Active compounds and biological actions of antidiabetic herbs.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"3824",leadTitle:null,fullTitle:"HLA and Associated Important Diseases",title:"HLA and Associated Important Diseases",subtitle:null,reviewType:"peer-reviewed",abstract:'This year marks the 60th anniversary of HLA discovery by the French Nobel laureate physician Jean Dausset, as well as the 55th anniversary of the identification and naming of the first HLA. Under such circumstances, both basic HLA research and its clinical applications need a new book that comprehensively reflects the latest achievements in the field. Thus, Professor Xi as Editor has contributed to organize international experts in the areas of HLA-related basic research and clinical applications, to unite their knowledge in chapters covering various related topics, and finally to finish the book "HLA and Associated Important Diseases". 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Blood glucose is regulated by the pancreatic hormones alone or in combination with other endocrine glands and all this is controlled by one or more gene or cellular or molecular targets. If any problem occurs in the normal pathway(s), then multiple drugs or therapies are used to cure it. Moreover with the emerging technologies, multiple plant based formulations has been synthesized or in process to cure all blood glucose regulation problems and their associated diseases.
\nIt is located at the back of stomach, within left upper abdominal cavity.
\nIts parts are head, body and tail. Majority of this secretory organ consists of:
Anatomical organization of the pancreas.
Pancreas maintains blood glucose levels within a very narrow range (4–6 MM) through glucagon and insulin by their opposing and balanced actions by the phenomenon of glucose homeostasis. During sleep/between meals/when blood glucose levels are low/during prolonged fasting, α-cells release glucagon and promote hepatic glycogenolysis. Along with this, glucagon do hepatic and renal gluconeogenesis and increase endogenous blood glucose levels. In elevated exogenous glucose levels, after a meal, insulin secretion is stimulated from β-cells and after docking to its receptor on muscle and adipose tissue, insulin enables insulin-dependent uptake of glucose into tissues and lowers blood glucose levels by removing the exogenous glucose from the blood stream (Figure 2). Moreover insulin enhances glycogenesis, lipogenesis and incorporation of amino acids into proteins; thus it performs its anabolic action as compared to glucagon which is catabolic. Along with pancreas, other organs also regulate blood glucose levels (Figure 3).
\nMaintenance of blood glucose levels by glucagon and insulin.
Maintenance of blood glucose levels by different organs (a) during well fed state (b) during post-prandial state.
Genetics is identifying a whole new set of genes, proteins and pathways that are related to diabetes and blood sugar control. Till now, scientist have identified a genetic disorder in MafA (it controls the production of insulin in β-cells). Surprisingly, this genetic defect was present in an unrelated family along with diabetic and insulinoma family members. The link of this gene with a defect was detected for the first time and a stable resultant mutant protein was found with a longer life in the cell, and found to be significantly more abundant in β-cells than its normal version [2].
\nGene on chromosome-2 {encodes glucose-6-phosphatase catalytic 2 (G6PC2)} is linked with fasting glucose levels and is primarily expressed in pancreatic β-cells to convert glucose-6-phosphate back to glucose. Its genetic variation may be responsible for reduction in insulin secretion that increases glucose concentration. Chronically elevated levels of glucose may be a precursor for type 2 diabetes [3].
\n13 new genetic variants has been discovered by an international research consortium and these variants can manipulate blood glucose regulation, insulin resistance and function of insulin-secreting β-cells in European descent populations, in which 05 of the following newly discovered variants raised the risk of developing type 2 diabetes:
SNPs in the region of ADCY5 which influence fasting and postprandial glucose levels.
FADS1 which is linked with fasting glucose as well as lipid traits.
Only one variant, near IGF1 which is associated with insulin resistance
β-cell impairment, which may play a larger role in type 2 diabetes than previously recognized
Environment which may contribute to insulin resistance more than it does to insulin secretion.
By using high-density microarray analysis, more than 31,000 genes, linked with pancreas, have been discovered and main aim was to find which gen(s) were most sensitive to glucose and fatty acids particularly from the products of high fat and sugar diets. It was found that TNFR5 gene had maximum compassion to glucose and fatty acids and due to high levels of fat and sugar, beta cells are destroyed due to its over expression. These findings suggested that people with type-II diabetes, primarily with poor blood glucose management/who have not been diagnosed, are more likely to over express this gene that leads to β cell damage. But blocking of TNFR5 in beta-cells, especially when glucose and fatty acids consumption is high, halted their obliteration which shows that reticence of TNFR5 activity could be a promising treatment strategy against type 2 diabetes [4].
