Natural products against fungal growth.
\\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:"296",leadTitle:null,fullTitle:"Developments in Heat Transfer",title:"Developments in Heat Transfer",subtitle:null,reviewType:"peer-reviewed",abstract:"This book comprises heat transfer fundamental concepts and modes (specifically conduction, convection and radiation), bioheat, entransy theory development, micro heat transfer, high temperature applications, turbulent shear flows, mass transfer, heat pipes, design optimization, medical therapies, fiber-optics, heat transfer in surfactant solutions, landmine detection, heat exchangers, radiant floor, packed bed thermal storage systems, inverse space marching method, heat transfer in short slot ducts, freezing an drying mechanisms, variable property effects in heat transfer, heat transfer in electronics and process industries, fission-track thermochronology, combustion, heat transfer in liquid metal flows, human comfort in underground mining, heat transfer on electrical discharge machining and mixing convection. The experimental and theoretical investigations, assessment and enhancement techniques illustrated here aspire to be useful for many researchers, scientists, engineers and graduate students.",isbn:null,printIsbn:"978-953-307-569-3",pdfIsbn:"978-953-51-4433-5",doi:"10.5772/822",price:159,priceEur:175,priceUsd:205,slug:"developments-in-heat-transfer",numberOfPages:702,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"06bca9a8a622c1fa728dc3943bff471e",bookSignature:"Marco Aurélio dos Santos Bernardes",publishedDate:"September 15th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/296.jpg",numberOfDownloads:147968,numberOfWosCitations:201,numberOfCrossrefCitations:84,numberOfCrossrefCitationsByBook:10,numberOfDimensionsCitations:214,numberOfDimensionsCitationsByBook:11,hasAltmetrics:1,numberOfTotalCitations:499,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 3rd 2010",dateEndSecondStepPublish:"December 1st 2010",dateEndThirdStepPublish:"April 14th 2011",dateEndFourthStepPublish:"May 7th 2011",dateEndFifthStepPublish:"July 6th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"6625",title:"Dr.",name:"Marco Aurelio",middleName:null,surname:"Dos Santos Bernardes",slug:"marco-aurelio-dos-santos-bernardes",fullName:"Marco Aurelio Dos Santos Bernardes",profilePictureURL:"https://mts.intechopen.com/storage/users/6625/images/184_n.jpg",biography:"Dr.-Ing. Marco Aurélio dos Santos Bernardes serves as a postdoc researcher at the Centre de Recherche Public Henri Tudor in Luxembourg. His expertise is in the area of energy analysis, life cycle assessment, renewable energy and biofuels. Dr.-Ing. Bernardes has had 10 papers published in journals such as Solar Energy, International Journal of Life Cycle Assessment, ASME Heat Transfer, a book and book chapters as well. Dr.-Ing. Bernardes' areas of interest include CFD, heat transfer modelling, Solar Chimney Power Plants, thermal processes, thermodynamics. He received his Ph.D. in Mechanical Engineering at Stuttgart University in Germany and conducted a postdoctoral research at the Stellenbosch University in South Africa. He was awarded with the UNEP/SETAC Life Cycle Assessment Award for LCA Projects in Development Countries. Dr.-Ing. Bernardes served as a full professor in the Department of Mechanical Engineering at CEFET-MG in Belo Horizonte for more than 13 years.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Luxembourg Institute of Science and Technology",institutionURL:null,country:{name:"Luxembourg"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"826",title:"Thermal Engineering",slug:"mechanical-engineering-thermal-engineering"}],chapters:[{id:"19881",title:"Thermal Effects in Optical Fibres",doi:"10.5772/22812",slug:"thermal-effects-in-optical-fibres",totalDownloads:9411,totalCrossrefCites:5,totalDimensionsCites:8,hasAltmetrics:0,abstract:null,signatures:"Paulo André, Ana Rocha, Fátima Domingues and Margarida Facão",downloadPdfUrl:"/chapter/pdf-download/19881",previewPdfUrl:"/chapter/pdf-preview/19881",authors:[{id:"49291",title:"Dr.",name:"Paulo",surname:"André",slug:"paulo-andre",fullName:"Paulo André"},{id:"52660",title:"MSc.",name:"Ana",surname:"Rocha",slug:"ana-rocha",fullName:"Ana Rocha"},{id:"52661",title:"Dr.",name:"Maria",surname:"Domingues",slug:"maria-domingues",fullName:"Maria Domingues"},{id:"52662",title:"Prof.",name:"Margarida",surname:"Facão",slug:"margarida-facao",fullName:"Margarida Facão"}],corrections:null},{id:"19882",title:"Heat Transfer for NDE: Landmine Detection",doi:"10.5772/22533",slug:"heat-transfer-for-nde-landmine-detection",totalDownloads:2299,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Fernando