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Tolerance to self-components develops both during embryonic development (i.e., central tolerance, which occurs in the primary lymphoid organs, along with the process of lymphocyte differentiation), and after birth (i.e., peripheral tolerance) [1].
Currently, the microbiota is considered an anatomically integrated meta-organ that performs functions through which it interferes with the host’s physiology [2]. Thus, microbiota eubiosis is a major parameter of physiological homeostasis. Human microbiota establishes three types of relationships with the host—symbiotic, commensal, and pathobiontic, respectively [3]. The terms “microbiota” and “microbiome” are equivalent, but not identical. The first refers to the population of microorganisms residing on the mucous membranes of the digestive, urogenital and respiratory tract, as well as on the skin, and the second designates the collective genome of the microbiota, called the metagenome [4]. The community microbiome was evaluated at 3.3 million redundant bacterial genes, about 150 times larger than the human gene complex [5]. The gut microbiota is influenced by various conditions, such as diet, health, mental stress, gender, or exercise, and conversely, it influences all body metabolism, immune reactivity, and behavior [6]. The microbiota contributes to the peripheral tolerance of the immune system toward autoantigens, with the retention of the immune reactivity against all antigens that do not cross-react with the tolerated antigen. Interruption of tolerance initiates an immune response to self-antigens characterized by the production of autoantibodies or autoreactive lymphocytes, which trigger an autoimmune conflict [7]. The purpose of this chapter is to highlight the role of the normal microbiota in the state of immune tolerance and to investigate the correlations of dysbiosis with endocrine AIDS.
The microbiota of the digestive tract consists of about 3 × 1013 to 40 × 1013 (3–40 trillion) bacterial cells, counting at least 10 times more than their host cells. The groups of
The microbiota is considered a virtual organ, whose functions must be integrated into general physiology. The host-microbiota interaction is primarily a symbiotic relationship, in which the host organism provides the ecological niche and nutrients for microbiota survival. The microbiota carries out fermentative and biosynthetic metabolic activities, thereby influencing systemic physiology [12]. The metabolism of the microbiota functions as a bridge between the diet with the human body. The intestinal microbiota increases the energy efficiency of the diet by fermenting the fibrous components, providing essential metabolites for organ systems, especially short-chain fatty acids (SCFA), such as acetic, propionic, and butyric acid. A proportion of 50% of the energy needs of epithelial cells is provided by SCFA [13, 14]. The modern diet is 7–10 times poorer in the fibrous component, compared to the traditional Mediterranean one. Microbiota synthesizes vitamin K and B, synthesizes amines through which it modifies endocrine function, stimulates the inflammatory process, has a protective role against the invasion of enteric pathogens (
From an immunological perspective, the mucous membranes which cover a total area of about 400 m2, represent both an anatomical and functional entity, because they are populated by a large number of immune cells.
The intestinal microbiota, epithelium and digestive, respiratory, genital, urinary mucosa-associated immune system form a functional triad whose components influence each other close interactions, with a rapid dynamic of change, induced by population changes of the microbiota, due to diet variation and/or administration of antibiotics. The modification of the functional parameters of a component of the triad has major influences on the physiology of the whole organism. The microbiota interacts directly with the epithelium of the adjacent mucosa and influences its permeability, and both local and systemic inflammatory responses [10] The interaction of the microbiota with the mucosal immune system (gut-associated lymphoid tissue—GALT) induces the synthesis of a wide set of cytokines, with local regulatory action of intestinal physiology [20, 21].
The microbiota has an essential role in the functional modulation (education), first of all of the GALT structures. Germ-free and gnotobiotic animal studies have made a decisive contribution to understanding the functional relationships of the microbiota-epithelium-immune system triad and provided new evidence for the role of the intestinal microbiota as a whole, but also of different groups of bacteria in the functional development and maturation of the systemic immune system, especially GALT. Germ-free mice have structural and functional defects of the immune system—decreased TCD4 lymphocyte count and Th-2 predominance in the spleen, altered Th-17 and T-reg differentiation in the lamina propria, and restoration of deficiencies after colonization with
M cells that cover the subepithelial immune structures engulf the luminal antigens, through the mechanism of pinocytosis and transfer them unaffected to the immune structures in the underlying follicles (i.e., macrophages, dendritic cells, T and B lymphocytes). Macrophages and dendritic cells respond to microbiota antigens in a nonspecific manner by TLR recognition followed by cytokines release (i.e., IFNα, IL-18, and IL-22), which stimulate the epithelial cells to synthesize antimicrobial peptides.