\nTo identify genetic variants responsible for blood sugar control, a genome-wide association study was done to find SNPs which could be correlated with Fasting Plasma Glucose levels. It was found that most strongly associated SNP was rs560887 in initial sampling of 650 non-obese French people. Same SNP was correlated with FPG levels in a secondary sample of 3400 same people, approximately 5000 Finns and a group of 860 obese French children. When results of all studied samples were combined, researchers found that each copy of T version of rs560887 leads to a 0.06 mmol/L reduction in FPG while rs560887 did not correlate with insulin levels or BMI of subjects. Moreover even after a 9 year follow-up period in French samples, this SNP also could not correlate with the risk of type 2 diabetes. Moreover two other SNPs; rs1260326 and rs1799884 (previously found to be associated with FPG) were also found to be significantly associated with FPG levels in same study and it was concluded that genes affected by these SNPs affect the threshold level of glucose in the bloodstream and triggered secretion of insulin by pancreas. When threshold will be higher, level of blood glucose increase even before insulin starts to regulate it [5].
\nThese are class B-GPCRs which are important targets for drugs of type 2 diabetes, obesity and blood glucose regulation problems. Structures of several class A-GPCRs have been solved, but class B receptors have not been well studied because of technical challenges. Their structures were identified and reported by four international research teams; NIDDK, NIGMS, FDA and NIDA. Structure of Glucagon receptor helps to understand how different domains cooperate in modulating the receptor function at molecular level. GLP-1 receptor, identified by cryo-electron microscopy, examined structure of receptor in complex with GLP-1 and its coupled G-protein while detailed structure of GLP-1 receptor, when bound by small molecules (that affect receptor’s activity) has also been given and it is difficult to expect the importance of GPCRs which are targeted by about half of all drugs. Structural information about these receptors is crucial for further drug discovery efforts [6].
\nControl of blood glucose depends heavily on G-protein-coupled receptors (GPCRs) which can span cell membranes to communicate signals from the outside to inside of cell and starts a cascade of reactions in cell when once activated by binding of a substance which had made these receptors an important target for drug development. When blood glucose drops after an overnight fast, pancreas releases glucagon which binds a GPCR, glucagon receptor, on liver and muscle cells and stimulates cells to release glucose in blood. Moreover glucagon-like peptide-1 (GLP-1) hormone works by binding to another GPCR, GLP-1 receptor, on pancreatic cells. After a meal, intestine produces GLP-1, which leads to the production of insulin from pancreas to stimulate cells to pick glucose from blood [7].
\nFor many years, heterocyclic scaffolds were the basis of anti-diabetic chemotherapies as bioactive scaffolds and have been evaluated for their biological response as inhibitors against their respective anti-diabetic molecular targets over past 5 years (2012–2017). Results revealed a diverse target sets of these scaffolds including protein tyrosine phosphatase 1 B (PTP1B), dipeptidyl peptidase-4 (DPP-4), free fatty acid receptors 1 (FFAR1), G protein-coupled receptors (GPCR), peroxisome proliferator activated receptor-γ (PPARγ), sodium glucose co-transporter-2 (SGLT2), α-glucosidase, aldose reductase, glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), glucagon receptor (GCGr) and phosphoenolpyruvate carboxykinase (PEPCK) [8].
\nIn addition to other several even newer therapies in development, Incretin- based therapies, like dipeptidyl peptidase- 4 (DPP- 4) inhibitor and glucagon like peptide-1 (GLP-1) analogues/mimetic offer a new therapeutic means for the treatment of T2DM. Moreover a great attention has been focused by many researchers on a number of potential molecular targets in adipocytes e.g. adipokines [8].
\nIn β-cells, main stimulus for insulin release increases blood glucose levels after a meal. This blood glucose is taken up by facilitative glucose transporter GLUT2 (SLC2A2) on the surface of β-cells. Once inside the cell, glucose undergoes glycolysis and an amplified ATP/ADP ratio and this distorted ratio leads to close ATP-sensitive K+-channels (KATP-channels). While in non-stimulated circumstances, these channels open to ensure the maintenance of resting potential by transporting K+-ions down their concentration gradient out of the cell. Upon closure, succeeding decrease in potency of externally moved K+-current elicits depolarization of membrane, followed by opening of voltage-dependent Ca+-channels (VDCCs). Increase in intracellular Ca+ concentrations ultimately triggers fusion of insulin-containing granules with membrane and succeeding release of their content. Whole secretory process is biphasic and 1st phase lasts for around 5 minutes after the glucose stimulus with the release of majority of insulin while in 2nd phase, which is somewhat slower, the remaining insulin is released. This insulin is stored in large dense-core vesicles which are recruited near plasma membrane immediately after stimulation so that it should be readily available. Key molecules that mediate the fusion of the insulin-containing large dense-core vesicles belong to the superfamily of the soluble
Synaptosomal-associated protein of 25 kDa (SNAP-25)
Syntaxin-1 and synaptobrevin 2 (or vesicle-associated membrane protein VAMP2)
Sec1/Munc18-like (SM) proteins, glucose vesicles form SNARE complex. To initiate fusion, synaptobrevin 2, a
Glucose-stimulated insulin release from a pancreatic β-cell.