Pardo, Paula López and Diego Cabello",downloadPdfUrl:"/chapter/pdf-download/19882",previewPdfUrl:"/chapter/pdf-preview/19882",authors:[{id:"48073",title:"Dr",name:"Fernando",surname:"Pardo Seco",slug:"fernando-pardo-seco",fullName:"Fernando Pardo Seco"},{id:"54002",title:"Dr.",name:"Paula",surname:"López Martínez",slug:"paula-lopez-martinez",fullName:"Paula López Martínez"},{id:"54003",title:"Prof.",name:"Diego",surname:"Cabello Ferrer",slug:"diego-cabello-ferrer",fullName:"Diego Cabello Ferrer"}],corrections:null},{id:"19883",title:"The Heat Transfer Enhancement Analysis and Experimental Investigation of Non-Uniform Cross-Section Channel SEMOS Heat Pipe",doi:"10.5772/22494",slug:"the-heat-transfer-enhancement-analysis-and-experimental-investigation-of-non-uniform-cross-section-c",totalDownloads:2986,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Shang Fu-Min, Liu Jian-Hong and Liu Deng-Ying",downloadPdfUrl:"/chapter/pdf-download/19883",previewPdfUrl:"/chapter/pdf-preview/19883",authors:[{id:"47913",title:"Dr.",name:"Fu-Min",surname:"Shang",slug:"fu-min-shang",fullName:"Fu-Min Shang"},{id:"136296",title:"Prof.",name:"Jian-Hong",surname:"Liu",slug:"jian-hong-liu",fullName:"Jian-Hong Liu"},{id:"136297",title:"Dr.",name:"Deng-Ying",surname:"Liu",slug:"deng-ying-liu",fullName:"Deng-Ying Liu"}],corrections:null},{id:"19884",title:"Magneto Hydro-Dynamics and Heat Transfer in Liquid Metal Flows",doi:"10.5772/23441",slug:"magneto-hydro-dynamics-and-heat-transfer-in-liquid-metal-flows",totalDownloads:3548,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:null,signatures:"J. 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Aflatoxins are a group of toxic secondary metabolites synthesized by fungi of the
Aflatoxins were first identified in 1960 in England as the cause of the Turkey X disease [6]. There are four major aflatoxins produced in nature: B1, B2, G1, and G2. They are named based on their fluorescence under ultraviolet light, and their relative mobility in thin‐layer chromatography on silica gel. Most
Aflatoxins are the most potent naturally occurring toxins and liver carcinogens known, and their contamination of food is a significant risk factor for human health, particularly in developing countries that lack detection, monitoring, and regulating measures to safeguard the food supply. It has been reported that approximately 4.5 billion people living in developing countries are chronically exposed to uncontrolled amounts of aflatoxins [7]. Long‐term low‐dose dietary exposure to aflatoxins is also a major risk for hepatocellular carcinoma. Aflatoxins have been designated as human liver carcinogens by the International Agency for Research on Cancer [8]. Therefore, the control and elimination of aflatoxigenic fungi and aflatoxins in food have great significance. To minimize potential exposure to aflatoxins, maximum levels of aflatoxins have been established by different countries [9]. The U.S. Food and Drug Administration specified a maximum of 20 ppb total aflatoxins for interstate trading of food and feedstuffs and 0.5 ppb aflatoxin M1 in milk. The European Commission has set the limits on cereals and derived products at 4 ppb for total aflatoxins and 2 ppb for aflatoxin B1, and for nuts and dried fruits subject to further processing at 10 ppb for total aflatoxins and 5 ppb for aflatoxin B1. The Korea Ministry of Food and Drug Safety imposed limits for aflatoxin B1 of 10 ppb and total aflatoxins of 15 ppb.
Chemical and physical approaches are widely used to minimize the risk of aflatoxin contamination of food. These are usually focused on inhibiting the development of spores and mycelia, and/or inactivation of aflatoxins by their transformation to nontoxic compounds. The most common methods include the use of synthetic fungicides, X‐radiation, dehulling or cooking processes, and control of environmental factors during harvest and storage [10, 11]. These strategies are usually expensive, time‐consuming, and inefficient. Some of them also cause major changes in the physical properties of food and a serious loss of nutritive value and therefore are inappropriate to eliminate aflatoxins from food [12]. Synthetic chemicals are still the most widely used recourse to prevent fungal contamination of food crops. However, there are strict regulations on chemical compound use in food, and there is political pressure to remove hazardous chemicals from the market [13]. In addition to these limitations, the application of synthetic fungicides can also give rise to notable drug resistance and serious environmental and health problems [14]. Awareness of these problems has led to an urgent need to identify safer alternative strategies.
