TLRs cellular expression, binding ligands, signal adaptor & production [2].
\r\n\tb. The growth of digital environments which can educate and empower as well as exploit and destroy (mobile learning, STEM education, tablets, etc.).
\r\n\tc. Social, racial, class, and gender-based discriminations that restrict the developmental potential and the prosperity perspectives
\r\n\td. Health hazards and illnesses such as the laters COVID-19 pandemic.
\r\n\te. Armed conflicts with casualties and displacements of populations seeking refuge
\r\n\tf. Lack of physical spaces that will support and nourish development and learning, etc.
\r\n\tEducation in the post-modern era strives to address the above issues and develop policies, curricula, methodologies, and strategies to contribute to an environmentally and socially sustainable future. It embraces multiple perspectives and worldviews and seeks to touch on inequalities and discriminations in favor of equity. In this direction, children’s s agency lies at the heart of democratic approaches. Educational processes adopt forms of interactions that actualize learning as “becoming” and place it in a continuum between past, present, and future. This book intends to feature innovative approaches that employ transformative elements (targets, methods, materials, ideas, etc.) and embrace the concept of child development as “becoming” in an ever-changing and challenging world.
\r\n\r\n\tWe invite authors to contribute original research or research review papers that present innovative approaches addressing personal and social transformation. All aspects of early childhood education will be considered, including research methodology for the early years.
",isbn:"978-1-80355-949-0",printIsbn:"978-1-80355-948-3",pdfIsbn:"978-1-80355-950-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"351c41dca5c8c997f15e758f2e035178",bookSignature:"Dr. Maria Ampartzaki and Associate Prof. Michail Kalogiannakis",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11281.jpg",keywords:"Early Childhood Education, Preschool, STEAM, Environmental Sustainability, Social Sciences, Social Sustainability, ICT, Digital Devices, Education for Equity, Gender Issues, Post-modern Epistemology, Social Constructivism",numberOfDownloads:65,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 16th 2021",dateEndSecondStepPublish:"December 14th 2021",dateEndThirdStepPublish:"February 12th 2022",dateEndFourthStepPublish:"May 3rd 2022",dateEndFifthStepPublish:"July 2nd 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education.",coeditorOneBiosketch:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool\r\nEducation, University of Crete in Greece. He graduated from the Physics Department\r\nof the University of Crete and continued his post-graduate studies at the University\r\nParis-7 and University Paris-5 and received his Ph.D. degree at the University Paris 5.\r\nHis research interests include science education in early childhood, science teaching\r\nand learning, e-learning, the use of ICT in science education, and games simulations.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}}],coeditorOne:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. 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It is a major threat to food security considering the ever-increasing growth rate in human population which is projected to reach about 10 billion by 2050 [2]. In times of old, forests and marginal lands were converted to farmlands to meet the food demands of the growing population. This practice caused the extinction and endangerment of many plant and animal species; hence it is frowned upon by many stakeholders. As such, today, it would not be prudent to encroach land reserves and other marginal lands for agricultural purposes. It is therefore imperative that we improve soil fertility and health of the available land, to increase food production and to ensure the world’s food security under the current and projected climate change.
Previously, the use of mineral fertilizer was thought of as the most appropriate remedy to soil fertility problems due to its rapid nutrient release [3]. However, mineral fertilizer lacks the ability to improve the soil’s physical properties causing fertility improvement by fertilizers alone to be unsustainable. Over-reliance on mineral fertilizer without due diligence to the organics may lead to increased soil erosion, surface and groundwater contamination, increased greenhouse gas emission and reduced biodiversity [4]. In addition, mineral fertilizers are expensive, and many farmers may not have the purchasing power to acquire it [5]. As a result, the attention of various stakeholders has been drawn to use of organic resources [6]. The application of organic fertilizers presents a more sustainable method of food production. There is unending literature reporting the efficiency and effectiveness of organic nutrient sources in maintaining soil quality (physical, biological and chemical properties), improving crop yields and sustaining productivity [6, 7, 8]. The benefits of applying organic fertilizers to the soil are elaborated in this chapter.
Organic nutrient sources are specifically derived from plant and animal origins [9]. They include plant residues, animal wastes and biofertilizers. In this era where climate change and the COVID-19 pandemic has impacted agricultural production and the financial capabilities of all workforces including farmers, farmers could use organic fertilizers available to them for soil fertility purposes because they are cheaper and more environmentally friendly when they are locally available [10].
Organic fertilizers include poultry manure, cattle manure, green manure (often legumes), field crop residues, composts, bone meal, household waste, blood meal, slurry, cocoa pod husks, palm kernel cake, among others. Biofertilizers are products containing single micro-organisms or combinations of them which when applied help fix atmospheric N, solubilize nutrients, mobilize nutrients, or secrete growth promoting substances to aid crop growth. These products do not supply nutrients themselves but enhance the activities of soil microbes to make more nutrients available to crops. They are categorized into N-fixing biofertilizers, phosphorus solubilizing biofertilizers, composting accelerators and plant growth promoting rhizobacteria [9]. Most of the plant and animal residues are often by-products and nuisance to the environment. Using them as nutrient sources would help reduce waste and greenhouse gas emission.
Organic fertilizers supply all essential crop nutrients (N, P, K, S, Ca, Mg, B, Cl, Cu, Fe, Mn, Mo, Ni and Zn) in balanced forms, including micronutrients. This is often not the case for any one inorganic fertilizer. Since all these nutrients make up the biomass of organic residues, they are released during the decomposition process into the soil. The downside to applying organic fertilizers alone is that they contain very minimal amounts of these nutrients and as such must be applied in bulky quantities to meet crop nutrient demands [11]. Also, the fact that only a fraction of the nutrients in organic fertilizers can be released per season must be factored in when applying organic fertilizers. On the average, as a rule of thumb, only about 50% of nutrients in organic fertilizers are mineralized in the first season of application [12]. Usually, the focal nutrient used to calculate the amount of organic fertilizer to apply is its nitrogen (N) concentration. For example, 30% decomposed cattle manure (DCM) contains about 2% N [13]. Assuming a farmer grows maize, which requires about 90 kg/ha N, that means:
Therefore, to supply 90 kg N = (90 × 100)/2 = 4500 kg DCM.
Since the applied DCM will only supply half the amount of N required in a season, the amount must be doubled to make
To supply same amount of N through mineral fertilizer, a farmer would only need about 200 kg Urea, however, in organic applications, other nutrients are concurrently being applied. Since a large amount of DCM would supply the required N and other nutrients, it must be available to the farmer. Hence advocates of organic fertilizers must emphasize on ways to raise such large amounts of materials for application locally if sole organic production is desired.
Aside the balanced nutrient supply, organic fertilizers add organic matter to the soil if a long-term application is practiced. Organic matter improves the nutrient holding capacity of the soil because it contains organic acids that increase the H+ ions and surface charge of the soil, causing the soil’s cation exchange capacity to increase [15]. Thus, the soil’s ability to hold more cations (nutrients) at exchange sites is increased and hence the nutrient holding capacity of the soil is also improved. Organic matter also improves the buffer capacity of the soil and increases the soil’s ability to resist a change in pH, which in turn affects nutrient loss or gain to the soil [16]. Organic fertilizers increase microbial activity in the soil, causing increased nutrient mineralization rates for the benefit of crops. They stimulate the activities of aerobic and anaerobic bacteria [17] and arbuscular mycorrhizae fungi that form networks of root extension for extensive nutrient availability to crops. Upon the lysis and decomposition of soil microbes, nutrients retained in their biomass are made available in the soil and to crops.
Soil structure, texture, bulk density, and organic matter content are the controls on soil water holding capacity; therefore, any management practice that improves these soil properties, in turn, improves water holding capacity (WHC) of the soil. Soil moisture content is largely dependent on the specific surface area of the soil and the thickness of films of water surrounding the pores [18]. The addition of organic matter through organic fertilizer application improves soil aggregation and increases the surface area of the soil, presenting the soil with more room for soil particles to be surrounded by films of water. As a result, the soil can hold more water against the pull of gravity which drains water from the soil.
While soil organic matter binds soil particles, it also stimulates the activity of soil microfauna whose movement create micro and macropores in the soil, creating extra room for water infiltration [19]. Thus, soil water holding capacity can be improved by the addition of organic fertilizers. In the wake of climate change, where unexpected droughts may be imminent, improving the water holding capacities of the soil with the application of organic fertilizer is the way to go. Also, the physical presence of organic materials on the soil serves as mulch that reduces evaporation and retains moisture in the soil. It also reduces the speed of runoff water and allows rain or irrigation water to infiltrate the soil at favorable speed, thereby reducing erosion, soil and nutrient loss [19].
The soil binding properties of organic matter and improvement in soil aggregation helps to improve soil structure [20]. The addition of organic matter also improves soil texture and aeration. Soils with improved structure and texture allow easy air, water, and root movement to support healthy crop growth.
Many research works have observed extra crop yields with organic fertilizer application compared to when its nutrient equivalents are applied through mineral fertilizer [21, 22, 23]. Various mechanisms have been proposed to explain this added crop yields from organic fertilizer application. Some of which include
Under the improved nutrient synchrony mechanism proposed by Vanlauwe et al. [23], when organic fertilizers are applied, they supply microbes with energy from the carbon they contain, to drive decomposition processes. This leads to temporal immobilization of soil N [24, 25] to build their body tissues. The immobilized N is made available at a later stage of plant growth when the microbes have decomposed the organic material to make nutrients available and/or some microbes have lysed and released their nutrients to the plant when it needs nutrients most. In effect, the peak of nutrient supply coincides with highest crop nutrient demand point when crops have matured, so that the nutrients are efficiently utilized, and little is lost to the environment. Kapkiyai et al. [26] reported that a combination of organic and mineral nutrient sources has been shown to result into synergy and improved synchronization of nutrient release and nutrient demand and uptake by plants leading to higher yields.