The microbiota, through the composition of bacterial phyla, has a major influence on the development of T lymphocyte subpopulations and in maintaining the numerical balance of Th-2/Th-1 lymphocyte populations in lymphoid organs. The differentiation of T lymphocyte sets is influenced by the antigenic specificity of the dominant bacterial population and its metabolic properties—(i) some bacteria stimulate the predominant differentiation of proinflammatory TCD4 lymphocytes that synthesize IFNγ and IL-17A [25]; and (ii) others stimulate the differentiation of regulatory CD25+ and Foxp3+ TCD4 lymphocytes (T-reg), the essential mediator of immune tolerance by decreasing Th-17 lymphocytes [26, 27]. The direct relationship between the concentration of butyric acid and the number of T-reg lymphocytes is well known. SCFA, particularly butyric acid harbor important roles, that is, stimulate gene transcription for mucin synthesis, strengthen the intestinal barrier and render it impermeable to toxins and bacterial cell translocation, thus preventing chronic systemic inflammation, inhibiting the synthesis of pro-inflammatory interleukins (IL) (TNFα and IL-6) induced by LPS and regulate the innate and adaptive immunity [13, 14]. Th-17 lymphocytes play an essential role in anti-bacterial and anti-fungal defense, but at the same time have an important role in the initiation of inflammatory diseases, through the synthesis of pro-inflammatory IL-17 and IL-22 and the recruitment of neutrophils. In germ-free animals, the lamina propria is populated by a very small number of Th-17 lymphocytes [9]. Th-17 lymphocytes also decrease after antibiotic treatment [27]. The group of
The microbiota has also a profound influence on the development of B lymphocytes—it stimulates the synthesis of antibodies, especially of IgA type, targeted against thymus-dependent (Td), and thymus-independent (Ti) antigens. The
In germ-free animals, GALT structures play a key role in inducing immune tolerance against auto-antigens from the intestinal mucosa, are less developed and indicators of immune response activation are lacking. In these animals, the number of TCD4 lymphocytes and IgA-secreting plasma cells decreases in Peyer’s patches, while in the spleen and lymph nodes, the number of B lymphocytes and germinal centers decreases.
In conclusion, the development, maturation, and function of the immune system are closely associated with the level of exposure to microbial antigens during early life, and as an opposite, insufficient exposure to various antigens increases the risk of autoimmune disorders occurrence [29].
Despite its much-diversified antigen panel, the microbiota is tolerated by the immune system. Central tolerance is induced during fetal life, as immature lymphocytes are exposed to various antigenic peptides, and is essentially dependent on the specific process of antigenic peptide selection and presentation in association with the Human Leucocytes Antigen/ Major Histocompatibility Complex (HLA/MHC) molecules [30]. The occurrence of peripheral tolerance breaks results from a functional adaptation of the immune system to specific antigenic peptides that have not (sufficiently) been exposed to lymphocytes in the bone marrow or thymus during embryonic development. It is now considered that the T lymphocyte antigen receptor (TCR) is the major mediator of immune tolerance. That is why, from an evolutionary perspective, TCR recognizes both the genetic and microbial self [31].
The immune tolerance to commensal intestinal microbiota is peripheral and results from both an immediate neonate colonization of the digestive tract and a progressive co-evolution in which the interactions of gut-associated lymphoid tissue (i.e., GALT) with bacterial antigens have been modulating innate and adaptive primarily local immune reactivity. Commensal antigens, on contact with the intestinal mucosa, induce the state of tolerance, in which dendritic cells play an essential role, while the effectors are the epithelial cells with their covering molecular complex (i.e., antimicrobial peptides, mucin layer, surface immunoglobulin A—sIgA) [32]. Bacterial cells or their components (i.e., lipopolysaccharides, polysaccharides, peptidoglycans, teichoic acids, and DNA) that cross the intestinal barrier and reach the internal environment, activate the immune response [33].
Interruption of immune tolerance to microbiota antigens is determined by several factors—genetic factors, the host’s immune system, disturbance of the diversity, and physiology of the microbiota—as triggering events [34].
Mechanisms that modulate immune tolerance loss to the intestinal microbiota include: (i) abnormal translocation of bacteria in the internal environment due to permeability of the intestinal barrier, (ii) antigenic similarity of some bacterial peptides with epithelial molecules. Immune cells are activated by bacterial peptides and become autoreactive; and (iii) disorder of local and systemic immunity under the stimulating action of some bacterial derivatives (nucleic acids, polysaccharides, metabolites, and toxins). Aberrant activation of the immune system leads to the excessive synthesis of proinflammatory IL (IFN type I, IL-12, IL-23) and a decreased rate of synthesis of anti-inflammatory cytokines (IL-10, TGF-β—transforming growth factor) (Figure 1) [35].
The role of microbiota in mucosal homeostasis and immunological tolerance in healthy gut and activated inflammatory cascades in endocrine autoimmune disease. In germ-free animals, GALT structures are less developed and the microbiota has a major influence on the development of T lymphocyte subpopulations and in maintaining the numerical balance of Th-2/Th-1 lymphocyte populations in lymphoid organs. The healthy gut environment is characterized by high levels of antimicrobial peptides and metabolites (SCFAs), and the commensal-specific IgA is produced by plasma cells in the lamina propria, mediated by DCs in a T cell-independent mechanism. During homeostasis, gut microorganisms induce an immune tolerance phenotype in the host, whilst in inflammatory conditions, antigens from dysbiotic microorganisms activate Th1 and Th17 cells leading to decreased mucus layer, tissue injury, and microbial penetration and persistence in the intestinal tissues. This mucosal injury results in further uptake of microbial antigens that further perpetuate detrimental immune responses. Figure created with
Although the autoimmune conflict occurs most of the time without clinical manifestations, it can generate under certain conditions, such as AIDS, that are characterized by the appearance of tissue lesions or disruption of physiological processes. AIDS have a multifactorial etiology involving genetic, epigenetic, and environmental factors. It is estimated that 70% of AIDS are due to environmental factors [36]. Among the multiple cellular and molecular mechanisms, yet not well established, by which the state of immune self-tolerance is disturbed, we can mention—(i) the genetic predisposition that may explain the familial character of AIDS, which, in general, have a polygenic determinism. The risk of a certain autoimmune disease for monozygotic twins is about 12 to 60%, and for dizygotic twins is 5%. The most important are certain specific polymorphisms generated by the change of a nucleotide, that is, SNP (single nucleotide polymorphism) in MHC genes [9]. For example, over 90% of Caucasians with ankylosing spondylitis express an allele of the HLA-B27 family, differing from that of normal individuals by two amino acids located in the peptide binding groove [37]; (ii) release of sequestered antigens after trauma, surgery, infectious processes, etc., become accessible to lymphocytes, triggering the autoimmune conflict and tissue damage (e.g., basic myelin protein in the central nervous system becomes the antigenic target in multiple sclerosis; crystalline proteins induce autoimmune ophthalmopathy; sperm proteins, in cases of sperm stasis, induce the synthesis of immobilizing or binder autoantibodies of sperm, leading to autoimmune infertility) [38, 39]; (iii) modification of the chemical structure of autoantigens (so-called altered self-theory), which occurs under the influence of some physical factors (such as burns or radiation), biological (i.e., bacteria, viruses, fungi), or chemical (i.e., drugs, alcohol) factors, with the exposure of some new antigenic determinants [40]; (iv) infectious agents, which may have an important role in triggering AIDS by various mechanisms, such as the antigenic resemblance of non-self to self-molecules and their cross-reactivity (e.g., protein M from
AIDS resemble some general features—the pathological process has an individual intensity, dynamics, and evolution, may overlap with the same patient, and are rare in childhood, except for type 1 diabetes mellitus.