Numerous SNARE isoforms [syntaxin-1, −3 and −4, SNAP-25 and -23, synaptobrevins 2 and 3 (VAMP2 and 3)] are involved in glucose-stimulated insulin secretion whereas VAMP 8 (a non-essential SNARE protein for glucose-stimulated insulin secretion) has its role to regulate glucagon-like peptide-1-potentiated insulin secretion. In addition to SNARE and SM proteins, a calcium sensor is required to initiate membrane fusion. Synaptotagmins (highly expressed in neurons and endocrine cells) participated in Ca2+-dependent exocytosis processes. Seventeen synaptotagmins (Syts 1–17) have been identified while only eight (Syt-1, −2, −3, −5, −6, −7, −9 and −10) are able to bind Ca2+ and form a complex with the SNAREs to smooth the progress of and activate vesicle-membrane fusion process. Only Syt-3, −5, −7, −8 and −9 are concerned with insulin exocytosis [10].
\nSeveral proteins are disturbed in the insulin signaling pathways in different conditions of insulin resistance, particularly obesity, type-II diabetes mellitus, metabolic syndrome, cardiovascular diseases, inflammatory disorders, and cancer [11].
\nIt is tetramer protein, composed of 02 extracellular α- subunits and two trans membrane β-subunits. α-subunits have a binding site to insulin while the β-subunits contain an intrinsic tyrosine kinase activity towards intracellular side. Insulin binding to α-subunit leads to conformational change and activation of β-subunit which results in tyrosyl autophosphorylation of the insulin receptor. After being activated and phosphorylated, several major and better characterized insulin signaling intracellular docking proteins {Src homology collagen (SHC), associated protein substrate (APS) and insulin receptor substrates- 1 & 2 (IRS-1 and IRS-2)} binds to insulin receptor for tyrosyl phosphorylation. All these proteins activate glucose uptake and metabolism, protein synthesis, gene expression, cell survival, growth, development, and differentiation. IRS proteins are phosphorylated on various tyrosine residues of the C-terminal region and generate specific sites for binding of proteins containing Src homoly-2 (SH2) domains [phosphatidylinositol-3 kinase (PI-3 K), Nck, and Grb-2.
\nIt is composed by a catalytic subunit (p110) and a regulatory subunit (p85) and mediate metabolic effects of the insulin. Binding of p85 subunit to phosphorylated tyrosine residues of IRS proteins activate catalytic activity of p110 subunit and subsequent rise in the generation of phosphatidylinositol 3,4-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) content. Downstream proteins from PI3 K pathway figure out several serine/threonine kinases e.g. phosphoinositide-dependent protein kinase-1 (PDK-1), protein kinase B (PKB/Akt), protein kinase C (PKC), p70 S6 kinase (p70S6 K) and glycogen synthase kinase-3 (GSK-3). All these kinases are involved in translocation of glucose transporter-4 (GLUT-4) from intracellular vesicles to plasma membrane, glycogen and protein synthesis, antiapoptotic effects and gene expression (Figure 4).
\nSignaling pathways which are involved in glucose uptake due to insulin induction starts with the recruitment of APS to activated insulin receptor and subsequent association and tyrosine phosphorylation of Cbl which interacts with Cbl associated protein (CAP) through an SH3 domain and with flotillin (a constituent of lipid raft, through a sorbin domain). Complex CrkII/C3G then binds to the phosphorylated tyrosine and residues of Cbl and activate C3G activity that exchanges GDP for GTP of TC10 (a small G-protein that belongs to the Rho family). After being activated, TC10 participates in GLUT-4 translocation (Figure 5) [12].
\nSummary of the main insulin signaling pathways. GLUT-1 and -4: Glucose transporter-1 and -4; Grb-2: Growth receptor binding-2; GSK-3: Glycogen synthase kinase-3; IR: Insulin receptor; IRS-1 and -2: Insulin receptor substrate-1 and -2; MAPK: Mitogen-activated protein kinase; PDK-1: Phosphoinositide-dependent kinase-1; PIP2: Phosphatidyl-inositol diphosphate; PI3: Phosphatidyl-inositol triphosphate; P: Phosphate; PKC: Protein kinase C; PP-1: Phosphoprotein phosphatase-1; p70S6K: Protein 70 S6 kinase; p90rsk: Protein 90 ribosomal S6 kinase; Shc: Src homology collagen; SHP-2: Phosphatase with Src homology 2 domain; SoS: Son of Sevenless.
This cascade starts with
The association of Shc to insulin receptor
Binding of Grb-2 to Shc or to IRS-1
Formation of the Grb-2/SoS (Son of Seven less) in the plasma membrane.
This complex leads to the activation of c-Ras and raf, starting the MAPK cascade. MAPK pathway is involved in insulin induced differentiation, cell growth, and development, along with some metabolic effects e.g. glycogen synthesis and GLUT-4 translocation to plasma membrane (Figure 4). However, this cascade is not enough or even required to this later effect [13].