Natural products are chemical compounds or substances produced by a living organism, and their use as biocontrol agents provides an opportunity to avoid synthetic fungicides. Over the years, efforts have been made to identify new antifungal materials from natural sources for controlling aflatoxin contamination of food [15]. Many bacteria, fungi, and plants that share ecological niches with and encounter aflatoxigenic fungi have the ability to synthesize compounds that inhibit aflatoxin synthesis or remove aflatoxins from food without significant losses in nutritive value; they therefore could be used to replace or complement conventional strategies. Basically, there are three possible ways of using natural products to avoid the harmful effects of aflatoxin contamination of food and feed: (1) prevent and control aflatoxigenic fungus contamination (fungal growth inhibition), (2) inhibit aflatoxin biosynthesis (aflatoxin production inhibition), and (3) decontamination of aflatoxin‐containing food and feed (aflatoxin detoxification). These microbial metabolites and plant constituents are natural products and therefore are desirable for use in food because they can be easily degraded in nature. A variety of naturally derived compounds have been studied for their antifungal and antiaflatoxigenic activities, many of which have shown great potential for controlling aflatoxin contamination. The objective of this chapter is to present the results of studies of the control of aflatoxin contamination using natural products from bacteria, fungi, and plants.
Fungi of
Target of action | Antifungal product | Source | Activity against | Reference |
---|---|---|---|---|
Conidia production and/or germination | [16] | |||
Aldehydes (C6) | Plants1 | [17] | ||
(E)‐Anethole, p‐anisaldehyde, carvacrol, (−)‐carvone, 1,8‐cineole, (+)‐limonene, myrcene, (±)‐α‐phellandrene, (±)‐α‐pinene | Plants | [18] | ||
Benzaldehyde | Plants | [19] | ||
Chitosan | Plants | [20] | ||
Fusapyrone | [21] | |||
1‐Octen‐3‐ol | [22] | |||
Terpenoid | [23] | |||
Membrane formation and/or integrity | Brefeldin A | [24] | ||
Carvacrol, thymol | Plants | [25] | ||
Clove essential oil | [26] | |||
Defensins | Plants | [27] | ||
Eugenol, methyl eugenol | Plants | [28] | ||
Geraniol | Plants | [29] | ||
[30] | ||||
Osmotin | Tobacco | [31] | ||
Phytochemicals | [32] | |||
Zeamatin | [33] | |||
Cell organelles function | Cruentaren | [34] | ||
Defensin | Plants | [35] | ||
[36] | ||||
Haliangicin | [37] | |||
Phytoalexins | [38] | |||
Plagiochin E | [39] | |||
Pyrrolnitrin | [40] | |||
[41] | ||||
UK‐2A, UK‐3A | [42] |
Natural products against fungal growth.
1 Natural product exists in different plants.
The use of bacteria is a promising solution to alleviate fungal contamination in food. In recent years, the study and application of antifungal bacteria has received strong interest. Significant progress has been reported on the isolation and characterization of antifungal compounds. Various bacterial compounds including organic acids, phenyllactic acids, reuterin, and cyclic dipeptides, proteinaceous compounds, and fatty acids have been reported to be able to inhibit the growth of aflatoxigenic fungi (Table 2).
Strain | Activity against | Inhibitory compound | Target of action | Reference |
---|---|---|---|---|
Amblyone | Unknown | [43] | ||
Bacillomycin D | Conidial germination | [44] | ||
Cyclic polypeptide | Unknown | [45] | ||
Iturin A | Cell surface hydrophobicity | [46] | ||
Iturin‐like compound | Conidial germination | [47] | ||
Monorden, monocillin IV, cerebrosides | Unknown | [48] | ||
Proteinaceous | Unknown | [49] | ||
Heat‐stable low‐molecular weight compounds | Unknown | [50] | ||
Proteinaceous | Unknown | [51] | ||
Proteinaceous | Unknown | [52] | ||
Proteinaceous | Conidial germination | [53] | ||
Proteinaceous | Unknown | [54] | ||
Pafungin | Hyphae lysis | [55] | ||
4′‐Phenyl‐1‐napthyl‐phenyl acetamide | Unknown | [56] | ||
Aflastatin | Unknown | [57] | ||
3‐Phenylpropionic acid | Unknown | [58] |
Antifungal compounds against aflatoxigenic fungi growth.