Regardless of the triggering mechanism, AIDS is characterized by the synthesis of autoantibodies (that are antibodies specific to self-tissue components) or by the generation of autoreactive T lymphocytes. Tissue injuries following the action of immune effectors occur in one of the above-mentioned scenarios—(i) autoantibodies recognize the tissue antigens and form immune complexes, the complement is activated, and the result is the cell lysis, or (ii) indirect action, in which case, the antigen-antibody—complement immune complexes are deposited in small vessels (arterioles, capillaries) from various organs and produces inflammatory reactions, with the consequence of tissue destruction; the AIDS that are mediated by various antibodies have a common feature, that is the target tissue is damaged by a chronic inflammatory reaction without a known infectious cause; and (iii) the lesions in the target tissue occur under the action of infiltrated Tc lymphocytes [43, 44].
Some AIDS are characterized by strictly localized pathological processes, that is, effectors (especially antibodies) have specific action against antigens specific to the target tissue (such is the case for autoantibodies specific only to B cells from Langerhans islands in type 1 diabetes mellitus, or autoantibodies specific to thyroid epithelial cell in Hashimoto’s thyroiditis) [45], sometimes the lesions are localized in a single organ, but autoantibodies do not have organ specificity (for instance, anti-mitochondrial antibodies in primary cirrhosis, or type IV anti-collagen autoantibodies in Goodpasture syndrome) [46, 47] while some AIDS are disseminated, characterized by the synthesis of autoantibodies to antigens with wide tissue distribution (e.g., antinuclear antibodies in systemic/disseminated lupus erythematosus) [48].
Often, in pathological cases, the body synthesizes auto-antibodies specific for components of the endocrine system, especially antibodies specific for a certain hormone receptor. The pathophysiological effects of these antibodies generated against hormone receptors are varied—they can stimulate the activity of the receptor, and the effect is to intensify the secretory activity of the gland (hormonal mimetic effect) or block the receptor, and the effect is to inhibit the secretory activity. Both antibodies can coexist in the same patient.
The role of the microbiota in autoimmune pathology has been highlighted by experimental data collected from germ-free mice. The intestinal microbiota maintains the balance of protective reactions to pathogens and tolerance to commensals aimed at maintaining intestinal homeostasis [49, 50]. Alterations produced in the balance of the microbiota (that is dysbiosis) activate the proinflammatory immune response and favor the progression of autoimmune disorders, such as multiple sclerosis, inflammatory bowel disease, T1DM, rheumatoid arthritis, and other pathologies of the digestive tract and ancillary glands, including malignancies. However, the intimate mechanism of microbiota involvement in this pathogenesis remains unknown [51, 52, 53].
AIDS are caused primarily by predisposing genetic factors but also by other endogenous or environmental triggers. There is a permanent interaction of the local immune system with bacterial antigens in humans, and therefore dysbiosis of the microbiome is associated with autoimmune disorders and metabolic syndromes. Dysbiosis means, in fact, the numerical alteration, diversity, and physiology of the intestinal microbiota (the transcriptome, proteome, and metabolome change) [54].
Experimental results in germ-free or induced dysbiotic animals support either the microbiota’s direct or indirect involvement in the pathogenesis of some AIDS. Hence, in patients with type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, or lupus, as in those suffering from inflammatory bowel disease (both Chron’s disease and ulcerative colitis), Sjögren’s syndrome, Behcet’s disease, autoimmune skin diseases (such as vitiligo, psoriasis, atopic dermatitis), the digestive microbiota is altered in terms of diversity and numerical representation of some species [9, 18, 35]. Kriegel et al. consider that dysbiosis is an essential trigger of autoimmunity both at the mucosal and systemic levels [9]. The spread of autoimmune response seems to be generated either by disseminating bacterial antigens but mostly by cross-immune reactivity under homeostasis conditions [55]. Such a mechanism is supported by a rheumatic fever induced by M and SLO antigens of
Type 1 diabetes mellitus (T1DM) has a well-defined autoimmune component, characterized by selective immune aggression against β-cells that secrete insulin [57]. The genetic predisposition for T1DM is unanimously accepted, but the interaction of genetic factors with environmental ones explains the sudden increase in incidence in Western countries [58]. More than 50% of monozygotic twins who have a sibling with T1DM remain healthy, showing that environmental factors (such as infectious agents, consumption of cow’s milk in early childhood, or ingestion of contaminated food) play a major role in triggering the disease. Hence, out of 50 individuals suffering from congenital rubella virus infection [59, 60], nine developed diabetes at an average age of 28 years. However, some infections (i.e.,
The pathological mechanisms leading to the autoimmune destruction of pancreatic beta-cells in T1DM are very complex and incompletely elucidated. The pancreatic beta-cells express MHC II and co-stimulatory molecules, suggesting their role as antigen-presenting cells to TCD4 cells. Auto-antigens that stimulate the specific immune reactivity against pancreatic beta-cell are represented by insulin, glutamic acid decarboxylase—isoform 2 of 65 kD from beta-cell cytoplasm, a Zn transporter protein (ZnT8) involved in active secretion of insulin from islet granules, insulinoma-associated antigen 2 (alpha and beta), and a membrane protein acting as tyrosine phosphatase. The presence of humoral autoimmunity defines the risk of T1DM; antibodies against insulin were identified in 40% of children with the overt disease [65].