\nIt occurs when insulin-sensitive tissues (skeletal muscle, adipose tissue and liver) cannot respond properly to hormones which cause several chronic diseases, particularly those which are linked to obesity (type-II diabetes mellitus, metabolic syndrome, dyslipidemias, cardiovascular diseases, cancer and neurodegenerative diseases). However precise mechanisms of insulin resistance are not fully understood. Following factor have been proposed to participate in its development;
\nAs free fatty acids are elevated in obesity and related illness, they are supposed to be responsible for insulin action impairment but still complete mechanisms are not known. More availability of long chain saturated fatty acids results leads to insulin resistance in liver, skeletal muscle and adipose tissue. Various hypotheses proposed to explain insulin resistance induced by saturated fatty acids [14] are;
Randle cycle
Oxidative stress
Modulation of gene transcription
Accumulation of intracellular lipid derivatives (diacylglycerol and ceramides)
Mitochondrial dysfunction
Inflammation
Chronic state of inflammation in insulin responsive tissues is major contributor to insulin resistance in obesity and related diseases. However, precise mechanisms as well as mediators involved in this interaction are not completely defined yet. Intracellular redox balance is delicately synchronized process that includes multiple generating pathways and degrading systems. Physiologically, ROS contribute in essential biological responses but their accumulation causes oxidative stress condition because of their highly oxidant nature to oxidize multiple intracellular components particularly membrane phospholipids, proteins, and DNA. In insulin resistance, increased ROS production and/or decreased ROS degradation is observed that leads to an oxidative stress condition and activation of signaling pathways related to stress. Oxidative stress is also responsible for muscle disorders and contributes to insulin resistance process. Transgenic mice expressing human ubiquitin protein E3 ligase (a protein that binds and promotes degradation of superoxide dismutase-1) leads to reduced superoxide degradation and as a result increased oxidative stress in the form of atrophy and sclerosis [15].
\nActivation of signaling pathways to stress is another reason of insulin resistance. Several serine/threonine kinases activated by oxidative stress pathways (JNK, PKC, GSK-3, NF-kB, and p38 MAPK) have been suggested to impair insulin signaling pathways [16].
\nExpression of genes involved in lipid and glucose metabolism, insulin signaling, inflammation, redox balance and mitochondrial function is modified in insulin signaling, which shows that these processes participate in the pathophysiology of insulin resistance. Disturbed mitochondrial function has been suggested to have a central role in these alterations, since this organelle participates in all these processes [17].
\nMany of the drugs have a combination of effects. If a person needs two or more treatments to manage glucose levels, insulin treatment may be necessary. Possible treatments for type 1 diabetes include [18]:
Insulin lispro (Humalog)
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Regular insulin (Humulin R and Novolin R)
Insulin isophane, also called NPH insulin (Humulin N and Novolin N)
Insulin glargine (Toujeo)
Insulin detemir (Levemir)
Insulin degludec (Tresiba)
Insulin lispro protamine and insulin lispro (Humalog Mix 50/50 and Humalog Mix 75/25)
Insulin aspart protamine and insulin aspart (NovoLog Mix 50/50 and NovoLog Mix 70/30)
NPH insulin and regular insulin (Humulin 70/30 and Novolin 70/30)
People can breathe in
Insulin human powder (Afrezza)
Amylin analogs: Pramlintide (Symlin) which mimics another hormone, amylin, that plays a role in glucose regulation.
Glucagon which can reverse blood sugar levels when they fall too low as a result of insulin treatment.
For patients with Type-II Diabetes:
Glimepiride (Amaryl)
Glipizide (Glucotrol)
Glyburide (DiaBeta, Micronase, Glynase)
The older, less common sulfonylureas are:
Chlorpropamide (Diabinese)
Tolazamide (Tolinase)
Tolbutamide (Orinase)
Today these drugs are less prescribed than in the past as they can cause hypoglycemia, leading to other health issues:
Nateglinide (Starlix)
Repaglinide (Prandin)
pioglitazone (Actos)
rosiglitazone (Avandia)
Alpha-glucosidase inhibitors
acarbose (Precose)
miglitol (Glyset)
Dipeptidyl peptidase inhibitors
alogliptin (Nesina)
linagliptin (Tradjenta)
sitagliptin (Januvia)
saxagliptin (Onglyza)
canagliflozin (Invokana)
dapagliflozin (Farxiga)
empagliflozin (Jardiance)
ertugliflozin (Steglatro)
exenatide (Byetta, Bydureon)
liraglutide (Victoza)
dulaglutide (Trulicity)
lixisenatide (Adlyxin)
semaglutide (Ozempic)
alogliptin and metformin (Kazano)
alogliptin and pioglitazone (Oseni)
glipizide and metformin (Metaglip)
glyburide and metformin (Glucovance)
linagliptin and metformin (Jentadueto)
pioglitazone and glimepiride (Duetact)
pioglitazone and metformin (Actoplus MET, Actoplus MET XR)
repaglinide and metformin (PrandiMet)
rosiglitazone and glimepiride (Avandaryl)
rosiglitazone and metformin (Avandamet)
saxagliptin and metformin (Kombiglyze XR)
sitagliptin and metformin (Janumet and Janumet XR)
They are used to treat high blood pressure to prevent or manage kidney complications of diabetes.