Many bacteria produce organic acids such as lactic, acetic, and propionic acids. The production of these weak organic acids results in an acidic environment that generally restricts the growth of both bacteria and fungi [59]. Phenyllactic acid has been widely reported to have antifungal activities, and its broad‐spectrum antibacterial and antifungal action makes it one of the most extensively studied antifungal organic acids derived from bacteria. Over the last decade, a number of studies have identified phenyllactic acid as the causative agent of antifungal activity. Its lack of toxicity to both animals and humans body, and its lack of any smell make phenyllactic acid a potential candidate for the control of food spoilage [60]. In addition, phenyllactic acid can also play a synergistic role with other metabolites [61, 62]. Reuterin is another antifungal compound produced by bacteria. This low‐molecular‐weight compound has also been reported to possess broad‐spectrum antimicrobial activity. It has been demonstrated to be capable of inhibiting the growth of a wide range of molds including
Fungal metabolites have also been used to reduce aflatoxin contamination in various crops. A recent study showed that culture filtrates of
Plants lack an immune system and must depend on other mechanisms to defend themselves against fungal invaders. One such mechanism is the synthesis of bioactive compounds that act specifically to inhibit fungal growth. Many plant extracts, particularly essential oils, have been reported to possess significant antifungal activity. An extract of
Antifungal peptides and proteins have also been found in insects. Cecropins, originally isolated from the immune hemolymph of the
One important side effect of fungal growth inhibition is the rapid spread of resistant strains. Therefore, inhibitors of aflatoxin production may be a better choice for control and prevention of aflatoxin contamination of food. Current methods to control aflatoxin contamination are mainly based on chemical strategies (pesticides and fungicides). However, the excessive use of chemical treatments has many undesirable consequences: (1) marked pollution of the environment, (2) an increase in resistant pathogen populations, and (3) the presence of chemical residues in food. Specific microbial metabolites and plant constituents have been shown to be effective inhibitors of aflatoxin production without significantly affecting fungal growth; in fact, numerous compounds and extracts possessing inhibitory activity for aflatoxin biosynthesis have been reported. However, tools and techniques have only recently become available to investigate the molecular mechanisms by which these inhibitors regulate aflatoxin biosynthesis [82].
Microbially derived inhibitors of aflatoxin production are of practical use because of their strong activity and the possibility of large‐scale production. For example, a number of
Plant‐derived inhibitors of aflatoxin production have great potential because not only are they highly effective but also the genes responsible for their biosynthesis could be transferred into susceptible host plants to create transgenic plants that resist aflatoxin contamination by
In principle, there are three possible ways to inhibit aflatoxin biosynthesis (Figure 1). First, there can be alteration of the physiological environment or disturbance of the signaling inputs perceived by the fungus. For example, eugenol is a major phenolic component of essential oils extracted from cloves, cinnamon, and nutmeg. It has been shown in multiple experiments to inhibit aflatoxin biosynthesis. Evidence suggests that eugenol inhibits aflatoxin biosynthesis by lowering the physiological requirement for the enzymes activities involved in responding to oxidative stress. Eugenol treatment of fungi growing on Potato Dextrose Agar plates has been shown to result in the reduction of enzyme activities (glutathione peroxidase, microsomal reductases, superoxide dismutase, and xanthine oxidase) involved in responding to oxidative stress, concomitant with the inhibition of aflatoxin production by up to 50% [91]. Zingerone is another plant‐derived aflatoxin inhibitor isolated from certain parts of
Schematic representation of aflatoxin production inhibition by natural products at different levels.
The second way to inhibit aflatoxin biosynthesis is to interfere with the signal transduction networks or gene expression regulation of aflatoxin biosynthesis by, for example, using calmodulin inhibitors, most of which are alkaloid and peptide compounds that have been isolated from a wide variety of natural sources, including many plant species [102]. Multiple lines of evidence support the idea that calcium‐dependent signaling plays an important role in the regulation of aflatoxin biosynthesis [103]. Calmodulin‐binding domains have been identified in the primary sequences of aflatoxin pathway transcriptional regulators (AflR and AflJ) and biosynthetic enzymes, presenting the possibility that calmodulin may influence transcriptional regulation of the aflatoxin biosynthesis gene cluster [104]. Aflastatin A and blasticidin A are well‐known microbial‐derived aflatoxin inhibitors. They are structurally related compounds produced by
The third way to inhibit aflatoxin biosynthesis is to block the activity of aflatoxin biosynthesis‐related enzymes. For example, coumarins have been found to strongly inhibit aflatoxin production without causing significant reductions in fungal growth [108]. It has been suggested that structural similarities between these coumarone and aflatoxins may result in competitive inhibition of biosynthetic enzymes. Terpenoids are a major class of natural products synthesized in plants through the mevalonic acid pathway. There are reports that different terpenoids, including camphene, α‐carotene, limonene, lutein, and zeaxanthin, are inhibitory to aflatoxin biosynthesis in solid or liquid media [113]. The inhibition by terpenoids may occur at the level of whole‐pathway regulation. For example, α‐carotene was found to be able to block the synthesis of norsolorinic acid, the first stable aflatoxin precursor, thereby preventing the accumulation of subsequent pathway intermediates. Caffeine is another well‐studied inhibitor of aflatoxin production, with studies showing that decaffeinated coffee beans and powder support higher aflatoxin production than normal beans and powder, and that incorporation of coffee into growth medium at concentrations of 1% (w/v) inhibits total aflatoxin production by 25%, with no significant reduction in fungal growth. The inhibitory effect of caffeine on glucose uptake is considered to be the possible mode of action for its antiaflatoxigenic activity [114]. Hydroxamic acids, such as 6‐methoxy‐benzoxazolin‐2‐one (MBOA), are also strong inhibitors of aflatoxin biosynthesis. MBOA significantly inhibits α‐amylase induction [115]. It was suggested that the perturbation of sugar utilization by MBOA might be the major reason for its antiaflatoxigenic activity.
