\r\n\tEqually important are the consequences deriving from the extraordinary nature of the present times. The COVID-19 pandemic and the restrictive measures to contain the infection (lockdown and "physical distancing" in primis) have revolutionized the lives, and a distortion/modification of habits, rhythms, arrangements will continue to be necessary.
\r\n\tGovernments have implemented a series of actions to mitigate the spread of infections and alleviate the consequent pressure on the hospital system. On the other hand, the Covid-19 pandemic has caused a series of other cascading effects that will probably be much more difficult to mitigate and which expose to complex consequences. The past two years have brought many challenges, particularly for healthcare professionals, students, family members of COVID-19 patients, people with mental disorders, the frail, the elderly, and more generally those in disadvantaged socio-economic conditions, and workers whose livelihoods have been threatened. Indeed, the substantial economic impact of the pandemic may hinder progress towards economic growth as well as progress towards social inclusion and mental well-being.
\r\n\t
\r\n\tAlthough in all countries the knowledge on the impact of the pandemic on mental health is still limited and mostly derived from experiences only partially comparable to the current epidemic, such as those referring to the SARS or Ebola epidemics, it is likely that the demand for intervention it will increase significantly in the coming months and years. The extraordinary growth of scientific research in the field of neuroscience now offers the possibility of a new perspective on the relationship between mind and brain and generates new scenarios in understanding the long wave of the pandemic and in the prospects for treatment. Moreover, the pandemic also has led to opportunities to implement remote monitoring and management interventions.
\r\n\t
\r\n\tOverall this volume will address the complex relationship existing between COVID-19, mental health, acquired knowledge, and possible interventions taking a highly multidisciplinary approach; from physiological and psychobiological mechanisms, and neuromodulation through medical treatment, psychosocial interventions, and self-management.
Immune tolerance is a physiological condition, characterized by the absence of an immune response to a specific antigen and the retention of the ability to develop an immune response to other different antigens. 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.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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One of the most suitable examples of nanoparticles used for this purpose are quantum dots, a type of colloidal fluorescent semiconducting nanocrystalline material that has the possibility, due to its unique optical and electronic properties, to be used in numerous technological applications such as biosensing, in vivo imaging techniques, photovoltaics, nanomedicine, molecular pathology, and drug delivery. Thus, there are almost endless possibilities for quantum dots materials. In spite of the fast advance in the search of quantum dots with better nanomaterial performance, environmentally benign and sustainable production is still lacking. Although the use of these materials is developing promptly, there is increasing concern that these materials might pose potential risks to human health. Herein, we discuss principal properties of quantum dots, including their functional architecture and toxicity, and review the main studies about “green” quantum dots synthesis to be aligned with green nanotechnology approach for nontoxic, cleaner, safer, and more responsible processes. The organometallic colloidal synthesis and the aqueous colloidal synthesis, as well as their drawbacks and benefits, are conferred. Recent advances in technological and biological quantum dots–based applications are also discussed in this chapter.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Carlos A. Martínez Bonilla and Vladimir V. Kouznetsov",authors:[{id:"105180",title:"Prof.",name:"Vladimir V.",middleName:"V.",surname:"Kouznetsov",slug:"vladimir-v.-kouznetsov",fullName:"Vladimir V. 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In this sense, new materials such as nanocomposites may overcome these issues taking advantage of the peculiar properties of materials at nanoscale. Research on novel nanotechnologies must bring advances in order to contrast and prevent water scarcity and pollution. 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It is linked with the implementation of products of nanotechnology and its process of manufacturing. Green nanotechnology synthesizes new nanoproducts with improved properties in such a way that they can substitute some of the existing low‐quality products. The main motive of developing new nanoproducts is to enhance sustainability and also to make them more environment friendly. In particular, nanoscale materials (e.g., nanoparticles) can be defined as those having characteristic length scale lying within the nanometric range, that is, in the range between one and several hundreds of nanometers. Within this length scale, the properties of matter are sufficiently different from individual atoms/molecules or from bulk materials. The primary objective of this chapter is to provide comprehensive overview about metal nanoparticles (MNPs) and its application as emerging green catalysts. This chapter contains six sections in total. Section 1 starts with a general introduction, recent progress, and brief summary of the application of MNPs as green catalyst. Section 2 reviews the preparation and characterization of supported metal nanoparticles for a wide range of catalytic applications. Section 3 presents the catalytic properties of supported metal nanoparticles. Section 4 describes briefly some of the most commonly reported supported MNPs in different green catalytic applications. Section 5 concentrates on our own results that related to the application of supported MNPs in catalysis. In this section, the oxidation of benzyl alcohol to benzaldehyde, the production of adipic acid from cyclohexane, the photodegradation of dyes using green route will be discussed. 