The general fertility improvement mechanism [23] is based on the theory that organic matter, aside its addition of nutrients to the soil, improves other physical properties of the soil that helps to perpetuate the nutrient addition effect in real time. Some of these benefits include the improvement of soil structure, water and nutrient holding capacities as discussed above. It also adds micronutrients which is usually not the focus of inorganic fertilizer application.
Priming effect is another mechanism proposed by Kuzyakov et al. [27], in which organic fertilizers affect additional crop yields. Priming refers to strong short - term changes in the turnover of soil nutrients caused by the addition of easily decomposable organic materials. Changes may be positive or negative depending on whether nutrients are rapidly mineralized or immobilized. Under this mechanism, a sum of nutrients available in the soil after harvest and nutrients in crops from the field are higher than a sum of the initial soil nutrients and nutrients in the organic materials. Thus, the additional unaccountable nutrient is the result of organic fertilizer precursing a more rapid mineralization rate and dissolution of previously unavailable/fixed nutrients into solution. This is made effective by the improvement in microbial population, diversity and activity affected by the organic material addition.
These mechanisms, though proposed by different authors, all point to the fact that organic fertilizers are beneficial to the soil and consequently, crops.
Despite the benefits of organic fertilizers to the soil, organic resources application is limited by the large amounts required to meet nutrient demand [28]. Hence locally available organic resources must be used to overcome this limitation. In areas where animal production is common, feedlot manure is the most available organic fertilizer resource. Crop residue retention and cash crop- cover crops rotation is an option to increase on-farm residue production. One other option that has proven to be effective is an integrated nutrient management approach where organic and inorganic fertilizers are applied in right quantities [29]. This approach helps to harness the mechanisms underlying the effects of organic fertilizer application on crops, resulting in synergy in terms of crop yields.
In times when climate change is imminent and its effect on agriculture tends to endanger food security, it is paramount that farmers and other stakeholders use strategies and resources that adapt farming systems to the changing climate. Climate change is mainly driven by natural and anthropogenic activities that pump greenhouse gases (examples CO2, CH4, N2O) into the atmosphere [30, 31]. It may lead to extreme droughts or extreme floods, which may have devastating impacts on food production and agriculture. In this light, organic fertilizers are a great resort due to their replenishing effects on soil physical and chemical properties. Aside the benefits of organic fertilizers discussed above which may adapt the soil to drought conditions, soils should be well drained and loose in flood prone areas in wait of climate change. In compact and poorly drained soils, the addition of organic fertilizers would improve soil particle aggregation and structure to give the soil more room to infiltrate water without settling on the top for too long to cause floods. The addition of organic matter reduces the inventory of greenhouse gasses contributed to climate change by agriculture. This is achieved by the sequestration of carbon into the soil from organic fertilizers applied. The carbon would have been lost to the atmosphere as CO2 or CH4 if it had not been incorporated into the soil [32]. As a result, the application of organic fertilizers to the soil helps to reduce greenhouse gas emission leading to global warming and a consequent climate change and helps adapt the soil to the current and future changes in the climate.
Since organic materials are diverse in type and nutrient composition, it is difficult to give a general recommendation of an organic material. The lignin, polyphenol and nitrogen contents of organic material are important controls on its nutrient mineralization, once applied. It is important to evaluate the carbon to nitrogen (C:N) ratio of an organic material to determine if application of the material will lead to N mineralization or immobilization. A C:N ratio of 25 would enhance decomposition and mineralization by soil microbes while a C:N ratio above that would enhance N immobilization [14]. Hence the lower the C:N ratio, the more rapidly nutrients will be made available to the soil. Organic materials high in lignin (>15%) and polyphenol (>5%) contents usually have high C:N ratios and are resistant to microbial decomposition; hence will decompose slowly. If the N content of the material is 2.5% or more, it would likely decompose and mineralize faster [33].
The effectiveness of an organic material as a fertilizer is also dependent on how it is applied. Surface application of organic fertilizer enhances the loss of N through ammonia volatilization or loss of N and P through runoff and erosion. Judicious methods by which organic materials may be applied to reduce wastage and nutrient losses include band spreading, trailing hose method, burying method, rapid soil incorporation, and the addition of nitrogen inhibitors [34].
Band spreading is the application of the organic material(s) in narrow bands usually a few centimeters away from the crops. This reduces the surface area of the material to the atmosphere so that ammonia volatilization is reduced. To reduce the rate of denitrification as well, band spreading should be done during cool weather with no excessive soil moisture and at right rates. The crop canopies also serve as a physical barrier that further reduces the rate of ammonia volatilization from band spreading applications.
Slurries or liquefied organic fertilizers could be applied in these narrow bands through trailing hoses which hang down from a boom and run along or just above the surface of the soil.
Organic amendments could also be buried at about 5-30 cm depth depending on the crop establishment. Deeper depth burying can be practiced before crops are grown while shallower depth is suited for already established crop fields. This method greatly reduced N loss through ammonia volatilization and the loss of material through erosion.
Manure could be rapidly incorporated into the soil during soil tillage (before planting) or with hand implements to reduce N and P losses in volatilization and runoff.
Under conditions with high denitrification potential, nitrification inhibitors could be added to organic fertilizers to delay the rate at which ammonium is converted to nitrates, which is a suitable substrate that precursors the denitrification process. It is important to apply organic fertilizers at cool times of the day and at the right rates to reduce nutrient losses.
The sole application of organic fertilizers has proved to be a slow means of nutrient supply to the soil. Hence the combined use of organic and inorganic nutrient sources has been proposed [29]. Such applications harness the benefits of synergistic interaction between the organic and inorganic nutrient sources. The main objective of this research was to increase maize yield with the application of organic manure or a combination of it with mineral fertilizer. To arrive at this objective, the yield of maize following varying rates of combined manure and mineral fertilizer applications were estimated at harvest, synergistic benefits of combined applications were quantified and the effect on soil nutrient stocks were analyzed.
A field experiment was conducted at the plantation section of the Kwame Nkrumah University of Science and Technology under rain-fed conditions. Nine treatments (three levels of mineral fertilizer at 0, 50 and 100% of the 90-60-70 kg/ha NPK recommended rate (RR) by three levels of manure at 0, 50, 100% of 5 t/ha RR) were applied on the field in a factorial fashion arranged in Randomized Complete Block Design (RCBD) with three replications. The land was slashed and burned and later plowed and harrowed to a fine tilt. Plot layouts were done with lines and pegs with each plot measuring 3 m by 2 m. There were 2 m alleys between replications and 1 m alleys between plots. Initial soil and manure sampling and analyses were done to characterize them. Randomized manure treatments units were allocated to their designated plots. The Akposoe maize variety developed by the Crops Research Institute of Ghana was planted 2 weeks after manure allocation. Weeding was done manually when necessary. Mineral fertilizer application was done 2 weeks after planting (WAP). The fertilizers were applied as urea, triple superphosphate and murate of potash. The urea was split applied in the first fertilizer application (2 WAP). The other half of the urea was applied 6 WAP. The manure was spread in the plots and raked in to about 5 cm depth. The fertilizer was applied by the band placement method, about 5 cm away from the maize plants. A final soil analysis was done after harvest to determine soil nitrogen (N), phosphorus (P) and potassium (K) levels. Data was subjected to analysis of variance (ANOVA) with the GENSTAT statistical package and significant means were separated with least significant difference at 5%.
Note: Rains were quite erratic at the start of the experiment until an unexpected shortage during the reproductive stage of maize growth. Though unfortunate, this was a good situation to determine if manure applied to the soil would help maintain more soil moisture and consequently impact maize yield.
The lack of rains crippled any effect of the manure alone or its combinations with mineral fertilizer to create differences in the yield of maize. Limited soil moisture has been reported to constraint maize yield [35], because all the processes involved in nutrient movement to roots, uptake by roots and translocation through the transpiration stream use water [36].
After harvest, soil and statistical analysis showed that plots receiving 50 and 100% rates of manure had a significant 20% more total soil N than the control and mineral fertilizer rates. It is possible that due to the rapid nutrient release mechanism of mineral fertilizer, most of its nutrients was released during the early stages of the maize growth, subject to rapid loss from the soil system. The C:N ratio of the manure was 23.08, which is an indication that N was being mineralized [35] into the soil system over a long period, even after the shortage of rains. A combined use of the full rate of manure and full rate of mineral fertilizer also had 20% more total soil N than each individual nutrient source. It is evident that combining organic and inorganic inputs creates a balance between increasing N availability for plant uptake over sole organic application and decreasing N availability for potential system losses compared to fertilizer alone [37].
The rather erratic rains at the beginning of the experiment might have caused soil P and K to leach beyond root zone, hence the lack of differences between the effects of sole manure and mineral fertilizer applications or their combinations at the end of the experiment.
Overall, it was concluded that organic manure had the potential to hold nutrients in the soil longer than inorganic fertilizers. In the advent of climate change, it could be a very useful tool especially in areas was droughts are expected.
Our start point is that: inflammation is known pathogenesis of different pathophysiological conditions and diseases affecting different body tissues whether acute or chronic. Every inflammation involves an immune response -innate and adaptive- that started with specific receptors called recognition receptors to identify stimuli/damage signal, activation of consequence inflammatory pathway/cascade, the release of inflammatory markers, and recruitment of inflammatory immune cells [1].