Aflatoxins are extremely stable under most conditions encountered during food storage, handling, and processing. Therefore, preventing contamination with aflatoxigenic fungi is the most rational and economic approach for controlling aflatoxin contamination of food. However, detoxification of aflatoxin is required for food already contaminated with aflatoxin. Although various methods have been described for detoxification of aflatoxins in foods, the most commonly used physical and chemical approaches are usually high cost or complex processes, and many also result in nutrient loss and food safety issues.
Biological detoxification of aflatoxins by employing natural products has been shown to be very effective in removing aflatoxin from food. In principle, there are four possible biological approaches to avoid the toxic effects of aflatoxins on the human body: (1) remove aflatoxins through surface adsorption to bacterial or fungal cells; (2) transform aflatoxins into nontoxic compounds by enzymatic degradation; (3) introduce aflatoxin adsorbents into contaminated food and feed to bind the toxins and inhibit their absorption from the gastrointestinal tract; and (4) metabolize aflatoxin into relatively nontoxic compounds via different metabolic pathways (Figure 2).
Schematic representation of aflatoxin reduction with different mode of action. 1 Detoxification in animal body; 2 Detoxification in human body.
Aflatoxin detoxifying microorganisms were first demonstrated in 1996, when Ciegler et al. identified a
Over the last few decades, considerable literature has accumulated that describes methods for removing aflatoxins using different microorganisms. Pure cultures of bacteria and fungi that detoxify aflatoxins, which include
Many reports state that the use of brewer’s yeast cells as an animal feed additive resulted in a reduction in the toxic effects of aflatoxins [123]. In an early study, some yeast strains isolated from West African maize were found to be able to bind 15–60% (w/w) of aflatoxin B1 and this toxin binding was highly strain specific [124]. Yeast cells of
The use of LAB in food fermentation dates back several centuries. Early studies showed that different LABs, including
Enzymatic inactivation of aflatoxins is another attractive strategy for food decontamination. Several microorganisms can transform aflatoxin B1 to aflatoxicol and other less toxic or nontoxic compounds. It has been reported that aflatoxin B1 can be detoxified into aflatoxin B2a during yoghurt fermentation [137]; that aflatoxin B1 is detoxified during fermentation of milk by lactic bacteria [138]; and that
Mycotoxin‐producing fungi are also able to degrade or transform aflatoxins and possibly use them as a source of energy under suitable conditions. Several investigators have observed that aflatoxigenic strains produce large amounts of aflatoxins that usually decrease during continued incubation of the cultures [143].
Another practical approach to reducing the toxicity of aflatoxin to humans and animals is the addition of non‐nutritional inert adsorbents to the diet. These adsorbents sequester the aflatoxins in the gastrointestinal tract, thereby minimizing their toxic effects. Various adsorbents have been tested, including activated carbon, bentonite, cholestyramine, hydrated sodium calcium aluminosilicate, and zeolite, and produced promising results with respect to aflatoxin binding [145]. However, their application in food is limited because of their negative impacts such as reducing nutrient utilization. Therefore, the use of microorganisms and other natural products has become increasingly attractive as a reliable alternative to chemical adsorbents in the gastrointestinal tract.