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The SAR (structure-activity relationship) and STAR (structure-thermodynamics activity relationship) have been the most intimate theories in understanding and finding unique applications of the new molecules. Initially, simple molecules are the focus; however, proteins, hemoglobin, starch, and certain metallic complexes are also in the focus but as natural chemicals; but for past few decades, a lot of focus has been on synthesizing new complex molecules to make them suitable for varieties of applications such as solar, catalysts, biosensors, and others. Hence, it has been essential for focusing on structural sciences of the chemical substances. Dendrimers have been the invention of 1990s in the areas of biocomplexes, biomaterials which are hot thrust areas in molecular interaction engineering to focus on intramolecular potential for industrial applications. Thus, the molecule’s internal structure signifies the various scientific components for playing or making their best use in materials sciences, semiconductor, spintronics, photonics, electronics, etc. Therefore, the molecule’s interacting response with other molecules becomes cohesive or kinetic in nature or whether it induces structuredness or weakens the binding forces and allows more and more kinetic movement or the motion is noted or defined by friccohesity as it is expressed as frictional and cohesive forces. Thus, the friccohesity is a dual forces theory which deals with frictional and cohesive forces together and determined with Survismeter using Mansingh equation molecules [1–3].",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Man Singh",authors:[{id:"24553",title:"Prof.",name:"Man",middleName:null,surname:"Singh",slug:"man-singh",fullName:"Man Singh"}]}],mostDownloadedChaptersLast30Days:[{id:"50106",title:"“Green” Quantum Dots: Basics, Green Synthesis, and Nanotechnological Applications",slug:"-green-quantum-dots-basics-green-synthesis-and-nanotechnological-applications",totalDownloads:3775,totalCrossrefCites:9,totalDimensionsCites:19,abstract:"Nanotechnological development of new materials involves the discovery or design of materials at small length scales with controlled physical and chemical properties than can be tuned or modified in function of their applications. 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Herein, we discuss principal properties of quantum dots, including their functional architecture and toxicity, and review the main studies about “green” quantum dots synthesis to be aligned with green nanotechnology approach for nontoxic, cleaner, safer, and more responsible processes. The organometallic colloidal synthesis and the aqueous colloidal synthesis, as well as their drawbacks and benefits, are conferred. Recent advances in technological and biological quantum dots–based applications are also discussed in this chapter.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Carlos A. Martínez Bonilla and Vladimir V. Kouznetsov",authors:[{id:"105180",title:"Prof.",name:"Vladimir V.",middleName:"V.",surname:"Kouznetsov",slug:"vladimir-v.-kouznetsov",fullName:"Vladimir V. Kouznetsov"},{id:"179817",title:"M.Sc.",name:"Carlos A.",middleName:"Andrés",surname:"Martínez Bonilla",slug:"carlos-a.-martinez-bonilla",fullName:"Carlos A. Martínez Bonilla"}]},{id:"50705",title:"Metal Nanoparticles as Emerging Green Catalysts",slug:"metal-nanoparticles-as-emerging-green-catalysts",totalDownloads:3247,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Green nanotechnology is defined as the technology applied for building clean technology by which one can reduce the potential risks of environment and also improve human health conditions. It is linked with the implementation of products of nanotechnology and its process of manufacturing. Green nanotechnology synthesizes new nanoproducts with improved properties in such a way that they can substitute some of the existing low‐quality products. The main motive of developing new nanoproducts is to enhance sustainability and also to make them more environment friendly. In particular, nanoscale materials (e.g., nanoparticles) can be defined as those having characteristic length scale lying within the nanometric range, that is, in the range between one and several hundreds of nanometers. Within this length scale, the properties of matter are sufficiently different from individual atoms/molecules or from bulk materials. The primary objective of this chapter is to provide comprehensive overview about metal nanoparticles (MNPs) and its application as emerging green catalysts. This chapter contains six sections in total. Section 1 starts with a general introduction, recent progress, and brief summary of the application of MNPs as green catalyst. Section 2 reviews the preparation and characterization of supported metal nanoparticles for a wide range of catalytic applications. Section 3 presents the catalytic properties of supported metal nanoparticles. Section 4 describes briefly some of the most commonly reported supported MNPs in different green catalytic applications. Section 5 concentrates on our own results that related to the application of supported MNPs in catalysis. In this section, the oxidation of benzyl alcohol to benzaldehyde, the production of adipic acid from cyclohexane, the photodegradation of dyes using green route will be discussed. Finally, Section 6 describes the summary of main points and also presents an outlook of the application of MNPs in green chemistry.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Ahmad Alshammari, V. Narayana Kalevaru and Andreas Martin",authors:[{id:"178547",title:"Dr.",name:"Ahmad",middleName:null,surname:"Alshammari",slug:"ahmad-alshammari",fullName:"Ahmad Alshammari"},{id:"180753",title:"Dr.",name:"V. Narayana",middleName:null,surname:"Kalevaru",slug:"v.