\nPeople can manage cardiovascular risks of diabetes (like heart disease and stroke) by taking them to lower cholesterol levels at a dozen of once per day on doctors recommendation.
\nIt is key part of diabetes management and prevention and doctors might suggest medicines to cure it without effective lifestyle measures [19]. These drugs are
There are many guide lines for each person’s health situation and each can choose best one according to their health conditions [20] e.g.
For people with type 2 diabetes and atherosclerotic cardiovascular disease (CVD), 2018 guidelines recommend following drugs as part of the antihyperglycemic treatment:
Sodium-glucose cotransporter 2 inhibitors (SGLT2)
Glucagon-like peptide 1 receptor agonists (GLP1-RA)
Type-II diabetic people with atherosclerotic CVD and heart failure or a high risk of heart failure should be prescribed with:
Sodium-glucose cotransporter 2 inhibitors
To treat people with type-II diabetes and chronic kidney disease, doctors urged to consider following guidelines to stop chronic kidney disease, CVD or both, from getting worse.:
Sodium-glucose co transporter 2 inhibitor
Glucagon-like peptide 1 receptor agonist
When medicines and lifestyle changes are not enough to manage diabetes, a less common treatment can become an option. Other treatments include different surgical procedures for treating type-I or type-II diabetes [21, 22, 23, 24, 25] which are as follows:
\nIt is also called weight-loss surgery or metabolic surgery and it help obese and type-II diabetic patients to lose a large amount of weight and regain normal blood glucose levels. Even some people with diabetes may no longer need their diabetes medicine after it. Efficacy of this surgery can be checked by the variations in blood glucose level, type of weight-loss surgery and the amount of lost weight by the patients. Moreover it can also be monitored by the time occurrence of diabetes and on duration of usage of insulin. Current research suggested that weight-loss surgery also may help to improve blood glucose control in obese type-I diabetic people but still scientists are finding long-term results of this in type-I and II diabetic patients [21].
\nNIDDK has leading role to develop artificial pancreas technology. Artificial pancreas replaces manual blood glucose levels by the shots or pumping of insulin. Single system monitors blood glucose levels throughout the patient’s life and provide insulin or a combination of insulin and glucagon routinely. The system can also be monitored remotely by parents or by medical staff. In 2016, FDA approved a type of artificial pancreas system, called a hybrid closed-loop system which tested blood glucose level after every 5 minutes throughout the day and night and automatically provided right amount of insulin to body. But when person still needed manual adjustment of insulin amount, pump delivered it at meal times. But artificial pancreas make patient free from some of daily tasks which are needed to keep blood glucose level steady or help to sleep through the night without need of wake and test blood glucose or to take medicine. Hybrid closed loop system was available in the U.S. in 2017. NIDDK has funded several important projects on different types of artificial pancreas devices for the better help of Type- I diabetic people for proper management of disease. These devices may also help type-II diabetic and gestational diabetic people to cure their disease [22, 23].
\nThis is an experimental treatment for poorly controlled type-I diabetes as in this condition immune system attacks islet cells. Pancreatic islet transplant replace shattered islets with new ones to make and release insulin. In this process, islets are donated from the pancreas of donor of pancreas and are transferred to a type 1 diabetic patient. As researchers are still doing work on pancreatic islet transplantation, so procedure is only accessible to volunteers of research studies [24, 25].
\nBioactive molecules from Natural products have been proved to improve insulin resistance and its associated complications by suppressing inflammatory signaling pathways [26]. Medicinal plants cannot be obsolete and still play a prominent role in human health care. Among natural sources, over 1200 plants have been claimed as antidiabetic remedies. While over 400 plants along with its 700 recipes and compounds have been scientifically evaluated for type-II diabetes. Metformin was developed on the basis of biguanide compound from an antidiabetic herb,
Mechanisms underlying herbal therapies using antidiabetic plants and phytocompounds. (a) Different types of medicinal herbs can be classified based on their modes of action such as insulin resistance (type 1 herbs), -cell function (type 2 herbs), and GLP-1 (type 3 herbs) and glucose (re) absorption (type 4 herbs), (b) The selected.
While more than 400 plants and compounds have shown
Active compounds and biological actions of antidiabetic herbs.
All hormones for the regulation of blood glucose levels along with their source organ up to the level of cell have been discussed in first section of chapter. Then different Pathways involved in regulating blood glucose levels in normal and abnormal conditions has been explained. Genes, Molecular and cellular targets to regulate blood glucose levels in normal and abnormal conditions has been discussed with particular focus on molecular basis of insulin signaling pathways and this pathway has been linked with Mechanism of Insulin Action and Molecular Basis of Insulin Resistance which is may be due to fatty acids, inflammation, stress and altered expression of several genes. Current scenario of Drugs and therapies to cure blood glucose regulation problems for the management of type 1 and type 2 diabetes has been explained. At the end New approaches to drug development and therapies by green synthesis to have been mentioned.