The innate immune response is initiated by either endogenous ligands acting as damage signals known as the damage-associated molecular pattern (DAMPs), or exogenous pathogenic ligands-that are accurately portion of the pathogenic microorganism- lead to the same fate; damage signals throughout pathogen-associated molecular patterns (PAMPs) [2]. These patterns alter the body of the cell and cause tissue injuries leading to massive necrosis that release intracellular component into surrounding, these components activate TLRs [3, 4]. These processes, which are both the mechanism and the net results of inflammations, infections, or ischemic injuries cause more, harm than the initial causes itself by improper stimulation of the immune response [3, 4].
TLRs are a family of pattern recognition receptors (PPR), which also involves nucleotide oligomerization domain (NOD)-like receptors (NLR) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR). They are located on cell membrane/surface and nucleus, are responsible for the detection/recognition of the pathogen or intracellular damaged derived molecular signals to start immune response [1, 2].
These complicated inflammatory processes induced by the immune system are the “Classical typical scenario” involved in the majority of ischemic events, cancers, infectious and inflammatory diseases [4]. For further information about the immune system, Video 1 (https://youtu.be/8mEnyBdsrr8) can be shown on Armando Hasudungan YouTube channel [2] that would explain the innate immunity link with TLRs.
TLRs are PRR family involves 13 members that exist in mammals with 10 members detected in the human genome [5, 6], depending on their similar morphology with Toll. Toll is a gene product that participate in both embryonic polarity development and adult fly -antimicrobial response of the species
TLRs are expressed in almost all body tissues involved in immunologic response as well as those exposed to external environments like the spleen, blood, lung & gastrointestinal tract [4, 8]. The particular cellular expression involves innate and adaptive immunity as well as different nonimmune cells. TLRs cellular expression involves the white blood cells “the sentinel of the innate immune response”: microphages (MΦ) & mast cell (MC) “innate immune response keys”, dendritic cells (DCs) (primarily pathogenic detector of the adaptive immune response) [4, 6, 8, 9], endothelial cells, epithelial cells, fibroblast, glial cells, astrocytes, oligodendrocytes, etc. [1, 5, 8, 10].
Cellular expression of TLRs family members largely variable and mainly depends on the presence of active infections [8]; according to the same source, as ex., bacterial product & pro-inflammatory cytokines can induce the expression of TL3 while IL-10 blocks TLR4 expression. It has been found that TLR2 expression is more specifically involved in the gram-positive bacteria signaling [8]. TLRs are located either primarily to immune cell plasma membrane phospholipids including TLR 1, 2, 4, 5, 6, & 11 [3, 4, 8]; Or located at the endosomal and lysosomal phospholipids where their extracellular domain (ECD) and its ligand-binding site project into the interior of the organelles like TLR 3, 7, 8, 9, 10 and 13 [2, 3, 10, 11].
TLRs are a type I integral transmembrane glycoprotein family of very conserved structure [5, 7], consist of 700–1100 amino acids [2, 4]. Their structure, shown in Figure 1 consist of 2 domains: an ECD that recognize ligands, consist of repetitive motifs rich with leucine and an intracellular domain (ICD) –called cytoplasmic- that maintain inflammatory signal consequence, the last consist of interleukin (IL)-1 receptor region called Toll/IL receptor (TIR) domain [12, 13].
A representative structure of TLR. The conserved structural features of all TLRs consist of three critical components: (1) leucine-rich repeat (LRR) motif; (2) transmembrane helix; (3) intracellular TIR domain. The LRR structure is based on the model of TLR1-TLR2 heterodimer (Protein Data Bank, PDB, ID: 2z7x) interacting with six triacylated-lipopeptides, Pam3CysSerLys4 (Pam3CSK4), whereas the TIR domain homology model is based on TLR2-TIR structure (PDB ID: 1fyw) [
TLRs involves 13 family members that exist in mammals with 10 members detected in the human genome [5, 6]. Human TLRs amino acids sequence allow a subfamily classification into the TLR2, TLR3, TLR4, TLR5, and TLR9 subfamilies. The TLR2 subfamily involves TLR1, 2, 6, and 10; the TLR9 subfamily involves TLR7, 8, and 9 [14].
TLRs members can form homodimers/heterodimers among their same protein family or associates with an “outside TLR family” protein; both formations contribute to their structural and functional diversity [4]. Homodimers are formed by TLR4 while TLR members 1, 2, and 6 like TLR1/2 or TLR2/6 dimers form heterodimers [2, 3, 15, 16, 17]. TLRs members, their dimerization, cellular distribution, ligands, induced signaling pathway, and product are shown in Table 1; for further information about TLRs, Video 2 (https://youtu.be/8mEnyBdsrr8) about TLR overview can be shown at Armando Hasudungan YouTube channel [18].
TLRs | Immune Cell Expression | PAMPs | DAMPs | Signal Adaptor | Production |
---|---|---|---|---|---|
TLR1+ TLR2 | Cell surface Mo, MΦ, DC, B | Tri-acylated lipoproteins (Pam3CSK4) Peptidoglycans, Lipopolysaccharides | (TLR2 DAMPs listed below) | TIRAP, MyD88, Mal | IC |
TLR2+ TLR6 | Cell surface Mo, MΦ, MC, B | Diacylated lipoproteins (FSL-1) | Heat Shock Proteins (HSP 60, 70, Gp96) High mobility group proteins (HMGB1) Proteoglycans (Versican, Hyaluronic Acid fragments) | TIRAP, MyD88, Mal | IC |
TLR3 | Endosomes B, T, NK, DC | dsRNA (poly (I:C)) tRNA, siRNA | mRNA tRNA | TRIF | IC, type1 IFN |
TLR4 | Cell surface/ endosomes Mo, MΦ, DC, MC, IE | Lipopolysaccharides (LPS) Paclitaxel | Heat Shock Proteins (HSP22, 60, 70,72, Gp96) High mobility group proteins (HMGB1) Proteoglycans (Versican, Heparin sulfate, Hyaluronic Acid fragments) Fibronectin, Tenascin-C | TRAM, TRIF TIRAP, MyD88 Mal | IC, type1 IFN |
TLR5 | Cell surface Mo, MΦ, DC, IE | Flagellin | MyD88 | IC | |
TLR7 | Endosomes Mo, MΦ, DC. B | ssRNA Imidazoquinolin-es (R848) Guanosine analogues (Loxoribine) | ssRNA | MyD88 | IC, type1 IFN |
TLR8 | Endosomes Mo, MΦ, DC, MC | ssRNA, Imidazoquinolines (R848) | ssRNA | MyD88 | IC, type1 IFN |
TLR9 | Endosomes Mo, MΦ, DC, B, T | CpG DNA CpG ODNs | Chromatin IgG complex | MyD88 | IC, type1 IFN |
TLR10 | Endosomes Mo, MΦ, DC | profilin-like proteins | MyD88 | IC |
TLRs family members can recognize two types of associated molecular patterns as their ligands, derived from pathogens or damaged organelles damaged structures.
PAMPs derived from pathogen [5, 19]; like gram-negative bacterial lipopolysaccharides (LPS), gram-positive bacterial lipoteichoic acid (LTA) and peptidoglycan (PGN), mycobacterial lipopeptides, yeast zymosan, viral and bacterial ribonucleic acid (RNA), and unmethylated cytosine phosphate guanine containing- (CpG) deoxyribonucleic acid (DNA) [20, 21].
DAMPs damaged organelles structures, extracellular matrix, cytosolic and nuclear proteins, Heat shock protein-60 (HSP-60) and HSP-70, hyaluronic acid fragments, and free fatty acids (FFA) [5, 22, 23]. They cause activation of the innate and inflammatory immune responses, epithelial regeneration, and sterile inflammation control [6, 24].
Upon TLRs recognition and binding to their ligands, they undergo conformational changes, dimerization as well as interaction with adaptor molecules passing series of intracellular signal transduction pathways that involve transcription factors NF-κB, IRFs, and mitogen-activated protein kinase (MAPK) activation. These pathways finally resulting in the secretion of pro-inflammatory mediators including nitric oxide (NO), CK- like tumour necrosis factor-alpha (TNF-α), IL-6 & IL-1β, chemokines (CC), and type I IFN [15, 21, 25, 26]. As shown in Figure 2.
Signaling pathways of TLR. Surface and endosomal TLRs bind to adaptor molecules and co-receptors. Signal through Myd88 dependent/independent pathway ending with proinflammatory CK or type I IFN [
Co –receptors involved in TLRs signalling include Cluster differential 14 (CD14) and Lymphocyte antigen 96 (MD-2). Both have a major role in TLR4 activation after LPS recognition. CD14 is a glycophosphatidylinositol attached protein expressed on innate immune cells as macrophage and monocytes that function as co-receptor for both cell surface & endosomal expressed TLRs. Lymphocyte antigen 96 (MD-2), which is a cell membrane glycoprotein associated specifically with TLR4 ECD, and expressed at myeloid and endothelial cells [6, 13, 21, 26, 27].
TLRs signaling pathways involves four main adaptor protein molecules: MyD88, TIR domain-containing adaptor protein/MyD88 adaptor-like molecules (TIRAP) also called MAL, TIR domain-containing adaptor protein inducing interferon-β (TRIF), and TRIF related adaptor molecule (TRAM) [13, 21, 28]. TLRs signaling pathways involves activation of five TIR containing adaptor kinase molecules, like IL-1 receptor-associated kinase (IRAK) -1 and 4, TNF receptor-associated factor-6 (TRAF6), serine/threonine binding kinase (TBK)-1, MAPK, and inhibitor of kappa-B (IκB) kinase (IKK) [13, 28].