-narayana-kalevaru",fullName:"V. Narayana Kalevaru"},{id:"180804",title:"Dr.",name:"Andreas",middleName:null,surname:"Martin",slug:"andreas-martin",fullName:"Andreas Martin"}]},{id:"49331",title:"Metal Complexes Immobilized on Magnetic Nanoparticles",slug:"metal-complexes-immobilized-on-magnetic-nanoparticles",totalDownloads:2096,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The reusability of valuable catalysts in organic reaction without change in properties is known as an important feature in the evolution of green processes. The imobilization of metal catalysts on magnetic nanoparticles makes them recoverable and can be used as building blocks for the fabrication of various functional systems, which are applied in several fields such as catalysis, environmental remediation magnetic resonance imaging, data storage, and biotechnology. Applying magnetic nanoparticles in organic reaction as a scaffold for the immobilization of metal complexes is reviewed as well as the improvement of the methods of production and applying catalysts with magnetic properties in organic reaction.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Seyed Mohsen Sadeghzadeh and Mehdi Mogharabi",authors:[{id:"175879",title:"Dr.",name:"Seyed Mohsen",middleName:null,surname:"Sadeghzadeh",slug:"seyed-mohsen-sadeghzadeh",fullName:"Seyed Mohsen Sadeghzadeh"},{id:"191799",title:"Dr.",name:"Mehdi",middleName:null,surname:"Mogharabi",slug:"mehdi-mogharabi",fullName:"Mehdi Mogharabi"}]},{id:"50132",title:"Recent Highlights in Green Oxidative Chemical Processes Applied to Steroid Chemistry",slug:"recent-highlights-in-green-oxidative-chemical-processes-applied-to-steroid-chemistry",totalDownloads:2379,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Steroids and their oxidation products are widely distributed in living organisms and are important intermediates for the synthesis of many biologically active molecules. Due to their pharmacological and synthetic relevance, several oxidative chemical processes for the functionalization of the steroid nucleus have been developed. Green chemistry principles have been incorporated in some oxidative transformations of steroids, allowing significant advances in synthetic chemistry applied to these compounds. This chapter presents a selection of relevant applications of pharmaceutical green chemistry to steroid’s oxidative processes. Special emphasis is given to catalytic processes encompassing heterogeneous nanocatalysts, whose application in this context is increasing over the past years. This chapter is organized according to the reaction type that includes alcohol oxidation, epoxidation of alkenes, and allylic oxidation of alkenes to enones, among other relevant oxidative transformations. Biocatalytic oxidative methods applied to steroid synthesis are not included in this review.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Samuel M. Silvestre, M. Manuel C. Silva and Jorge A. R. Salvador",authors:[{id:"69976",title:"Prof.",name:"Jorge António Ribeiro",middleName:null,surname:"Salvador",slug:"jorge-antonio-ribeiro-salvador",fullName:"Jorge António Ribeiro Salvador"},{id:"157541",title:"Prof.",name:"Samuel",middleName:null,surname:"Silvestre",slug:"samuel-silvestre",fullName:"Samuel Silvestre"},{id:"185027",title:"Prof.",name:"Maria Manuel Cruz",middleName:null,surname:"Silva",slug:"maria-manuel-cruz-silva",fullName:"Maria Manuel Cruz Silva"}]},{id:"50074",title:"Nanostructured TiO2 Layers for Photovoltaic and Gas Sensing Applications",slug:"nanostructured-tio2-layers-for-photovoltaic-and-gas-sensing-applications",totalDownloads:2105,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Titanium dioxide (TiO2) has been an important material for decades, combining numerous attractive properties in terms of economy (low price, large availability) or ecology (non-toxic), as well as broad physical and chemical possibilities. In the last few years, the development of nanotechnologies offered new opportunities, not only in an academic perspective but also with a view to many applications with particular reference to the environment. This chapter focuses on the many ways that allow to tailor and organize TiO2 crystallites at the nanometre scale to make the most of this amazing material in the field of photovoltaics and gas sensing.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"André Decroly, Arnaud Krumpmann, Marc Debliquy and Driss\nLahem",authors:[{id:"108357",title:"Dr.",name:"Marc",middleName:null,surname:"Debliquy",slug:"marc-debliquy",fullName:"Marc Debliquy"},{id:"156323",title:"Dr.",name:"Driss",middleName:null,surname:"Lahem",slug:"driss-lahem",fullName:"Driss Lahem"},{id:"179585",title:"Associate Prof.",name:"André",middleName:null,surname:"Decroly",slug:"andre-decroly",fullName:"André Decroly"},{id:"179653",title:"MSc.",name:"Arnaud",middleName:null,surname:"Krumpmann",slug:"arnaud-krumpmann",fullName:"Arnaud Krumpmann"}]}],onlineFirstChaptersFilter:{topicId:"851",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,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:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,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:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:49,paginationItems:[{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81756",title:"Alteration of Cytokines Level and Oxidative Stress Parameters in COVID-19",doi:"10.5772/intechopen.104950",signatures:"Marija Petrusevska, Emilija Atanasovska, Dragica Zendelovska, Aleksandar Eftimov and Katerina Spasovska",slug:"alteration-of-cytokines-level-and-oxidative-stress-parameters-in-covid-19",totalDownloads:9,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"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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Biosensors, Biomaterials and Tissue Engineering",value:9,count:1},{group:"subseries",caption:"Bioinspired Technology and Biomechanics",value:8,count:2},{group:"subseries",caption:"Bioinformatics and Medical Informatics",value:7,count:9}],publicationYearFilters:[{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2019",value:2019,count:5},{group:"publicationYear",caption:"2018",value:2018,count:3}],authors:{paginationCount:302,paginationItems:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. 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