\nAll authors are highly acknowledged to the host institutions for providing a forum for the publication of this data.
\nAll authors declare that they do not have any conflict of interest with any company or organization or person.
\nAll authors are highly acknowledged to their parents and teachers who contributed their whole life for making their siblings and students a successful person.
\nMafA | musculoaponeurotic Fibrosarcoma Oncogene Family, A |
MafB | musculoaponeurotic Fibrosarcoma Oncogene Family, B |
SNPs | single Nucleotide Polymorphism |
ADCY5 | adenylate cyclase 5 |
FADS1 | fatty acid desaturase 1 |
IGF1 | insulin-Like Growth Factor 1 |
B-GPCRs | class B G protein-coupled receptors |
class A-GPCRs | class A G protein-coupled receptors |
Cbl | cannabinoid 1 |
GDP | guanosine diphosphate, |
GTP | guanosine diphosphate, |
Shc | Src homology and collagen protein |
c-Ras | rat sarcoma |
raf | rapidly Accelerated Fibrosarcoma |
JNK | c-Jun N-terminal kinase |
PKC | protein kinase C |
GSK-3 | glycogen synthase kinase-3 |
NF-kB | nuclear factor kappa-light-chain-enhancer of activated B cells |
p38 MAPK | p38 mitogen-activated protein kinases |
ACE inhibitors | acetylcholine Esterase Inhibitors |
NIDDK | National Institute of Diabetes and Digestive and Kidney Diseases |
FDA | Food and Drug Administration |
NIGMS | National Institute of General Medical Sciences |
NIDA | National Institute on Drug Abuse |
Antrochoanal polyp (ACP) is a benign, unilateral polyp originating from the maxillary sinus, extending through the natural or accessory ostia into the nasal cavity. This finding is more common in children and young adults [1] with 2:1 male to female ratio. Its etiology is vague and varies from neoplasia to inflammatory polyp or cystic degeneration of intramaxillary retention cyst. The exact anatomic origin of ACP inside the maxillary sinus is not agreed upon in the literature. The medial and posterior walls are the most common origin sites [2, 3], but the polyp may grow from virtually any site inside the maxillary sinus. ACP exits the maxillary sinus through the accessory ostium in at least 70% of cases [4], which may explain why the polyp grows inferiorly and posteriorly into the nasopharynx. Recent publications show evidence that nearly all ACPs extend through the accessory ostium [2, 5]. The most common symptoms of ACP are nasal obstruction and anterior nasal discharge, while epistaxis and pain point towards a different etiology necessitating further workup. The treatment of choice for ACP is surgical resection [1]. While different surgical techniques were described in the past, endoscopic removal of both the intranasal and intramaxillary parts of the polyp is the common practice today. ACP is common in the pediatric population. While it represents only 4–6% of all nasal polyps in adults, up to 35% of nasal polyps in children will eventually be diagnosed as ACP [6]. The common symptoms are the same as with adults, however additional sinus pathologies are rarely seen in children. Oropharyngeal descent is more prevalent in children compared with adults [7]. In addition, children generally present with more advanced disease, probably as a result of delayed diagnosis. The recurrence rate of ACP after endoscopic surgical treatment is not significantly different between children and adults [8]. A meta-analysis conducted by Galluzzi demonstrated a 15% recurrence rate in children with significantly higher rates in patients who underwent endoscopic surgical treatment alone compared with combined approach (i.e. endoscopic and trans-canine sinusoscopy or mini-Caldwell-Luc) [9].
There are different theories regarding the pathogenesis of ACP; Early studies suggested that ACP grows from an antral mucous retention cyst, a quite common finding in the general population (8–10%) [10]. In their attempt to explain why ACP occurs in only a minority of patients with retention cysts, Frosini et al. hypothesized that increased intra-sinus pressure caused by partial occlusion of the natural ostium due to inflammatory changes and edema is leading an antral cyst to herniate through the accessory ostium [5]. Histologic features of ACP, which include a high rate of inflammatory cells, may support this theory.
The association between ACP and allergy is controversial. While the exact pathogenesis of ACP is unknown, a relationship between ACP and allergic rhinitis or ipsilateral maxillary sinusitis has been shown in pediatric patients [7]. Moreover, increased recurrence rates of ACP after endoscopic surgery were noted in children who were exposed to cigarette smoke (aka ‘passive smokers’); Mantilla described a series of 27 cases of recurrent ACP in children in which nearly half of the subjects were considered as passive smokers [11]. While this data may point to a causal correlation between smoking and the development of ACP, such a relationship is not documented elsewhere and more research is needed in this area.