In patients with T1DM, it has been shown by immunohistochemical staining that the islets are infiltrated with macrophages, dendritic cells, TCD4, TCD8, NK, and fewer B lymphocytes, which can act as antigen-presenting cells for TCD4 cells. The immune response against islet antigens is associated with an inflammatory one in which IL-1, TNFα, and IFNγ are released [66]. The immune and inflammatory process destroys the beta cells. When about 80% of the beta-cell mass has been destroyed, the disease overt. This silent period may last for several years, sometimes decades. Along with the progressive destruction of β cells, the humoral antibody response and decreased glucose tolerance are documented until the clinical onset of the disease. Immune effectors selectively lyse insular β cells, leaving the other cell types intact. After the onset of hyperglycemia, the degree of mononuclear infiltration decreases [67].
The inflammatory diseases of the pancreas (such as chronic pancreatitis, neoplasia) are characterized by mast cells infiltrates into the acinar parenchyma, which releases various proteases (chymase, tryptase), acting as direct destroyers on islet’s beta cells. The B4 type of leukotrienes, which derives from mast cells, exerts a chemoattractant effect on T lymphocytes [68].
Loss of pancreatic beta cells leads to insulin secretion deficiency, while the glucagon secretion becomes excessive and disrupts metabolism, resulting (in the absence of insulin) in diabetic ketoacidosis [69].
The experimental results argue for the interference of the microbiota and T1DM pathological mechanisms—the incidence of diabetes is higher in mice raised in aseptic conditions, and the antibiotics administered to conventional animals accelerate the evolution of diabetic pathology. The NOD (non-obese diabetes) mice have a distinct microbiota from other resistant lines, and the incidence of type 1 diabetes mellitus is higher in specific pathogen-free animals [70].
Dysbiosis is shaped by host-related individual factors and early-life exposure to certain microorganisms, and its alterations undergo extensive changes with the change in diet. The permeability of the intestinal barrier plays an important role in the initiation and evolution of autoimmune conflict, aside from the background of genetic predisposition. The intercellular tight junctions control the permeability of the epithelium, allowing the absorption of nutrients, but preventing the passage of various environmental antigens (i.e., food, bacterial, viral, and fungal). Dysbiosis decreases intestinal permeability and facilitates the translocation of bacterial antigens [52].
Microbiota derangements have been implicated in the evolution of both T1DM and T2DM [71]. Dysbiosis occurs very early in subjects with a genetic predisposition for T1DM, probably since the neonatal period [51]. It is unknown whether the genetic predisposition to T1DM shapes the microbiota of high-risk individuals or whether the microbiota is the cause or effect of the disease [71].
As stated above, the human microbiota stabilizes during the first 3 years of life, while three parallel phenomena occur—(i) development of the immune system, (ii) maturation of the microbiota, and (iii) seroconversion to T1DM-associated autoantibodies. The possible conditioning of the two (i.e., seroconversion and T1DM occurrence) events is unknown. In a longitudinal study, Kostic et al. showed a decrease in the bacterial diversity of the microbiota that occurs before the development of the clinical disease in children positive for anti-insulin antibodies [70]. The
Furthermore, the microbiota changes evolve with disease progression [65].
The fungal microbiome of the human population is evaluated in 267 species, with the most commonly represented by g.
Despite the abundance of experimental and clinical results suggesting a bidirectional relationship between dysbiosis and T1DM onset and progress, there are questions that still need an answer—(i) is their relationship causal or simultaneous? and (ii) the condition of causality is that the change of one variable leads to the change of another repeatedly and generally? [65].
Thyroid AIDS are conditioned as other auto-immunities by a genetic predisposition, but other factors play an important role in triggering and evolving the autoimmune pathological process [72]. They occur with a frequency of about 4% in the human population and express by either hyper- or hypothyroidism. In both cases, the thyroid may increase in volume (goiter), while ophthalmopathy may develop in hyperthyroidism only [73]. Autoimmune thyroid disease affects especially women and from an immunological point of view, it is characterized by the presence of circulating autoantibodies, activated T cells against thyroid antigens, and by lymphocytic infiltration of the organ. Three specificities of anti-thyroid autoantibodies have been described—anti-thyroid peroxidase (microsomal antigen); anti-thyroglobulin; anti-TSH receptor of thyroid acinar cells [74, 75].
