discovery. This chapter deals with the anticancer capability of benzimidazolium salts and their metal complexes. The benzimidazolium derivatives have been prepared by the introduction of aliphatic and aromatic groups at two nitrogen atoms of the benzimidazole ring. Other modifications include hybridization with other pharmacophores and the preparation of metal complexes. The potent derivatives presented in this review can serve as novel drug candidates against cancer.",book:{id:"10840",title:"Benzimidazole",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg"},signatures:"Imran Ahmad Khan, Noor ul Amin Mohsin, Sana Aslam and Matloob Ahmad"},{id:"79835",title:"Advances of Benzimidazole Derivatives as Anticancer Agents: Bench to Bedside",slug:"advances-of-benzimidazole-derivatives-as-anticancer-agents-bench-to-bedside",totalDownloads:124,totalDimensionsCites:0,doi:"10.5772/intechopen.101702",abstract:"Benzimidazole is one of the privileged nitrogen-containing scaffolds known for its versatile diversified role in insecticides, pesticides, dyes, pigments and pharmaceuticals. Due to its electron-rich environment, structural features and binding potency of various therapeutic targets, benzimidazole derivatives exhibit a broad spectrum of biological activity that majorly includes antimicrobial, antifungal, analgesics, anti-diabetic and anticancer agents. Several benzimidazole scaffolds bearing drugs are clinically approved; they are used for various indications. For example, Bilastine, Lerisetron, Maribavir and Nocodazole are the most widely used benzimidazole-based marketed drugs available as an antihistamine, antiviral and antimitotic agent, respectively. Another example is the recently approved anticancer drug Binimetinib and Selumetinib, which are indicated for BRAF mutated melanoma and plexiform neurofibromas. Not only this, many benzimidazole-based anticancer drugs are in late phases of clinical development. Due to the vast therapeutic potential of benzimidazole scaffold in cancer research, medicinal chemists have gained a lot of attraction to explore it more and develop novel, highly effective and target-specific benzimidazole-based potential anticancer drugs.",book:{id:"10840",title:"Benzimidazole",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg"},signatures:"Kashif Haider and Mohammad Shahar Yar"},{id:"65119",title:"Introductory Chapter: Polyaniline - From Synthesis to Practical Applications",slug:"introductory-chapter-polyaniline-from-synthesis-to-practical-applications",totalDownloads:966,totalDimensionsCites:2,doi:"10.5772/intechopen.83397",abstract:null,book:{id:"7503",title:"Polyaniline - From Synthesis to Practical Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7503.jpg"},signatures:"Florin Nastase"}],onlineFirstChaptersTotal:6},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:317,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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