There are three transcription factors involved in the TLRs signalling pathway including NF-κB, AP1, and IRF. NF-κB is an intracellular pleiotropic protein complex; it is responsible for gene regulation of proinflammatory CK, CC, adhesion molecules, and cell cycle/survival regulating proteins as cyclin D1 and B cell lymphoma 2 (Bcl-2). AP1 is a dimer of both protein Jun and Fos families; that is associated with cell replication and survival regulation. Finally, the IRFs protein regulating IFNs, are responsible for signal stimulation via MyD88independent/TRIF pathway [6, 13].
There are two intracellular signalling pathways for TLRs involve MyD88-dependent/& MyD88-independent also called (TRIF-dependant) signal transduction pathway.
It is utilized by all TLRs but not TLR3 [21, 29]. This pathway activates the IRAKs, TRAF6, transforming growth factor (TGF)-β-activated kinase (TAK)-1 and the IKK complex [15]. It causes the nuclear translocation of NF-κB and adaptor protein-1 (AP1) [28, 30], and ends with the secretion of CK like IL-6, IL-10, IL-12 & TNF-α [16, 29]. MyD88 also stimulate the classical extracellular signal-regulated kinases (MAPK/ERK), phosphoinositide-3 (PI3), and Jun (N)terminal kinase (JNK) which stimulate the AP1 signalling pathway, and induce the interferon regulatory factor-7 (IRF7) ending with the release of type-I IFN or co-stimulatory molecules associated with the antimicrobial response by endosomal TLRs 3, 7, 8 and 9 [13, 29, 31, 32].
The main pathway of TLR3 and 4, involve TRIF signalling pathway activation which involves TRAF6 activation, results in inositol triphosphate-3 (IP3) phosphorylation and induction of IFN-β gene expression as well as activation of TRAF6 [21, 29].
Surprisingly the same outcome was obtained from plasmatoid dendritic cells (pDCs) stimulated by TLR 7& 9 throughout the activation of the MyD88/IRF7 dependent pathway [15, 33].
TLR4 further utilizes TIRAP to activate MyD88 and TRAM to bridge the TRIF activation, which means that TLR4 uniquely utilizes both the MYD88 dependent and independent pathways [11, 21, 29].
As stated by S. Kiziltas et al. “TLR stimulation product is dependent on the nature of PAMPs, the activated TLR, the activated cell and the level of CK. Moreover, the chronically activated signalling pathway would possibly induce transcription of oncogenic factor; adding further complexation to the intracellular signalling for these receptors” [5, 13].
TLRs play an important role in pathophysiological disorders due to their wide tissue distribution, their function as pattern recognition receptors that respond to variable bacterial and damage associated molecules, and involvement in multiple inflammatory signal pathways/& process all render TLRs being a major player in any inflammation-related disorder [4, 5, 6, 19, 22, 23, 34]. In addition, analysis of TLRs gene polymorphism in human disorders revealed an increased risk of bacterial infection and sepsis as an example [34]. This section is a shortcut or summary to TLR involvement in different pathophysiological disorders rather than a full description section.
Inflammation is a common etiology of many disorders and disease including ischemic injuries, microbial infections, diabetes, arthritis and cancer [3, 4, 35]; still, any inflammatory process is triggered by damage signal recognized by pattern receptors and induce activation of signaling pathways leading to the production of pro-inflammatory markers and activation of immune cells [35]. These processes also induce the release of free radicals (FR) such as reactive oxygen species (ROS) and the activation of hypoxia-inducible transcription factor-1 (HIF1), causing tissue stress and reduced tissue oxygen status, so-called tissue hypoxia. Hypoxia is believed to be a hallmark as well as a key trigger of inflammation itself [35, 36].
Under normal conditions HIF1-α subunit (the inducible form of the heterodimer protein HIF-1 transcription complex) [35], is controlled by hydroxylation of proline residue via prolyl hydroxylase enzyme, and breaking down via proteasome. However under inflammatory conditions LPS activate TLRs that stimulates nicotine amide adenine dinucleotide phosphate (NADPH) oxidase (Nox)-associated cross-talk with the MAPK signaling pathways [36, 37], that causes proinflammatory CK & markers production thus increasing mitochondrial FR release like ROS causing more and more tissue stress. That causes HIF1- α activation; here HIF1- α protein inactivation process will be inhibited due to proline consumption, leading to HIF1-α accumulation in MΦ, DCs and other non-immune cells that exposed to hypoxia/ & non-hypoxic damage signals [38]. Furthermore, this would induce metabolic reprogramming of mitochondrial respiration causing succinate release, and production of IL-1β [35, 38].
In dendritic cells, TLRs cause further stabilization of HIF1-α via release of NF-κB, which would further increase glucose uptake and render shifting of mitochondrial respiration to the anaerobic glycolytic pathway due to the increased oxygen demand versus the decreased supply [35, 36]. Finally result in disruption of the normal function of DCs, the primary pathogenic detector of the adaptive immune response; which undergo cellular maturation upon TLRS activation that results in further expression of co-stimulatory molecules, further production of pro-inflammatory CK & CC, and migration to lymph node so to present antigens to naïve T-cells [4, 35]. All these scenarios would further amplify the existing inflammation and tissue damage [35].
HIF1-α is a transcription factor that responsible for cellular adaptive responses after exposure to injury/stress environment, including maintenance like controlling angiogenesis to improve blood vessel formation, shifting cellular mitochondria respiration to anaerobic glycolysis through improving cellular survival and cellular adhesion in oxidative stress environment’s [36]. In addition, it is the major controller of phagocytes bactericidal capacity, and involved in myeloid cell-mediated inflammation, and is an essential factor for inhibition of myeloid cell apoptosis induced by LPS. The last point made it an important factor also in the TLR4 signaling pathway [36, 38]. HIF1-α function as a double-edged sword, that mediate cellular adaptive to stress but progress disease status by the same time [38].
TLRs are expressed in various central nervous system (CNS) cells predominantly in neurons, astrocytes, resident microglia, cerebral microvasculature, plexuses choroid, and leptomeninges. They are associated with the detection of- and regulated by central DAMPs [33]. TLR4 is further upregulated centrally by glutamate via N-methyl-D-aspartate (NMDA) dependent mechanism and peripherally by noradrenaline/β2 receptor, & corticotrophin-releasing factor. TLRs play an important role in restoring central homeostasis, physiology of stress-sensitive behaviour after injuries or diseases as multiple sclerosis, Alzheimer’s, and stroke [33].
In the experimental model of CNS, stress exposure revealed mRNA upregulation and activation of TLRs in the brain frontal cortex after the stress is involved in the loss of neuronal plasticity and survival depending on the activation of NF-κB induced ROS production. Also resultant bacterial translocation from the gut to the systemic circulation and other organs such as the liver, spleen, and mesenteric lymph nodes; These circulating gram-negative bacteria are the major source of LPS, which can activate brain TLR4 through multiple pathways, including a neuroinflammatory response. This is partially explained by the theory known as leaky gut [11, 33].
In another experimental model of neurogenesis, TLR3 & 4 were found to act as down regulators, TLR3 deletion/loss of function was also linked to improved cognitive function. The same reference state an opposed case in viral meningitis when TLR3 & 9 recruitment help to decrease neuronal injury and localize infection area and in Alzheimer disease where TLR2, 4, 5, 7 & 9 were suggested to improve disease progression by inhibiting amyloid plaque accumulation [1].
TLR is thought to play a considerable role in several respiratory disorders starting from allergic rhinitis ending with severe inflammatory disorders like acute respiratory distress syndrome (ARDS), through their activation by the causative inflammations derived by pulmonary oedema, trauma, sepsis & even drug overdose [9, 37]. In allergic rhinitis TLR2, 3, & 4 were found to be both upregulated by- and involved in-the causative inflammation [37].
TLR2 has the mainstay of involvement & determination in respiratory allergic disease due to considerable genetic variation. In asthma, an experimental study shows TLR2 induction by synthetic Pam3Cys triggers immune response & disease severity [37]. While in acute lung injury (ALI) & ARDS, TLR2 was found to be activated by Toll interacting protein (Tollip) [14]. TLR4 was found to increase asthmatics severity & prevalence in paediatrics. TLR4 genetic polymorphism affects cluster differentials (CD)41–251 regulatory T cells (Tregs) which are activated by LPS, the same ligand of TLR4 itself. [2, 3, 37].
An experimental model of doxorubicin and hydrogen peroxide-induced cardiac injury showed TLR2 to be involved in cardio myocytes apoptosis, besides TLR2 targeting suggested to be protective in septic cardiomyopathy [1]. In addition, murine models revealed cardiac tissue expression of TLR4 increased after hypertension, myocardial ischemia, maladaptive left ventricular hypertrophy, and angiotensin II (AngII) infusion participating in vascular remodelling & stiffness, endothelial dysfunction, increase myocardial infarction (MI) size & susceptibility. While Human studies revealed the same in patients with unstable angina, MI, heart failure, atherosclerosis & myocarditis [9, 27, 39, 40, 41].
TLR4 expression & signalling was increased in patients’ monocytes during attacks of unstable angina & MI [37]. In the experimental model & human vascular inflammation, TLR4 was found to increase the production of CK, CC as well as increase TLR2 expression. In the early stage of the atherosclerotic lesion, TLR4 mRNA protein was detected & MyD88 -the mainstay of TLR signalling pathway- gene deficiency was linked to decrement in CK, CC & lipid content production, as well as in atherosclerotic lesion size. The same reference stated that TLR2 genetic polymorphism was linked to increased coronary artery stenosis, while TLR7 & 8 was involved in cardiac inflammation caused by the Coxsackie virus [37].