AIDS that cause thyroid failure, generically called thyroiditis, are characterized by lymphocytic infiltration. Depending on the clinical aspects there are two pathological conditions—Hashimoto’s thyroiditis and atrophic thyroiditis (primary myxedema). In both cases, the thyroid tissue is lysed. Autoimmune thyroid disease is influenced by various factors, such as age, sex, race, and hormonal status [76, 77].
Autoimmune thyroid diseases (Graves and Hashimoto’s thyroiditis) often coexist with intestinal diseases, especially celiac disease. The composition of the microbiota population is influenced by diet, affects the thyroid function, mostly by providing the micronutrients essential for the synthesis of thyroid hormones—iodine, iron, and copper. Selenium and zinc are essential for the conversion of T4 to T3, and vitamin D has an immune regulatory effect. Probiotic supplementation favorably influences the secretion of thyroid hormones [26].
Autoimmune thyroiditis is the most common thyroid disorder, with a prevalence of 10–12%. It is triggered by genetic and environmental factors (viral infections) and has an increased prevalence in patients with celiac disease. The commensal microbiota activates the proinflammatory response through innate immunity receptors from the toll-like receptor family and disrupts the intestinal permeability, which may be a triggering factor for Hashimoto’s thyroiditis [78].
Hashimoto’s thyroiditis is the most common endocrine AIDS (i.e., 10–12% of total autoimmune endocrinopathies), which is characterized by autoimmune destruction of thyroid follicles. The incidence increases with age and is 10 times higher in women. In the serum of patients with Hashimoto’s thyroiditis are detected various specific autoantibodies, such as anti-thyroglobulin and/or anti-TPO (thyroid-peroxidase), anti-TSH receptor. Definitive for Hashimoto’s disease is the replacement of thyroid tissue with lymphoid tissue. An impressive increase in thyroid volume may be observed, but no hormones are synthesized instead (dry goiter). The symptoms of Hashimoto’s thyroiditis and celiac disease often overlap and share epidemiological, clinical, serological, pathological, hormonal, genetic, and immune similarities. Microbiome analysis performed on patients with this ailment revealed that abundance levels of
Celiac disease (CD) is an autoimmune condition characterized by a specific serological and histological profile triggered by gluten ingestion in genetically predisposed individuals [83]. CD is the only AID known to be triggered by an exogenous antigen, that is, wheat gluten. Gluten is a mixture of proteins grouped in the fraction of gliadin and glutenin, which is the source of carbon and nitrogen for germinating seedlings. Gliadin triggers specific auto-antibody synthesis, the clinical feature being strictly dependent on dietary exposure to gluten and homologous proteins from other cereals. CD is one of the most common autoimmune disorders, with a reported prevalence of 0.5–1% of the general population, except in areas showing a low frequency of CD-predisposing genes and low gluten consumption [84]. Studies have shown that most CD cases remain undetected in the absence of serological screening due to heterogeneous symptoms and/or poor disease awareness. CD has a strong hereditary component confirmed by its high familial recurrence (~10–15%) and the high concordance of the disease among monozygotic twins (75–80%) [85]. Also common to other AIDS, the HLA class II heterodimers, specifically DQ2 and DQ8, have a relevant role, in the heritability of CD. HLA-DQ2 homozygosis confers a much higher risk (25–30%) of developing early-onset CD in infants with a first-degree family member affected by the disease [86].
Dysbiosis is considered an important factor in the interaction of intestinal and thyroid AIDS. The mechanisms that mediate the interaction of microbiota imbalance and thyroid auto-immunities include: (i) intestinal dysbiosis, which interrupts self-tolerance and tolerance to non-pathogenic bacteria, by post-translational modification of proteins. The bacterial enzymatic apparatus can transform the self or nonself peptide into initiators of the autoimmune reaction, (ii) lipopolysaccharides-induced TLR activation, which is associated with thyroiditis and synthesis of anti-thyroglobulin antibodies, (iii) induction of Th-2 lymphocyte differentiation, inhibition of Th-17 lymphocyte differentiation and induction of oral acid tolerance to retinoic acid, which can activate an immune response of tolerance at intestinal level, (iv) permeabilization of the intestinal barrier through injuries of the integrity of tight junctions, deficiency of butyric acid produced by the fermented components in the microbiota or excess of ingested proteins that are metabolized by the microbiota with an increase of putrefaction components; all these factors increase the permeability of the intestinal barrier, facilitating the passage of gliadin and activation of the immune response [26]; (v) changes in the transcriptome, proteome and metabolome of the microbiota [34].
Hashimoto’s thyroiditis and CD share common antibodies, that is anti-tissular transglutaminase (anti-tTg). In patients with CD, tTg binds to the thyroid follicles and the extracellular matrix of the follicles, therefore amplifying the interactions of the microbiota with the thyroid tissue. There is a direct correlation between serum titers of anti-tTg anti-TPO antibodies. DR3-DQ2 and DR4-DQ8 alleles, involved in CD, are reported as common genes that predispose to endocrine AIDS [80].
Rheumatoid arthritis is characterized by a severe and chronic inflammatory condition of the joints. The clinical course of the disease underlines the potential role of dysbiosis in triggering an inflammatory process that involves autoimmune components [87]. Germ-free animals are protected from rheumatoid arthritis in experimental settings. However, the disease is induced in mice exposed to
Periodontitis that is caused by oral microbiota bacteria progresses similarly to rheumatoid arthritis—leukocyte infiltration and the progressive destruction of alveolar bone. Leukocytes release the set of proinflammatory interleukins (such as TNF, Il-1, IL-6, IL-12, IL-17, IL-18, and IL-33), growth factors (such as colony-stimulating factors—i.e., GM-CSF, monocyte-CSF), activator receptor of nuclear factor kappa-β ligand (RANKL), metalloproteases, nitric oxide, and PG E2 [89].