The potential application of natural products as aflatoxin binders in human foods and animal feeds depends on their stability and the residence time of the complex in the gastrointestinal tract. The adhesion of aflatoxin‐binding microorganisms to intestinal cells appears to be highly strain specific. Yeast cells generally show very low adhesion to the intestine but are capable of withstanding the harsh environment of the gastrointestinal tract [146]. Animal feeding experiments have shown that the addition of whole cells or cell walls of
LAB cells usually show considerably higher adhesion to intestinal cells compared with that of yeast cells. However, it has been reported that aflatoxin binding considerably reduced the adhesive properties of some LAB strains and resulted in the faster excretion of immobilized aflatoxin B1 [149]. Gratz et al. also found that pre‐exposure of the cells of a
Aflatoxins absorbed into the bodies of humans or animals may also be metabolized into relatively nontoxic compounds via different metabolic pathways. The process of detoxification of aflatoxins usually involves removing the double bond of the terminal furan ring or opening the lactone ring. Once the lactone ring is opened, further reactions can occur to alter their binding properties to DNA and proteins [153]. The main reactions of aflatoxin metabolism in humans and animals are hydroxylation, oxidation, and demethylation. There are numerous studies concerning the metabolism of aflatoxin
The preferred strategy for reducing the concentrations of aflatoxins in foods is prevention of aflatoxin formation during preharvest and postharvest of the various susceptible crops. In this context, non‐aflatoxigenic
To achieve effective control of aflatoxin contamination in food, high concentrations of natural compounds are generally needed. The incorporation of natural compounds into packaging materials can be a useful strategy to solve this problem. In the last decade, there have been plentiful studies of the development of active packaging materials. Because the introduction of protective agents in packaging materials can be used to protect food without direct addition of new chemicals, it has received great interest from both the food industry and academic communities. Many natural extracts, such as essential oils and their constituents, are categorized as flavorings in Europe and are categorized as Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. For this reason, they have often been proposed for and used in active packaging. For the purpose of the design of active packaging, it is necessary to establish which compounds have antiaflatoxigenic properties and what concentration is required to obtain maximum inhibition. In addition, because the volatile nature of some components, the release rate of the encapsulated compounds from their polymer matrix should be controlled, thereby magnifying their antiaflatoxigenic action on the product by both direct contact and through the head space of the packaging. The processes of encapsulating natural aflatoxin inhibitors into the polymer matrix should also be carefully controlled. Previous studies have shown notable losses of the active compounds during the film formation step of the casting technique [160].
Nanotechnology‐based systems associated with natural compounds are also a good option. There are many well‐known benefits of associating natural compounds with nanotechnological drug‐delivery systems [161]. One good example is a nanoemulsion: in an emulsified form, natural compounds may be applied as an aqueous‐based treatment. In fact, fine droplets may improve the delivery of inhibitory compounds to cereals because they may be able to penetrate into the cracks and crevices on the cereal surfaces. Nanoemulsions are emulsion droplets with a radius below 100 nm, which can be formed using both high‐energy and low‐energy methods [162]. High‐energy methods require specialized mechanical devices, such as high pressure valve homogenizers, sonicators and microfluidizers. These devices are capable of generating intense mechanical forces that can intermingle and disrupt the oil and water phases. Low‐energy methods rely on the spontaneous formation of nano‐sized oil droplets, which is a physicochemical process that occurs under appropriate conditions with certain combinations of surfactant, oil, and water. The spontaneous emulsification method has recently been reported to be suitable for application in the food industry for fabricating effective antimicrobial nanoemulsions from essential oils [163].
As mentioned previously, genetic engineering is another way to utilize these compounds. Host crop species can be engineered to gain resistance to aflatoxin contamination by incorporation of the genes for biosynthesis of natural inhibitors. There are likely hundreds, if not thousands, of natural compounds that influence aflatoxin biosynthesis at concentrations ranging from submicromolar to millimolar. Unfortunately, many of these inhibitors are not suitable for genetic engineering. The complexity of altering plant natural product pathways makes it difficult to engineer crop species resistant to aflatoxin contamination. In addition, the majority of aflatoxin inhibitors reported so far were tested
In summary, there are various natural compounds that influence aflatoxin contamination in food through different ways, including inhibition of the growth of aflatoxigenic fungi, blocking aflatoxin biosynthesis, and removal or degradation of aflatoxin. These inhibitors are highly promising for the development of new approaches to fighting aflatoxin contamination in food and have the capability to replace or complement conventional strategies. A common feature of many inhibitors is their antioxidant activity; yet, the relationship of antiaflatoxigenic activity and antioxidant activity is unknown. Some inhibitors of aflatoxin production are specifically targeted to the biosynthesis of aflatoxin without affecting the development of the fungal cells. However, most inhibitors also inhibit fungal growth at higher concentrations. This may indicate that secondary metabolism (aflatoxin) is sensitive to stress resulting from low concentrations of growth‐inhibitory compounds. The production of norsolorinic acid, the first stable intermediate in the aflatoxin biosynthetic pathway, was inhibited in parallel with aflatoxin production at the regulatory level of biosynthesis rather than at specific steps within the pathway, indicating the importance of this intermediate. More and more natural inhibitors are being identified, yet the modes of action of most are poorly understood. Further studies are necessary to better understand the mechanisms of action of those compounds before they can be widely used commercially. Using new biological approaches, researchers are now combining datasets from profiling of transcripts, proteins, and metabolites generated using inhibitory compounds with different modes of action, which will provide useful information for dissecting different facets of aflatoxin regulation.
Universities are the core educational institutions of higher education. They convey a wide range of knowledge as a center of academia; teach and research specialized arts and sciences; and develop intellectual, moral, and applied skills (the School Education Act) [1].