The liver is the major organ that deals with gut-derived endotoxin, exposed by portal circulation [13, 42]. This continuous exposure would trigger frequent activation of the hepatic innate immune system; which contributes to the induction of inflammation in acute hepatic injuries, which means involvement of TLRs in the induction of inflammation [13]. Pathogenic suppression/& inhibition of TLRs found to mediates chronic hepatic injuries/disorders like hepatitis, fibrosis, alcoholic liver injuries, ischemia/reperfusion injury, and carcinoma [13, 28].
In Paracetamol human hepatotoxicity, endogenous chemical injury derives extracellular matrix (ECM) the ligand that activates TLR4 to release TNF-α, induce inducible nitric oxide synthase (iNOS), peroxynitrite, glutathione depletion, so that will amplify immune response, sequestering leukocytes, increase serum hyaluronic acid, causing steatosis, necrosis, and hepatic congestion [16].
Hepatitis viral nucleic acid & proteins are the ligands detected by TLR3, 7, 8, & 9. Starting with hepatitis B virus (HBV), in vitro activation of TLR1, 2, 3, 4, 5, 6, 7, 8, & 9 result in the release of IFN which inhibit HBV DNA replication and RNA transcription. Whilst HBV itself downregulates the expression of TLR1, 2, 4, & 6, this limits their antiviral effect or even renders them nugatory [28]. This downregulation of TLRs is attributed to the presence of HBV e antigen (HBeAg) during acute infection. About hepatitis C (HCV), its core protein activates TLR 1, 2, 4 & 6, which are supposed to produce antiviral IFNs as well as increased hepatic inflammation. The same effect is presumed by TLR 3 & 4 in HBV is achieved here to produce IFN-β [28].
In alcoholic liver disease (ALD), alcohol mainstay effects are to increase gut mucosal permeability to LPS, modification of gut flora, reducing endotoxin clearance rate, and increasing hepatic endotoxin level [16]. These scenarios lead to higher expression of TLR1, 2, 4, 6 & 9 by both parenchymal and non-parenchymal cells, activating their pathway and release of inflammatory mediators, this process observed in the chronic alcohol experimental model [28, 29]. While a patient with cirrhosis expresses a high level of TNF-α, IL-1β, & IL-6, as well as chronic endotoxemia, recurrent bacterial infection [16]. Finally, the process of hepatic regeneration depends on the interplay between the immune system and non-parenchymal cell, which involves activation of TLRs/MyD88 pathway, here the bulky activation of TLRs, would inversely affect the regeneration process, which indicates that the extent of such activation is essential for hepatic regeneration. TLR2, 4 & 9 reported no important role in liver regeneration process [28, 43].
Both human patients and experimental models of diabetes linked the active TLR to the progression of diabetes complication throughout the activation of NF-κB signalling in adipose tissue MΦ due to high level of plasma FFA associated with obesity & diabetes type 2 (T2DM) [44].
In vivo & in-vitro studies performed by Zhang N. et al. revealed that TLR 2 & 4 activation in insulin target tissues as the liver, adipose tissue & immune cells linked them with insulin resistance. The first suggests that high TLRs loss of function or genetic modification protects against high FFA level resulted from large mass adipose tissue secreting non-esterified free fatty acids & reduction of their clearance/oxidation which disturbs gut permeability to LPs [45].
TLR4 resultant inflammation associated with activation IKK, MAPK, JNK, and p38 pathways would further increase insulin receptor substrate-1 (IRS1) serine phosphorylation thus decrease insulin receptor’s signal transduction [31, 45]. Furthermore, TLR4-MyD88 signalling pathway activation was suggested throughout developmental researches for several anti-hyperlipidemic medications, while TLR1, 2, 3 & 7 were triggering both host immune defence and/autoimmune response that aggravate diabetic state [37].
TLRs expression in renal tube epithelial lining render their activation to be essential in renal vascular remodelling, endothelial dysfunction in multiple renal disorders like acute kidney injury (AKI), solid organ transplant, glomerulonephritis, ischemic/reperfusion injury (I/R injury) & diabetic renal disorders [27, 44]. Experimental streptozocin induced diabetic model revealed podcytopathy & fibrosis regression after TLR4 knocking out, as they are expressed by podocytes & decreased diabetic nephropathy after TLR2 knocking out [46, 47]. TLR4 gene polymorphism was linked to prostate cancer among gene clusters of TLR1, 6 & 10 [37].
TLRs, as the primary receptor for many ligands that trigger innate & adaptive immune response, with complex signaling pathways involving many adaptor molecules & co-receptors seem interesting for therapeutic target development. Synthetic agonist, antagonist and even naturalized antibodies could modify TLRs signaling to make them attractive targets for the management of different inflammatory disease. For example at 2013, Savva and Roger enlisted around 32 clinical trials at different phases for TLRs agonist/antagonist agent for the management of sepsis and infectious disease, these trials include even the antimalarial old agent chloroquine [28, 34].
TLR1/2 heterodimers were found to be increased in patients with atherosclerotic lesions, while administration of TLR1/2 agonist aggravates disease status, also TLR2 inhibition was suggested as diabetes and cardiovascular disorders therapy besides statins & thiazolidinedione by anti-inflammatory action [9]. Pam2/3CSK4 TLR2 ligands covalently linked to CD8+ or B-cell epitopes associated peptides were found to enhance therapeutic response in tumour models, by stimulating TLR2 induced T-cell activation [15]. A 3 component carbohydrate-based cancer vaccine involved TLR2 activator that mediates humoral immune response against tumour-induced glycopeptide antigens by affecting the maturation of cellular component of the innate immune system (DC & natural killer cells), furthermore cancer treatment with chimers of anti-tumour antibodies and small molecule agonist of TLR2 would alleviate disease progression [9].
Since high synovial expression of TLR3 in RA patients was found, one scenario for rheumatoid arthritis and possibly bone malignancy is to inhabit the TLR3 pathway via the RNA synthetic analogue Polyinosine-polycytidylic acid (poly (I:C) that affect monocyte –osteoclast cellular differentiation [9].
Various TLR4 antagonist was developed as a therapeutic agent, starting with the peptide P13- an inhibitor of TIR domain signalling pathway- that was found to ameliorate inflammatory response and improve surviving in a TLR4-mediated hepatic injury of murine model [16]. In addition, Lipid A mimetics E5564 and CRX526 bind to TLR4-MD2 complex showing valuable inhibition of pro-inflammatory cytokine IL-1 and TNF-α production in LPS treated animal models as well as septic shock patients in phase III clinical trial [9, 16, 29]. TLR4 inhibition was suggested as the scenario for treatment of thrombosis, atherosclerosis & vascular restenosis throughout coating TLR4 or MyD88 with inhibitory compound, small molecule antagonist, then by giving viral vectors that express antisense gene to TLR4 RNA [9], and finally TLR4/MD2/anti-Human IgG (Fc specific) (IgG-Fc) fusion protein inhibitor of NF-κB and JNK activation provides interesting biologic therapy for liver fibrosis, alcoholic and non-alcoholic steatohepatitis by decreasing IL-6 and monocyte Chemoattractant Protein-1(MCP-1) production [16].
Another TLR4-synergizer Fc/fusion protein and TL4 ligand α-1 acid glycoprotein were found to inhibit LPS-induced activation of hepatic MΦ by blocking the triggering receptor expressed on myeloid cells-1 (TREM1), and boosting the anti-inflammatory immune response. Other theoretically interesting scenarios involving the I.V administration of monophosphoryl lipid A derivatives as 2 adult HBV vaccine in treating viral hepatitis [13, 15, 16].
One possible scenario for cancer immunotherapy involved TLR5 binding to flagellin that can turn the tolerogenic DCs into active antigen-presenting cells (APC) [9].
Isatoribine, a TLR7 agonist administered I.V was found to decrease viral load with a moderate adverse effect profile in HCV patients. In addition, IGS-9620 that was experimentally assessed on the HBV animal model was found to decrease HBVs antigen (HBsAg) level in serum, HBV viral load as well as IFN-α in dose dependent-manner [15, 29]. Note that some TLR7 targeting therapies were approved by Food and Drug Administration (FDA) like imiquimod, TLR7-immune response modifier that was approved since 1997 for treatment of superficial skin malignant melanoma & genital warts by increasing cellular production of CK like IFN, IL-6 & TNF [9].
Selective TLR9 agonists like 1018 ISS (immunomodulatory sequences) that contain repeated CpG motifs were found to modulate the TLR9 signalling pathway involved in HBV infection and have been tested in phase III clinical trials. Another agonist IMO-2055 was under assessment in 2011 for oncologic disease as well as IMO-2125 which was found to maintain the high level of IFN was under assessment as a possible therapy to HCV patients. The TLR9 intracellular signalling inhibitors ST2825 and RO0884 designed to block IRAK1 &4/MyD88 singling pathway caused inhibition of the NF-κB, IL-1β, and TNF-α activation as well as decreased hepatic IL-6 secretion [9, 15, 29].
Medical and pharmacological development is focusing on the molecular level, in all aspects including analytical, physiological, pharmacological and even genetic aspects. Understanding immune response is thus important subject, furthermore, the target receptors which damage signals bind to, their signaling pathways end products will tell what possible immune response happened to human body. Toll-like receptors are those targets, the family of integral transmembrane glycoprotein expressed intracellularly or at cellular surface, considered main component and link between innate and adaptive immune response, which can induce signaling pathways involving four main adaptor molecules that initiate divaricated steps ending with inflammatory cytokines. These pathways could be involved in any inflammatory process/disorders and thus seems interesting targets for pharmacological intervention; all these steps bring us back to the bullet that explodes all these events in the body, the immune system.
The author declares no conflict of interest.