In 2013, Rinaldi identified auto-antibodies against the cellular wall of
Behcet’s disease is a chronic, multisystemic inflammation that is characterized by uveitis, which is a major cause of blindness, and recurrent ulcerative lesions involving the mouth and genital mucosa. There have been reported changes in Th-1, Th-17, and T-reg lymphocytes, whose activity is regulated by the microbiome [91], as well as the diversification of potentially pathogenic bacteria and the decrease of those that produce butyrate (
The pathological change in ulcerative colitis consists of diffuse inflammation, with limited ulcers in the chorion of the colonic mucosa. The pathological process is extended over the entire mucosa of the intestinal epithelium [92].
In Crohn’s disease, the inflammatory infiltrates often generate extensive granulomas in the submucosa and even in the muscular layer of the colon and small intestine. The pathological process of Crohn’s disease is localized, with the damaged areas of the intestine alternating with the healthy ones [93].
Crohn’s disease and ulcerative colitis are not AIDS in the strict sense, because triggering antigens appear to be components of the intestinal microbiota translocated into the chorion, but are the consequence of a large immune response in non-pathogenic antigens, which occurs in people with a genetic predisposition. The inflammatory condition increases the permeability of the colonic epithelium, and the microbiome is modified—the method of 16S rDNA sequencing has shown a decrease in bacterial diversity, especially of the non-pathogenic population, in favor of potentially pathogenic ones [94].
Lupus erythematosus is the prototype of systemic autoimmune disease—an autoimmune response characterized by hyper-reactivity of B lymphocytes and the presence of a large spectrum of serum antibodies [95]. As its name, the disease involves many organs and systems and has various clinical manifestations. Lupus erythematosus affects especially women (female/male ratio = 9/1), with the highest risk during pregnancy [96]. The intestinal microbiota is altered—depletion of lactobacilli, increased
Multiple sclerosis is a chronic demyelinating inflammatory disease of the central nervous system, characterized by destruction of the integrity of the haemato-encephalic barrier, T lymphocyte infiltrates, and autoimmune reaction against myelin proteins [99]. The immune response in experimental autoimmune encephalitis is mediated by Th-1 and Th-17 cells. The causative agent is not known, but the modification of the microbiota may be important in the onset and/or progression of autoimmune disease. The autoimmune encephalitis diminishes to extinction in
The liver autoimmune disease appears to have a direct connection to the microbial load (cells, lipopolysaccharides, peptidoglycans, flagellin, DNA, RNA, toxins, and metabolites) that reaches the Kupffer cells and sinusoidal capillaries by passaging the portal vein. The immune response to these antigens can initiate liver damage and fibrosis [55, 101].
Vitiligo is a systemic autoimmune disease, which is characterized by areas of skin depigmentation, as a result of melanocyte lysis under the action of TCD8 lymphocytes. Melanocytes are located at the border between the epidermis and the dermis, but the disease is systemic because melanocytes are also found in other tissues. The number of melanocytes is the same in different individuals, but differences in pigmentation result from the number, distribution, and size of melanosomes in keratinocytes. The intestinal microbiota in patients with vitiligo is altered and is characterized by decreased taxonomic diversity [18, 102].
Atopic dermatitis is an inflammatory skin disease, clinically characterized by pruritus and xerosis (dry skin). The underlying cause is delayed hypersensitivity mediated by T lymphocytes. The local trigger is the colonization of the skin with
Intestinal dysbiosis alters the permeability of the intestinal barrier. The passage of the microbiota antigens into the internal environment may induce the loss of self-tolerance with the generation of autoantibodies and/or autoreactive T cells, leading to the occurrence of cross-reactions. The microbiota alterations lead to an increase in enteric barrier permeability and the occurrence of lymphocyte infiltrates into the epithelial layer, augmenting the risk of cell-mediated auto-immune response. Many questions still need an answer about the role of the microbiota in triggering AIDS, such as—what are the roles of sex hormones and the role of X-linked genes expression in correlation with the microbiome in the polarization of gender-dependent AIDS. Do the changes in the microbiota, which are reported by many authors, contribute to the onset of AIDS by breaking the peripheric tolerance or they are the consequence of AIDS?
This research was funded by projects PD224/2021 (PD-2019-0499) and PFE-CDI.2021-587.
The authors declare no conflict of interest.
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...)