The diagnosis of ACP may be challenging, mainly in young children (5–8 years). In this age group, adenoid hypertrophy is a very common finding and the symptoms may resemble those of ACP, like nasal obstruction, chronic rhinorrhea and snoring. Even though the pre-operative management in these cases include nasal endoscopy and/or lateral plain films of the neck, sometimes the diagnosis of ACP may be overlooked. Another unilateral nasal pathology to be ruled out in children is foreign body but it usually manifests with unilateral foul-smelling rhinorrhea. Epistaxis is not a usual clinical feature of ACP. In these cases, vascular lesions (such as juvenile nasopharyngeal angiofibroma, hemangioma or hemangiopericytoma) and neoplasia (inverted papilloma or malignant tumors) should be excluded [12]. The key to differentiate between ACP and other pathologies is a thorough and detailed history along with meticulous physical examination. In cases of limited physical examination, imaging may contribute to the diagnosis. One should keep in mind that adenoid to nasopharynx ratio decreases with age (especially in children >8 years) due to a change in nasopharynx width [13]. Therefore, children older than 8 years must undergo complete nasal flexible endoscopy to rule out nasal polyp (Table 1).
Variable, 4–7 years | 7 years < | 7 years < | Any age (acute) 12 years < (chronic) | |
Hypertrophy of adenoid tissue | Cystic enlargement of intramaxillary polyp | Inflammatory/ allergic | Infectious (acute) inflammatory (chronic) | |
Nasal obstruction snoring chronic rhinitis | Nasal obstruction (unilateral progressive to bilateral) rhinorrhea | Rhinorrhea sneezing itching nasal obstruction ocular symptoms | Nasal obstruction rhinorrhea facial pain complications | |
Endoscopy: obstructive adnoids X-ray (lateral neck): nasopharynx obstruction | Endoscopy: unilateral nasal polyp | Endoscopy: unilateral nasal polyp | Endoscopy: edema or pus drain from middle meatus | |
Nasopharynx obstruction | Unilateral maxillary opacification choanal obstruction | Bilateral opacification of sinuses | Bilateral opacification of sinuses complication: (ring enhancement / extrasinus involvement) | |
leukotriene receptor antagonist | nasal douche, nasal steroid spray, antihistamine, leukotriene receptor antagonist, systemic steroids | nasal douche, antibiotics, nasal steroid adenoidectomy, endoscopic sinus surgery |
Differential diagnosis of pediatric nasal obstruction [14].
The most common presenting symptoms of ACP are nasal obstruction and anterior rhinorrhea. Nasal Obstruction may be unilateral or bilateral, depends on the evolution of growth of the polyp. When it emerges from the maxillary sinus ostium to the nasal cavity the patient will complain on unilateral nasal obstruction. However, as the polyp further descends into the choana it may cause bilateral obstruction, as commonly seen in hypertrophic obstructive adenoid tissue. Rhinorrhea is usually unilateral and watery; purulence is rarely seen. Other symptoms may include mouth breathing, snoring and sleep disorders, although ACP does no lead to truly obstructive sleep apnea (OSA). The cystic component is very typical to ACP. Some patients report of a sudden watery or yellow drainage followed by a relief of the nasal obstruction implying to a spontaneous rapture of the cystic part in the ACP.
Very large polyps may descend into the oropharynx and cause a foreign body sensation. As previously noted, the presentation of bilateral nasal obstruction is possible due to expansion of the polyp from one choanae to the other, however true bilateral ACP is extremely rare [15].
Computed tomography (CT) imaging with nasal endoscopy represent the gold standard in the diagnosis of ACP [5]. All patients must have preoperative sinonasal CT scan, as it is a crucial part of the diagnosis and provides critical information of nasal and sinus bony landmarks prior to surgical intervention.
The classic appearance of ACP in CT is a hypo-attenuating unilateral soft tissue mass that completely occupies the maxillary sinus. It extends through the accessory maxillary ostium into the nasal cavity, medially to the inferior turbinate with progression towards the nasopharynx (Figure 1). Less commonly, the polyp extends anteriorly to the middle turbinate and the anterior inferior turbinate region [16]. Bony changes (bone erosion, destruction or sclerosis) are not typically seen with ACP, although widening of the accessory maxillary ostium may occur, usually due to enlarging cystic portion of the polyp leading to the appearance of expansile maxillary mass (Figure 1) [8]. In cases of suspected bone destruction in CT, other pathologies such as malignancy should be considered. However, studies have shown that thinning of alveolar bone in the maxillary sinus may occur secondary to the progressive growing of ACP [2]. Lee classified 3 stages of ACP based on the radiological appearance of the lesion on CT [3, 17]: Stage I (antronasal polyp without extension to the nasopharynx), Stage II (full occlusion of the maxillary sinus ostium with extension to the nasopharynx) and Stage III (partially occlusion of the maxillary sinus ostium with polyp extension to the nasopharynx). In children, advanced CT stages (stage II, III) are more commonly seen due to delayed diagnosis in this population, as previously noted [7]. Magnetic resonance imaging (MRI) shows a hypointense T1 and enhanced T2 signals. With gadolinium administration, the cystic part of the polyp is peripherally enhanced. Although CT is the preferred imaging modality in the diagnosis of any nasal or sinus pathology including ACP, MRI may be considered in children (due to the lack of radiation exposure) and in cases of total unilateral nasal and sinus opacification in CT scans (in order to distinguish between sinus secretions and the mass itself). In nasal endoscopy, ACP appears as a gray-white colored mass with a smooth round surface. Unlike other allergic or inflammatory nasal polyps, ACP has a unique course from the maxillary sinus to the choana and has a bulging expansile behavior due to its cystic component.