After precious Thanks to Almighty and Merciful GOD, I would like to express my thanks and gratitude to Professor G. H. Majeed who made it possible to me to accomplish this situation and reach you, my readers. Also to the magnificent group who introduced me to the world of toll-like receptors: professor Dr. Abduladheem Y. Abbood Al-Barrak, professor Dr. Bassim I. Mohammad, Dr. Samer Fadhel Hassan, Dr. Asma A. Swadi, and Dr. Huda J. Merza, and sure my own family.
Acute kidney injury Alcoholic liver disease Acute lung injury Angiotensin II Adaptor protein-1 Antigen-presenting cell Acute respiratory distress syndrome B cell lymphoma 2 Chemokine Cluster differential 14 Pro-inflammatory cytokines Cytosine phosphate guanine Damage-associated molecular pattern Dendritic cell Extracellular domain Extracellular matrix Free fatty acids Free radicals HBV e antigen HBV s antigen Hypoxia-inducible factor-1 Heat shock protein Ischemic/reperfusion injury Cytoplasmic domain Type-I interferon Anti-Human IgG (Fc specific) Inhibitor of kappa-B (IκB) kinase Interleukin Inducible nitric oxide synthase Inositol triphosphate-3 IL-1 receptor-associated kinase Interferon regulatory factor Inhibitor of kappa-B Jun (N)terminal kinase Lipopolysaccharides Leucine-rich repeat Lipoteichoic acid Mitogen-activated protein kinase Extracellular signal-regulated kinases Mast cell Monocyte Chemoattractant Protein-1 Lymphocyte antigen 96 Myocardial infarction Messenger ribonucleic acid Myeloid differential88 Macrophage nicotine amide adenine dinucleotide phosphate nucleotide oligomerization domain (NOD)-like receptors Nitric oxide nucleotide oligomerization domain NADPH oxidase Pam3CysSerLys4 Pathogen-associated molecular patterns Plasmatoid dendritic cells Peptidoglycan Phosphoinositide-3 Polyinosine-polycytidylic acid Pattern recognition receptors retinoic acid-inducible gene I retinoic acid-inducible gene I (RIG-I)-like receptors Reactive oxygen species Diabetes type 2 Transforming growth factor (TGF)-β-activated kinase Serine/threonine binding kinase Transcription factors Transforming growth factor Toll/IL-receptor TIR domain-containing adaptor protein/MyD88 adaptor like Toll-like receptors Tumour necrosis factor-alpha Toll interacting protein TNF receptor-associated factor-6 TRIF related adaptor molecule Regulatory T cells Triggering receptor expressed on myeloid cells-1 TIR domain-containing adaptor protein inducing interferon-β
YouTube video: [3] Armando Hasudungan, Immunology-Toll Like Receptors Overview [Internet. YouTube]. 2014. Available from: https://youtu.be/8mEnyBdsrr8
YouTube video: [18] Armando Hasudungan, Immunology - Toll Like Receptors Overview [Internet YouTube]. 2014. Available from: https://youtu.be/8mEnyBdsrr8
Authors are listed below with their open access chapters linked via author name:
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\\n\\n\\n\\n\\n\\n\\n\\n\\n\\nJocelyn Chanussot (chapter to be published soon...)
\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\nYuekun Lai
\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\nPrevious years (alphabetically by surname)
\\n\\nAbdul Latif Ahmad 2016-18
\\n\\nKhalil Amine 2017, 2018
\\n\\nEwan Birney 2015-18
\\n\\nFrede Blaabjerg 2015-18
\\n\\nGang Chen 2016-18
\\n\\nJunhong Chen 2017, 2018
\\n\\nZhigang Chen 2016, 2018
\\n\\nMyung-Haing Cho 2016, 2018
\\n\\nMark Connors 2015-18
\\n\\nCyrus Cooper 2017, 2018
\\n\\nLiming Dai 2015-18
\\n\\nWeihua Deng 2017, 2018
\\n\\nVincenzo Fogliano 2017, 2018
\\n\\nRon de Graaf 2014-18
\\n\\nHarald Haas 2017, 2018
\\n\\nFrancisco Herrera 2017, 2018
\\n\\nJaakko Kangasjärvi 2015-18
\\n\\nHamid Reza Karimi 2016-18
\\n\\nJunji Kido 2014-18
\\n\\nJose Luiszamorano 2015-18
\\n\\nYiqi Luo 2016-18
\\n\\nJoachim Maier 2014-18
\\n\\nAndrea Natale 2017, 2018
\\n\\nAlberto Mantovani 2014-18
\\n\\nMarjan Mernik 2017, 2018
\\n\\nSandra Orchard 2014, 2016-18
\\n\\nMohamed Oukka 2016-18
\\n\\nBiswajeet Pradhan 2016-18
\\n\\nDirk Raes 2017, 2018
\\n\\nUlrike Ravens-Sieberer 2016-18
\\n\\nYexiang Tong 2017, 2018
\\n\\nJim Van Os 2015-18
\\n\\nLong Wang 2017, 2018
\\n\\nFei Wei 2016-18
\\n\\nIoannis Xenarios 2017, 2018
\\n\\nQi Xie 2016-18
\\n\\nXin-She Yang 2017, 2018
\\n\\nYulong Yin 2015, 2017, 2018
\\n"}]'},components:[{type:"htmlEditorComponent",content:'New for 2018 (alphabetically by surname).
\n\n\n\n\n\n\n\n\n\nJocelyn Chanussot (chapter to be published soon...)
\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nYuekun Lai
\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nPrevious years (alphabetically by surname)
\n\nAbdul Latif Ahmad 2016-18
\n\nKhalil Amine 2017, 2018
\n\nEwan Birney 2015-18
\n\nFrede Blaabjerg 2015-18
\n\nGang Chen 2016-18
\n\nJunhong Chen 2017, 2018
\n\nZhigang Chen 2016, 2018
\n\nMyung-Haing Cho 2016, 2018
\n\nMark Connors 2015-18
\n\nCyrus Cooper 2017, 2018
\n\nLiming Dai 2015-18
\n\nWeihua Deng 2017, 2018
\n\nVincenzo Fogliano 2017, 2018
\n\nRon de Graaf 2014-18
\n\nHarald Haas 2017, 2018
\n\nFrancisco Herrera 2017, 2018
\n\nJaakko Kangasjärvi 2015-18
\n\nHamid Reza Karimi 2016-18
\n\nJunji Kido 2014-18
\n\nJose Luiszamorano 2015-18
\n\nYiqi Luo 2016-18
\n\nJoachim Maier 2014-18
\n\nAndrea Natale 2017, 2018
\n\nAlberto Mantovani 2014-18
\n\nMarjan Mernik 2017, 2018
\n\nSandra Orchard 2014, 2016-18
\n\nMohamed Oukka 2016-18
\n\nBiswajeet Pradhan 2016-18
\n\nDirk Raes 2017, 2018
\n\nUlrike Ravens-Sieberer 2016-18
\n\nYexiang Tong 2017, 2018
\n\nJim Van Os 2015-18
\n\nLong Wang 2017, 2018
\n\nFei Wei 2016-18
\n\nIoannis Xenarios 2017, 2018
\n\nQi Xie 2016-18
\n\nXin-She Yang 2017, 2018
\n\nYulong Yin 2015, 2017, 2018
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Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6978",title:"Antimicrobial Resistance",subtitle:"A Global Threat",isOpenForSubmission:!1,hash:"949e88946357845e5843b4d7fbc1701f",slug:"antimicrobial-resistance-a-global-threat",bookSignature:"Yashwant Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/6978.jpg",editedByType:"Edited by",editors:[{id:"79718",title:"Dr.",name:"Yashwant",middleName:null,surname:"Kumar",slug:"yashwant-kumar",fullName:"Yashwant Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8427",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",subtitle:null,isOpenForSubmission:!1,hash:"0fdedc9bf6c23241235a0ae011c0304c",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",bookSignature:"Sahra Kırmusaoğlu",coverURL:"https://cdn.intechopen.com/books/images_new/8427.jpg",editedByType:"Edited by",editors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4648",title:"Concepts, Compounds and the Alternatives of Antibacterials",subtitle:null,isOpenForSubmission:!1,hash:"ba284c040146d00fdd709cabc4c8cb5a",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",bookSignature:"Varaprasad Bobbarala",coverURL:"https://cdn.intechopen.com/books/images_new/4648.jpg",editedByType:"Edited by",editors:[{id:"90574",title:"Dr.",name:"Varaprasad",middleName:null,surname:"Bobbarala",slug:"varaprasad-bobbarala",fullName:"Varaprasad Bobbarala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4759",title:"Antimicrobial Resistance",subtitle:"An Open Challenge",isOpenForSubmission:!1,hash:"04be7bb9b8da174cdb838a38c75236b4",slug:"antimicrobial-resistance-an-open-challenge",bookSignature:"Maria Cristina Ossiprandi",coverURL:"https://cdn.intechopen.com/books/images_new/4759.jpg",editedByType:"Edited by",editors:[{id:"80691",title:"Prof.",name:"Maria Cristina",middleName:null,surname:"Ossiprandi",slug:"maria-cristina-ossiprandi",fullName:"Maria Cristina Ossiprandi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:6,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"62553",doi:"10.5772/intechopen.79371",title:"Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance",slug:"antibiotic-use-in-poultry-production-and-its-effects-on-bacterial-resistance",totalDownloads:7333,totalCrossrefCites:43,totalDimensionsCites:92,abstract:"A surge in the development and spread of antibiotic resistance has become a major cause for concern. Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"49246",doi:"10.5772/61300",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4727,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]},{id:"70919",doi:"10.5772/intechopen.90891",title:"Antimicrobial Effect of Titanium Dioxide Nanoparticles",slug:"antimicrobial-effect-of-titanium-dioxide-nanoparticles",totalDownloads:1817,totalCrossrefCites:21,totalDimensionsCites:47,abstract:"The widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains, and therefore a current concern for food safety and human health. The interest for new antimicrobial substances has been focused toward metal oxide nanoparticles. Specifically, titanium dioxide (TiO2) has been considered as an attractive antimicrobial compound due to its photocatalytic nature and because it is a chemically stable, non-toxic, inexpensive, and Generally Recognized as Safe (GRAS) substance. Several studies have revealed this metal oxide demonstrates excellent antifungal and antibacterial properties against a broad range of both Gram-positive and Gram-negative bacteria. These properties were significantly improved by titanium dioxide nanoparticles (TiO2 NPs) synthesis. In this chapter, latest developments on routes of synthesis of TiO2 NPs and antimicrobial activity of these nanostructures are presented. Furthermore, TiO2 NPs favor the inactivation of microorganisms due to their strong oxidizing power by free radical generation, such as hydroxyl and superoxide anion radicals, showing reductions growth against several microorganisms, such as Escherichia coli and Staphylococcus aureus. Understanding the main mechanisms of antimicrobial action of these nanoparticles was the second main purpose of this chapter.",book:{id:"9521",slug:"antimicrobial-resistance-a-one-health-perspective",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A One Health Perspective"},signatures:"Carol López de Dicastillo, Matias Guerrero Correa, Fernanda B. Martínez, Camilo Streitt and Maria José Galotto",authors:[{id:"244902",title:"Dr.",name:"Carol",middleName:null,surname:"Lopez De Dicastillo",slug:"carol-lopez-de-dicastillo",fullName:"Carol Lopez De Dicastillo"},{id:"315494",title:"Mr.",name:"Matias",middleName:null,surname:"Guerrero Correa",slug:"matias-guerrero-correa",fullName:"Matias Guerrero Correa"},{id:"315495",title:"Ms.",name:"Fernanda",middleName:null,surname:"B. Martínez",slug:"fernanda-b.