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\\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
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Bücking"},{id:"145611",title:"MSc.",name:"Prashant",middleName:null,surname:"Ambilwade",slug:"prashant-ambilwade",fullName:"Prashant Ambilwade"},{id:"145612",title:"MSc.",name:"Elliot",middleName:null,surname:"Liepold",slug:"elliot-liepold",fullName:"Elliot Liepold"}]},{id:"61312",doi:"10.5772/intechopen.74425",title:"Nanotechnology in Agriculture: New Opportunities and Perspectives",slug:"nanotechnology-in-agriculture-new-opportunities-and-perspectives",totalDownloads:3184,totalCrossrefCites:17,totalDimensionsCites:45,abstract:"The prediction that in 2050 our planet will be populated by over 9 billion people is quite reliable. This will pose serious problems with food, water and energy supply, particularly in less-developed countries. Considering that the human pressure over natural resources has already reached critical levels, international agencies such as the World Bank and UN Food and Agriculture Organization (FAO) are soliciting scientific research in order to identify innovative solutions to support the primary sector. Nanotechnology is a rapidly evolving field with the potential to take forward the agriculture and food industry with new tools which promise to increase food production in a sustainable manner and to protect crops from pests. Such expectations are coupled with some uncertainties about the fate of nanomaterials in the agro-environment. However, the field application of engineered nanomaterials (ENMs) has not been properly investigated yet, and many aspects have only been considered theoretically or with models, which make it difficult to properly assess the usefulness of ENMs for plant fertilization and protection.",book:{id:"6763",slug:"new-visions-in-plant-science",title:"New Visions in Plant Science",fullTitle:"New Visions in Plant Science"},signatures:"Luca Marchiol",authors:[{id:"163884",title:"Prof.",name:"Luca",middleName:null,surname:"Marchiol",slug:"luca-marchiol",fullName:"Luca Marchiol"}]},{id:"67311",doi:"10.5772/intechopen.86341",title:"Wheat Production in India: Trends and Prospects",slug:"wheat-production-in-india-trends-and-prospects",totalDownloads:2333,totalCrossrefCites:26,totalDimensionsCites:37,abstract:"Trends in Indian wheat production before and after the inception of the All India Coordinated Research Project (AICRP) on wheat have been analyzed to show its significant progress over the years. A brief intercountry comparison of productivity, production and area coupled with regional comparison within India has been attempted to give an idea about the contribution of country and regions, respectively, for global and national food security. The milestones in Indian wheat programme and research outcomes were highlighted post-AICRP along with the vision and strategies set for 2050 against diverse production challenges. Regional disparities, zone-wise production constraints and research programmes for achieving the set production target were briefed. The chapter concludes with possible interventions in strengthening the complete wheat value chain for ensuring food security for the future generation.",book:{id:"8168",slug:"recent-advances-in-grain-crops-research",title:"Recent Advances in Grain Crops Research",fullTitle:"Recent Advances in Grain Crops Research"},signatures:"Sendhil Ramadas, T.M. 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Mostafa",authors:[{id:"68104",title:"Prof.",name:"Soha",middleName:"Sayed Mohammad",surname:"Mostafa",slug:"soha-mostafa",fullName:"Soha Mostafa"}]},{id:"68218",doi:"10.5772/intechopen.87069",title:"Neglected and Underutilized Legume Crops: Improvement and Future Prospects",slug:"neglected-and-underutilized-legume-crops-improvement-and-future-prospects",totalDownloads:1803,totalCrossrefCites:10,totalDimensionsCites:21,abstract:"Sustainable agricultural productivity is hampered by over-dependency on major staple crops, neglect and underutilization of others, climate change, as well as land deterioration. Challenges posed by these limiting factors are undoubtedly contributing to global food insecurity, increased rural poverty, and malnutrition in the less developed countries. Miscellaneous neglected and underutilized grain legumes (MNUGLs) are crops primarily characterized by inherent features and capabilities to withstand the effects of abiotic stress and climate change, significantly replenish the soil, as well as boost food and protein security. This chapter provides insight into the benefits of MNUGLs as food and nutritional security climate smart crops, capable of growing on marginal lands. Exploring and improving MNUGLs depend on a number of factors among which are concerted research efforts, cultivation and production, as well as utilization awareness across global populace geared toward reawakening the interest on the abandoned legumes. The emergence of the clustered regularly interspaced short palindromic repeat (CRISPR/cas9) technology combined with marker-assisted selection (MAS) offers great opportunities to improve MNUGLs for sustainable utilization. Advances in improvement of MNUGLs using omic technologies and the prospects for their genetic modification were highlighted and discussed.",book:{id:"8168",slug:"recent-advances-in-grain-crops-research",title:"Recent Advances in Grain Crops Research",fullTitle:"Recent Advances in Grain Crops Research"},signatures:"Jacob Popoola, Omena Ojuederie, Conrad Omonhinmin and Adegoke Adegbite",authors:[{id:"246358",title:"Prof.",name:"Conrad",middleName:null,surname:"Omonhinmin",slug:"conrad-omonhinmin",fullName:"Conrad Omonhinmin"},{id:"294662",title:"Dr.",name:"Omena",middleName:null,surname:"Ojuederie",slug:"omena-ojuederie",fullName:"Omena Ojuederie"},{id:"294740",title:"Dr.",name:"Jacob",middleName:null,surname:"Popoola",slug:"jacob-popoola",fullName:"Jacob Popoola"},{id:"294766",title:"Prof.",name:"Adegoke",middleName:null,surname:"Adegbite",slug:"adegoke-adegbite",fullName:"Adegoke Adegbite"}]}],mostDownloadedChaptersLast30Days:[{id:"63134",title:"Transgenic Plants: Gene Constructs, Vector and Transformation Method",slug:"transgenic-plants-gene-constructs-vector-and-transformation-method",totalDownloads:5501,totalCrossrefCites:9,totalDimensionsCites:19,abstract:"The human population has reached 7 billion by 2015 and is estimated