Modern universities had their origins in medieval Europe. The oldest university in Europe is said to be the University of Bologna [2] in Italy, which began when a guild of law students organized a “
On the other hand, in Japan, the University of Tokyo was founded in 1877 as the merger and reorganization of Tokyo Kaisei Gakko and Tokyo Medical School [4]. There was no autonomy as in medieval European universities, and it was a powerful state-led bureaucracy training institution. However, in Japan, a bureaucratic training organization called “Daigaku-ryo” had already been established more than a thousand years earlier (670) during the reign of Emperor Tenchi—it was created by the government to learn about the systems and cultures of China and to create an organization as a nation, and it differs greatly from the university organizations in Europe created by the teachers and students themselves [3].
The number of universities doubled from 389 schools (75 national schools, 33 public schools, and 281 private schools) 50 years ago (1971) to 795 schools (86 national schools, 94 public schools, and 615 private schools) as of 2020 (Figure 1), and the number of students also increased, from 1,469,000 to 2,916,000 in 2020. This was greatly influenced by an increase in the population of 18-year-olds. The population peaked in 1966, when the postwar “baby boomer” generation reached the age of 18, at 2.49 million. By 1992, when the generation of their children reached the age of 18, the total stayed fairly steady at 2.05 million. In addition to promoting decentralization, the government announced the deregulation of university establishment standards [5]—that is, the government’s policy of restraining the increase in the capacity of universities and faculties was abolished. As a result, private universities increased from 378 private schools in 1991 to 615 private schools in 2020. The percentage of students advancing to universities has improved dramatically, and the percentage of students advancing to a four-year university reached a record high of 54.4% in 2020, compared with 25.5% in 1991 (Figure 1).
Number of universities and higher education rate in Japan.
Meanwhile, the population of Japan began to decline after peaking in 2008 (128 million people). Due to the declining birthrate, the population of 18-year-olds has continued to decline; it is currently at 1,167,000 (Figure 2). Because of this, and because of the increase in the number of universities due to deregulation, one-third of private universities are under-enrolled [6]. The decline in the quality of university education due to insufficient academic ability and the shortage of students make it difficult for universities to operate. To meet the demands of local communities and society, as well as the diverse needs of students, there should not only be a limited number of universities but many universities should provide education that draws on students’ individuality and attributes, so that a wide variety of educational approaches could be provided in Japan as a whole [7]. For universities to remain seats of learning, teachers and staff should work together to consider their roles, while the administration stabilizes the business foundation.
18-year-old population in Japan.
Modern universities began with the idea envisioned by Wilhelm von Humboldt (1767–1835), the founder of the University of Berlin. He defined universities as institutions that integrate education and research, and emphasized not only lectures but also seminars and practicums, and laboratories of different sorts. That is, he thought that scholarship was something always being produced anew, created by both the professor and the student [3]. This educational philosophy is based in the humanities, and it rejects the idea that vocational education takes precedence over general cultural education. Karl Theodor Jaspers (1883–1969) also described the mission of universities as “the search for truth in a community of researchers and students” [8]. Here as well, research is a basic requirement for universities, and although it is impossible to separate research and teaching, research is regarded as the most important element. In contrast, José Ortega y Gasset (1883–1955) developed a theory of university reform in his book
Kinjo-Yugakkan, which became the basis for Kinjo University, was established in 1904. At that time, there was no school in Ishikawa Prefecture where girls who graduated from higher elementary school could advance to higher education, and to improve girls’ education, Kokichi Kato, a teacher at the prefectural normal school, founded the school with his own money [11]. The educational philosophy of the school was “leading by example,” and “frugality and diligence.” “Leading by example” means doing things before others do, to become a model for such actions, while “frugality and diligence” refer to working and studying hard without extravagances. When it started as a private school, Kinjo-Yugakkan had 29 students, including eight boys. In 1908, a school building was established in Honda-machi, and in 1924, the school was approved as a five-year high school for girls. Furthermore, Kinjo Junior College was founded in 1976. In 1996, the Kinjo Women’s Senior High School was renamed Yugakkan High School and became co-ed.
Kinjo University opened in 2000, and the Faculty of Social Work’s Department of Social Work was established. In 2007, the Department of Physical Therapy was established in the Faculty of Health Services, and in 2013, the Department of Occupational Therapy was added. In addition, in 2015, the Department of Nursing was established in the Faculty of Nursing, and the Graduate School of Rehabilitation was created; with these, Kinjo has become a university specializing in medical and welfare. There are five departments in three faculties, and there are about 1200 students aiming to become medical welfare and childcare/early childcare education professionals. Physical therapists, occupational therapists, nurses, social workers, and care workers are not licensed unless they have taken and passed the national examination. For this reason, medical and welfare universities must provide vocational and professional education also in addition to a liberal arts education and community contributions, which are considered to be the essence of universities.