-martinez",fullName:"Fernanda B. Martínez"},{id:"315496",title:"Mr.",name:"Camilo",middleName:null,surname:"Zuñiga",slug:"camilo-zuniga",fullName:"Camilo Zuñiga"},{id:"315497",title:"Dr.",name:"Maria José",middleName:null,surname:"Galotto",slug:"maria-jose-galotto",fullName:"Maria José Galotto"}]},{id:"65613",doi:"10.5772/intechopen.84411",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9283,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"63397",doi:"10.5772/intechopen.80624",title:"Antibiotic Resistance in Lactic Acid Bacteria",slug:"antibiotic-resistance-in-lactic-acid-bacteria",totalDownloads:2486,totalCrossrefCites:12,totalDimensionsCites:21,abstract:"Most starter cultures belong to the lactic acid bacteria group (LAB) and recognized as safe by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, LAB may act as intrinsic or extrinsic reservoirs for antibiotic resistance (AR) genes. This fact may not constitute a safety concern itself, as the resistance gene transfer is vertical. Nevertheless, external genetic elements may induce changes that favor the horizontal transfer transmission of resistance from pathogens as well as from the human intestinal microbiota, which represents a severe safety issue. Some genus of AR LAB includes Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Streptococcus isolated from fermented meat and milk products. Currently, the WHO recommends that LAB used in the food industry should be free of resistance. Therefore, the objective of this chapter is to present an overview of the LAB antibiotic resistance and some methods to determine the same.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Yenizey M. Álvarez-Cisneros and Edith Ponce-Alquicira",authors:[{id:"256345",title:"Dr.",name:"Yenizey Merit",middleName:null,surname:"Alvarez Cisneros",slug:"yenizey-merit-alvarez-cisneros",fullName:"Yenizey Merit Alvarez Cisneros"},{id:"256347",title:"Dr.",name:"Edith",middleName:null,surname:"Ponce-Alquicira",slug:"edith-ponce-alquicira",fullName:"Edith Ponce-Alquicira"}]}],mostDownloadedChaptersLast30Days:[{id:"65613",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9277,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"62553",title:"Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance",slug:"antibiotic-use-in-poultry-production-and-its-effects-on-bacterial-resistance",totalDownloads:7327,totalCrossrefCites:43,totalDimensionsCites:92,abstract:"A surge in the development and spread of antibiotic resistance has become a major cause for concern. Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"65914",title:"Introductory Chapter: The Action Mechanisms of Antibiotics and Antibiotic Resistance",slug:"introductory-chapter-the-action-mechanisms-of-antibiotics-and-antibiotic-resistance",totalDownloads:4428,totalCrossrefCites:6,totalDimensionsCites:10,abstract:null,book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu, Nesrin Gareayaghi and Bekir S. Kocazeybek",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"},{id:"248288",title:"Prof.",name:"Bekir",middleName:null,surname:"Kocazeybek",slug:"bekir-kocazeybek",fullName:"Bekir Kocazeybek"},{id:"406463",title:"Dr.",name:"Nesrin",middleName:null,surname:"Gareayaghi",slug:"nesrin-gareayaghi",fullName:"Nesrin Gareayaghi"}]},{id:"63397",title:"Antibiotic Resistance in Lactic Acid Bacteria",slug:"antibiotic-resistance-in-lactic-acid-bacteria",totalDownloads:2486,totalCrossrefCites:12,totalDimensionsCites:21,abstract:"Most starter cultures belong to the lactic acid bacteria group (LAB) and recognized as safe by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, LAB may act as intrinsic or extrinsic reservoirs for antibiotic resistance (AR) genes. This fact may not constitute a safety concern itself, as the resistance gene transfer is vertical. Nevertheless, external genetic elements may induce changes that favor the horizontal transfer transmission of resistance from pathogens as well as from the human intestinal microbiota, which represents a severe safety issue. Some genus of AR LAB includes Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Streptococcus isolated from fermented meat and milk products. Currently, the WHO recommends that LAB used in the food industry should be free of resistance. Therefore, the objective of this chapter is to present an overview of the LAB antibiotic resistance and some methods to determine the same.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Yenizey M. Álvarez-Cisneros and Edith Ponce-Alquicira",authors:[{id:"256345",title:"Dr.",name:"Yenizey Merit",middleName:null,surname:"Alvarez Cisneros",slug:"yenizey-merit-alvarez-cisneros",fullName:"Yenizey Merit Alvarez Cisneros"},{id:"256347",title:"Dr.",name:"Edith",middleName:null,surname:"Ponce-Alquicira",slug:"edith-ponce-alquicira",fullName:"Edith Ponce-Alquicira"}]},{id:"49246",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4726,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]}],onlineFirstChaptersFilter:{topicId:"897",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81704",title:"Quorum Sensing Inhibition Based Drugs to Conquer Antimicrobial Resistance",slug:"quorum-sensing-inhibition-based-drugs-to-conquer-antimicrobial-resistance",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104125",abstract:"Quorum sensing is the cell to cell communication mechanism in microorganism through signalling molecules. Regulation of virulence factor, sporulation, proteolytic enzymes production, biofilm formation, auto-inducers, cell population density are key physiological process mediated through quorum-sensing (QS) signalling. Elevation of innate immune system and antibiotic tolerance of pathogens is highly increased with perspective of quorum-sensing (QS) activity. Development of novel drugs is highly attractive scenario against cell-cell communication of microbes. Design of synthetic drugs and natural compounds against QS signal molecules is vital combat system to attenuate microbial pathogenicity. Quorum sensing inhibitors (QSIs), quorum quenchers (QQs), efflux pump inhibitors (EPIs) act against multi-drug resistance strains (MDR) and other pathogenic microbes through regulation of auto-inducers and signal molecule with perceptive to growth arrest both in-vitro and in-vivo. QQs, QSIs and EPIs compounds has been validated with various animal models for high selection pressure on therapeutics arsenal against microbe’s growth inhibition. Promising QSI are phytochemicals and secondary metabolites includes polyacetylenes, alkaloids, polyphenols, terpenoids, quinones.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Kothandapani Sundar, Ramachandira Prabu and Gopal Jayalakshmi"},{id:"82372",title:"Unlocking the Potential of Ghost Probiotics in Combating Antimicrobial Resistance",slug:"unlocking-the-potential-of-ghost-probiotics-in-combating-antimicrobial-resistance",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104126",abstract:"Antimicrobial resistance is a global concern that requires immediate attention. Major causes of development of antimicrobial resistance in microbial cells are overuse of antimicrobials along the food chain especially in livestock, in preventing infections as well as misuse of antimicrobials by patients. Probiotics could be a viable alternative to antibiotics in the fight against antimicrobial resistance. Probiotic strains can act as a complement to antimicrobial therapy, improving antimicrobial function and enhancing immunity. However, there are safety concerns regarding the extensive use of live microbial cells especially in immunocompromised individuals; these include microbial translocation, inhibition of other beneficial microorganisms and development of antimicrobial resistance, among other concerns. Inevitably, ghost probiotics have become the favored alternative as they eliminate the safety and shelf-life problems associated with use of probiotics. Ghost probiotics are non-viable microbial cells (intact or broken) or metabolic products from microorganisms, which when administered in adequate amounts have biologic activity in the host and confer health benefits. Ghost probiotics exert biological effects similar to probiotics. However, the major drawback of using ghost probiotics is that the mechanism of action of these is currently unknown, hence more research is required and regulatory instruments are needed to assure the safety of consumers.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Abigarl Ndudzo, Sakhile Ndlovu, Nesisa Nyathi and Angela Sibanda Makuvise"},{id:"82178",title:"Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role of One Health",slug:"managing-antimicrobial-resistance-beyond-the-hospital-antimicrobial-stewardship-the-role-of-one-heal",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.104170",abstract:"Infections caused by micro-organisms affect the health of people and animals, causing morbidity and mortality, with Asia and Africa as the epicenters. Some of the infectious diseases are emerging and re-emerging in nature. Examples include viral hepatitis, Lassa fever, Ebola, yellow fever, tuberculosis, covid-19, measles, and malaria, among others. Antimicrobials have been playing an important role in the treatment of infections by these microbes. However, there has been a development of resistance to these antimicrobials as a result of many drivers. This write-up used secondary data to explore the management of antimicrobial resistance (AMR) beyond the hospital antimicrobial resistance steward using the one health concept. The findings showed AMR to be a transboundary, multifaceted ecosystem problem affecting both the developed and developing countries. It is also one of the top ten global public health threats facing mankind. Globally, AMR will cost over US$100 trillion in output loss by 2050, about 700,000 deaths a year, and 4,150,000 deaths in Africa by 2050. About 2.4 million people could die in high-income countries between 2015 and 2050 without a sustained effort to contain AMR. The drivers of AMR are beyond the hospital and hospital AMR stewardship. Therefore, the need for one health concept to manage it.