to exceed 10 billion by the end of 2050. As such, crops which are the main food source must be produced at a higher pace in order to cater in tandem with the food demand. In the past, traditional plant breeders practice classical breeding techniques to propagate plants with desirable traits. However, traditional breeding technique lies in that only individuals of the same or closely related species can be crossbred. Moreover, traditional breeders will not be able to obtain traits which are not inherent within the gene pool of their target plants through classical breeding. With recent advancements in the field of genetic engineering, it is now possible to insert beneficial genes from a completely different species or even kingdom into a target plant, yielding transgenic plants with multiple ideal traits. To develop a transgenic plant, parameters such as vector constructions, transformation methods, transgene integration, and inheritance of transgene need to be carefully considered to ensure the success of the transformation event. Hence, this chapter aimed to provide an overview of transgenic plants’ development, its advantages and disadvantages, as well as its application for the betterment of mankind.",book:{id:"6763",slug:"new-visions-in-plant-science",title:"New Visions in Plant Science",fullTitle:"New Visions in Plant Science"},signatures:"Lee-Yoon Low, Shun-Kai Yang, De-Xian Andrew Kok, Janna Ong-\nAbdullah, Ngai-Paing Tan and Kok-Song Lai",authors:[{id:"195386",title:"BSc.",name:"Shun Kai",middleName:null,surname:"Yang",slug:"shun-kai-yang",fullName:"Shun Kai Yang"},{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai"},{id:"240035",title:"Ms.",name:"Lee Yoon",middleName:null,surname:"Low",slug:"lee-yoon-low",fullName:"Lee Yoon Low"},{id:"240036",title:"Mr.",name:"Kok",middleName:null,surname:"Andrew-De-Xian",slug:"kok-andrew-de-xian",fullName:"Kok Andrew-De-Xian"},{id:"257891",title:"Dr.",name:"Janna Ong",middleName:null,surname:"Abdullah",slug:"janna-ong-abdullah",fullName:"Janna Ong Abdullah"},{id:"257892",title:"Dr.",name:"Ngai Paing",middleName:null,surname:"Tan",slug:"ngai-paing-tan",fullName:"Ngai Paing Tan"}]},{id:"67311",title:"Wheat Production in India: Trends and Prospects",slug:"wheat-production-in-india-trends-and-prospects",totalDownloads:2335,totalCrossrefCites:26,totalDimensionsCites:37,abstract:"Trends in Indian wheat production before and after the inception of the All India Coordinated Research Project (AICRP) on wheat have been analyzed to show its significant progress over the years. A brief intercountry comparison of productivity, production and area coupled with regional comparison within India has been attempted to give an idea about the contribution of country and regions, respectively, for global and national food security. The milestones in Indian wheat programme and research outcomes were highlighted post-AICRP along with the vision and strategies set for 2050 against diverse production challenges. Regional disparities, zone-wise production constraints and research programmes for achieving the set production target were briefed. The chapter concludes with possible interventions in strengthening the complete wheat value chain for ensuring food security for the future generation.",book:{id:"8168",slug:"recent-advances-in-grain-crops-research",title:"Recent Advances in Grain Crops Research",fullTitle:"Recent Advances in Grain Crops Research"},signatures:"Sendhil Ramadas, T.M. 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Therefore, a full understanding of plant-NP interaction and phytotoxicological mechanism is required for accurate risk assessment to ensure the safe use of nanoparticle. A range of analytical techniques have been developed to detect and characterize the uptake, translocation, cellular internalization and intracellular biotransformation of nanoparticles in plants. Imaging methodologies, including various electron microscopy, spectrometry-based techniques, together with ICP-based techniques such as ICP-OES, ICP-MS and SP-ICP-MS, have been widely used to obtain information about NPs size, morphology, size distribution, cellular localization, elemental speciation, mass concentration and so on. Due to the complexity of biological samples to be analyzed, these techniques are often combined accordingly to provide complementary information regarding plant-NP interaction. This review provides an introduction to the most widely used techniques in the study of interactions between plants and nanoparticles. In addition, applications of these techniques in the study of plant-NP interaction from recent works are exemplified to illustrate how the understanding of plant-NP interaction is achieved through these techniques.",book:{id:"6763",slug:"new-visions-in-plant-science",title:"New Visions in Plant Science",fullTitle:"New Visions in Plant Science"},signatures:"An Yan and Zhong Chen",authors:[{id:"230515",title:"Assistant Prof.",name:"Zhong",middleName:null,surname:"Chen",slug:"zhong-chen",fullName:"Zhong Chen"},{id:"239423",title:"Dr.",name:"An",middleName:null,surname:"Yan",slug:"an-yan",fullName:"An Yan"}]},{id:"41640",title:"The Role of the Mycorrhizal Symbiosis in Nutrient Uptake of Plants and the Regulatory Mechanisms Underlying These Transport Processes",slug:"the-role-of-the-mycorrhizal-symbiosis-in-nutrient-uptake-of-plants-and-the-regulatory-mechanisms-und",totalDownloads:9065,totalCrossrefCites:31,totalDimensionsCites:67,abstract:null,book:{id:"2635",slug:"plant-science",title:"Plant Science",fullTitle:"Plant Science"},signatures:"Heike Bücking, Elliot Liepold and Prashant Ambilwade",authors:[{id:"145162",title:"Prof.",name:"Heike",middleName:null,surname:"Bücking",slug:"heike-bucking",fullName:"Heike Bücking"},{id:"145611",title:"MSc.",name:"Prashant",middleName:null,surname:"Ambilwade",slug:"prashant-ambilwade",fullName:"Prashant Ambilwade"},{id:"145612",title:"MSc.",name:"Elliot",middleName:null,surname:"Liepold",slug:"elliot-liepold",fullName:"Elliot Liepold"}]},{id:"41644",title:"Effects of White Root Rot Disease on Hevea brasiliensis (Muell. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. 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Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. 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Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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