In reality, since the establishment of our university, many faculty members and students have made social contributions by becoming involved with the community with undergraduate and seminar units. These activities have been useful for regional revitalization and student education, but have rarely led to teachers’ research activities. Therefore, these activities were made into a university-wide initiative, promoting teachers’ research activity. In this era, universities also require “brand power.” The Kinjo Dream Project (KDP) is aimed at developing a system for the promotion of both research and branding by restructuring some established regional collaboration projects while contributing to the community in a more developed manner.
This book therefore focuses on social contribution—one of the proposed roles for universities—and describes the connection between local communities and the social contribution activities that have been carried out over the past 20 years until the establishment of KDP.
The authors have no conflict of interests.
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These side effects are especially noticeable at high doses for prolonged periods. Even in low-dose therapy, glucocorticoids could lead to serious side effects. The underlying molecular mechanisms of side effects of glucocorticoids are complex, distinct, and frequently only partly understood. 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Bioequivalence used to assess the expected in vivo biological equivalence of two proprietary preparations of drug products. If two drugs are bioequivalent, it means that they are expected to be same for all intents and purposes. In determining bioequivalence between two drugs such as a reference drug or brand and potential to be test drug or marketed generic drug. Pharmacokinetic studies are conducted whereby each of the drugs is administered in a cross over study to healthy volunteer’s subjects. Plasma is obtained at regular intervals and assayed for parent drug or metabolite concentration to compare the two drugs. For comparison purpose of two formulations, the plasma concentration data are used to assess key pharmacokinetic parameters. If 90% confidence interval for the ratio of the geometric least square means of peak plasma concentration, area under curve of test and reference drugs are within 80–125%, then bioequivalence will be established.",book:{id:"8331",slug:"pharmaceutical-formulation-design-recent-practices",title:"Pharmaceutical Formulation Design",fullTitle:"Pharmaceutical Formulation Design - Recent Practices"},signatures:"Divvela Hema Nagadurga",authors:null},{id:"68199",title:"Microcrystalline Cellulose as Pharmaceutical Excipient",slug:"microcrystalline-cellulose-as-pharmaceutical-excipient",totalDownloads:3649,totalCrossrefCites:3,totalDimensionsCites:19,abstract:"Microcrystalline cellulose (MCC) is a pure partially depolymerized cellulose synthesized from α-cellulose precursor (type Iβ), obtained as a pulp from fibrous plant material, with mineral acids using hydrochloric acid to reduce the degree of polymerization. The MCC can be synthesized by different processes such as reactive extrusion, enzyme mediated, steam explosion, and acid hydrolysis. It is commonly manufactured by spray-drying the neutralized aqueous slurry of hydrolyzed cellulose. The MCC is a valuable additive in pharmaceutical, food, cosmetic, and other industries. MMC obtained from different sources will differ considerably in chemical composition, structural organization, and physicochemical properties (crystallinity, moisture content, surface area and porous structure, molecular weight, etc.). The high demand of microcrystalline cellulose used in pharmaceutical industries has led to the utilization of locally and naturally occurring materials in the production of microcrystalline cellulose. Many studies on the physicochemical properties of locally produced MCC derived from natural sources have been extensively evaluated in the development of a new natural source for MCC as a substitution of wood, the most abundant one.",book:{id:"8331",slug:"pharmaceutical-formulation-design-recent-practices",title:"Pharmaceutical Formulation Design",fullTitle:"Pharmaceutical Formulation Design - Recent Practices"},signatures:"Anis Yohana Chaerunisaa, Sriwidodo Sriwidodo and Marline Abdassah",authors:null},{id:"53039",title:"Going Small: Using Biophysical Screening to Implement Fragment Based Drug Discovery",slug:"going-small-using-biophysical-screening-to-implement-fragment-based-drug-discovery",totalDownloads:2054,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Screening against biochemical targets with compact chemical fragments has developed a reputation as a successful early‐stage drug discovery approach, thanks to recent drug approvals. Having weak initial target affinities, fragments require the use of sensitive biophysical technologies (NMR, SPR, thermal shift, ITC, and X‐ray crystallography) to accommodate the practical limits of going smaller. Application of optimized fragment biophysical screening approaches now routinely allows for the rapid identification of fragments with high binding efficiencies. The aim of this chapter is to provide an introduction to fragment library selection and to discuss the suitability of screening approaches adapted for lower‐throughput biophysical techniques. A general description of metrics that are being used in the progression of fragment hits, the need for orthogonal assay testing, and guidance on potential pitfalls are included to assist scientists, considering initiating their own fragment discovery program.",book:{id:"5360",slug:"special-topics-in-drug-discovery",title:"Special Topics in Drug Discovery",fullTitle:"Special Topics in Drug Discovery"},signatures:"John J. 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