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Istifanus Anekoson Joshua, Mathew Bobai and Clement Sokfa Woje"},{id:"81918",title:"Machine Learning for Antimicrobial Resistance Research and Drug Development",slug:"machine-learning-for-antimicrobial-resistance-research-and-drug-development",totalDownloads:53,totalDimensionsCites:0,doi:"10.5772/intechopen.104841",abstract:"Machine learning is a subfield of artificial intelligence which combines sophisticated algorithms and data to develop predictive models with minimal human interference. This chapter focuses on research that trains machine learning models to study antimicrobial resistance and to discover antimicrobial drugs. An emphasis is placed on applying machine learning models to detect drug resistance among bacterial and fungal pathogens. The role of machine learning in antibacterial and antifungal drug discovery and design is explored. Finally, the challenges and prospects of applying machine learning to advance basic research on and treatment of antimicrobial resistance are discussed. Overall, machine learning promises to advance antimicrobial resistance research and to facilitate the development of antibacterial and antifungal drugs.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Shamanth A. Shankarnarayan, Joshua D. Guthrie and Daniel A. Charlebois"},{id:"81891",title:"Alternatives to Antibiotics in Semen Extenders Used in Artificial Insemination",slug:"alternatives-to-antibiotics-in-semen-extenders-used-in-artificial-insemination",totalDownloads:29,totalDimensionsCites:0,doi:"10.5772/intechopen.104226",abstract:"Antimicrobial resistance is a serious global threat requiring a widespread response. Both veterinarians and medical doctors should restrict antibiotic usage to therapeutic use only, after determining the sensitivity of the causal organism. However, the addition of antibiotics to semen extenders for animal artificial insemination represents a hidden, non-therapeutic use of antimicrobial substances. Artificial insemination for livestock breeding is a huge global enterprise with hundreds of million sperm doses prepared annually. However, reporting of antimicrobial resistance in semen is increasing. This review discusses the consequences of bacteria in semen samples, as well as the effect of antimicrobial substances in semen extenders on bacteria in the environment and even on personnel. Alternatives to antibiotics have been reported in the scientific literature and are reviewed here. The most promising of these, removal of the majority of bacteria by colloid centrifugation, is considered in detail, especially results from an artificial insemination study in pigs. In conclusion, colloid centrifugation is a practical method of physically removing bacteria from semen, which does not induce antibiotic resistance. Sperm quality in stored semen samples may be improved at the same time.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Jane M. Morrell, Pongpreecha Malaluang, Aleksandar Cojkic and Ingrid Hansson"},{id:"81699",title:"Efflux Pumps among Urinary E. coli and K. pneumoniae Local Isolates in Hilla City, Iraq",slug:"efflux-pumps-among-urinary-e-coli-and-k-pneumoniae-local-isolates-in-hilla-city-iraq",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104408",abstract:"Urinary tract infections (UTI) are the most common bacterial infections affecting humans. Escherichia coli and Klebsiella pneumoniae were common enterobacteria engaged with community-acquired UTIs. Efflux pumps were vital resistance mechanisms for antibiotics, especially among enterobacteria. Overexpression of an efflux system, which results in a decrease in antibiotic accumulation, is an effective mechanism for drug resistance. The ATP-binding cassette (ABC) transporters, small multidrug resistance (SMR), and multidrug and toxic compound extrusion (MATE) families, the major facilitator superfamily (MFS), and the resistance-nodulation- cell division (RND) family are the five superfamilies of efflux systems linked to drug resistance. This chapter highlights the results of studying the prevalence of efflux pump genes among local isolates of E. coli and K. pneumoniae in Hilla City, Iraq. class RND AcrAB-TolC, AcrAD-TolC, and AcrFE-TolC genes detected by conventional PCR of E. coli and K. pneumoniae respectively. The result revealed approximately all studied efflux transporter were found in both E. coli and K. pneumoniae in different percentages. Biofilm formation were observed in 50(100%) of K. pneumoniae and 49(98%) of E. coli isolates were biofilm former and follow: 30(60%), 20(40%) were weak, 12(24%), 22(44%) were moderate and 7(14%) and 8(16%) were Strong biofilm former for E. coli and K. pneumoniae, respectively.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Hussein Al-Dahmoshi, Sahar A. Ali and Noor Al-Khafaji"}],onlineFirstChaptersTotal:13},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"July 20th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:14,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"306970",title:"Mr.",name:"Amin",middleName:null,surname:"Tamadon",slug:"amin-tamadon",fullName:"Amin Tamadon",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002oHR5wQAG/Profile_Picture_1623910304139",institutionString:null,institution:{name:"Bushehr University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",institutionURL:null,country:{name:"Spain"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",institutionString:null,institution:{name:"Miguel Hernandez University",institutionURL:null,country:{name:"Spain"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",institutionString:null,institution:{name:"Alexandria University",institutionURL:null,country:{name:"Egypt"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",institutionString:"Kafkas University",institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}}]},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević",profilePictureURL:"https://mts.intechopen.com/storage/users/186048/images/5818_n.jpg",institutionString:null,institution:{name:"University of Osijek",institutionURL:null,country:{name:"Croatia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria",profilePictureURL:"https://mts.intechopen.com/storage/users/79615/images/system/79615.png",institutionString:null,institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}},{id:"84459",title:"Prof.",name:"Valerie",middleName:null,surname:"Chappe",slug:"valerie-chappe",fullName:"Valerie Chappe",profilePictureURL:"https://mts.intechopen.com/storage/users/84459/images/system/84459.jpg",institutionString:null,institution:{name:"Dalhousie University",institutionURL:null,country:{name:"Canada"}}}]},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"213786",title:"Dr.",name:"Henrique P.",middleName:null,surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. Neiva",profilePictureURL:"https://mts.intechopen.com/storage/users/213786/images/system/213786.png",institutionString:null,institution:{name:"University of Beira Interior",institutionURL:null,country:{name:"Portugal"}}},{id:"39275",title:"Prof.",name:"Herbert Ryan",middleName:null,surname:"Marini",slug:"herbert-ryan-marini",fullName:"Herbert Ryan Marini",profilePictureURL:"https://mts.intechopen.com/storage/users/39275/images/9459_n.jpg",institutionString:null,institution:{name:"University of Messina",institutionURL:null,country:{name:"Italy"}}},{id:"319576",title:"Prof.",name:"Nikolay",middleName:null,surname:"Boyadjiev",slug:"nikolay-boyadjiev",fullName:"Nikolay Boyadjiev",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v4b3cQAA/Profile_Picture_2022-06-07T08:30:58.jpeg",institutionString:null,institution:{name:"Medical University Plovdiv",institutionURL:null,country:{name:"Bulgaria"}}},{id:"196218",title:"Dr.",name:"Pasquale",middleName:null,surname:"Cianci",slug:"pasquale-cianci",fullName:"Pasquale Cianci",profilePictureURL:"https://mts.intechopen.com/storage/users/196218/images/system/196218.png",institutionString:null,institution:{name:"University of Foggia",institutionURL:null,country:{name:"Italy"}}}]},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"313856",title:"Dr.",name:"Christophe",middleName:"F.E.",surname:"Hano",slug:"christophe-hano",fullName:"Christophe Hano",profilePictureURL:"https://mts.intechopen.com/storage/users/313856/images/system/313856.png",institutionString:"University of Orléans",institution:{name:"University of Orléans",institutionURL:null,country:{name:"France"}}},{id:"33993",title:"Dr.",name:"Jose Carlos",middleName:null,surname:"Jimenez-Lopez",slug:"jose-carlos-jimenez-lopez",fullName:"Jose Carlos Jimenez-Lopez",profilePictureURL:"https://mts.intechopen.com/storage/users/33993/images/system/33993.jpg",institutionString:"Spanish National Research Council",institution:{name:"Spanish National Research Council",institutionURL:null,country:{name:"Spain"}}},{id:"191770",title:"Dr.",name:"Mohamed A.",middleName:null,surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. El-Esawi",profilePictureURL:"https://mts.intechopen.com/storage/users/191770/images/system/191770.jpeg",institutionString:null,institution:{name:"Tanta University",institutionURL:null,country:{name:"Egypt"}}},{id:"247858",title:"Dr.",name:"Saddam",middleName:null,surname:"Hussain",slug:"saddam-hussain",fullName:"Saddam Hussain",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSF2aQAG/Profile_Picture_1625658281836",institutionString:null,institution:{name:"University of Agriculture Faisalabad",institutionURL:null,country:{name:"Pakistan"}}}]}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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