Computed tomography (CT) imaging of right-sided antrochoanal polyp (ACP). (A) coronal image showing total opacification of the right maxillary sinus and nasal cavity. The antrochoanal polyp has both an intramaxillary component (
Macroscopically, ACP is composed of a cystic part filling the maxillary sinus and a solid part emerging through the maxillary ostia and filling the nasal cavity. It has a gross appearance of a “dumbbell” shape with a narrow stalk connecting between the cystic and solid components (Figure 2). Microscopically, the antral (or intra-maxillary portion) part of ACP demonstrates a central cystic cavity surrounded by a homogeneous edematous stroma with few cells [5]. The intranasal portion of the polyp is covered with a respiratory epithelium similar to the normal mucosa of the sino-nasal tract and the choanal portion occasionally shows squamous metaplasia and reactive fibrosis (Figure 3). In comparison to allergic polyp, ACP is characterized by higher inflammatory cell infiltration and edema, lower eosinophilic infiltration and less submucosal glands [18]. These findings indicate that inflammatory changes are the main pathophysiological processes in the pathogenesis of ACP while allergy plays only a minor role. In addition, the paucity of submucosal glands suggests that ACP results from edematous hypertrophy of the respiratory epithelium rather than from distention of the glandular structure, which is the event responsible for the development of ordinary nasal polyps [18]. Angiogenesis is significantly less evident in ACP compared to nasal polyps resulting from chronic rhinosinusitis, with lower expression of angiogenic markers vasculo-endothelial growth factor (VEGF) and CD-34 [12]. These findings further support the idea that ACP is a result of a local inflammatory process and could also explain why ACP has less tendency to bleed compared with other types of polyps, both as a presenting symptom or during endoscopic surgery. ACP is characterized with a significantly high prevalence of intramural cysts [19, 20]. It is speculated that these cysts may have a role in the pathogenesis of ACP, and they contribute to the gross cystic appearance of both its intramaxillary and intranasal components. Moreover, the presence of intramural cysts supports Berg’s theory [10, 20] that the cystic part of the polyp develops from obstruction in the acinar glands or lymphatic ducts secondary to persistent inflammation. The pressure generated in the process of the polyp’s growth through the accessory sinus ostium may be the cause for the substantial edema that is seen.
Combined radiologic and intraoperative views of a left-sided Antrochoanal polyp. (A) & (B). Coronal and axial images showing total opacification of the left maxillary sinus and nasal cavity. The intra-maxillary portion
Typical histologic characteristics of ACP. Image (A) shows a cystic portion of ACP with cuboidal epithelium (H&E original magnification X200). Image (B) demonstrate the intranasal portion of the ACP, edema is seen (H&E X100). Images (C) & (D) demonstrate squamous metaplasia of choanal portion of the ACP (C- H&E X200, (D)- monoclonal P63 antibody stain x200).
An explanation of why ACP presents with more cystic changes than diffuse chronic rhinosinusitis with nasal polyps (d-CRS) may be related to their different origins. ACPs develop from the maxillary sinus, characterized by typical respiratory epithelium with thin lamina propria, cyst formation and fewer submucosal glands. On the contrary, nasal polyps in d-CRS typically originate from the ethmoid sinus, which has a thick submucosal layer [21].
When comparing ACP with d-CRS preparations, Warman et al. found that ACP exhibits typical histologic features like cyst formation and edema. ACP demonstrated significantly increased edema when compared to the d-CRS (82.5% vs. 44.4% respectively, p < 0.001), and higher cyst formation (40% vs. 6.2% P = 0.02). More over ACP preparations demonstrate lower degrees of inflammatory markers than d-CRS [22]. The lack of an inflammatory drive in the pathogenesis of ACP may explain why anti-inflammatory treatment is futile in this population, leading to the common notion that ACP is a rather surgical issue than a medical one.
Surgery is the standard of care in the treatment for ACP. Since its first description by Killian in 1906, many surgical techniques have been proposed for exposing the maxillary region [4]. Successful ACP resection depends on complete removal of the intramaxillary component of the polyp. The ideal procedure should facilitate excellent approach to all maxillary sinus walls and yet be minimally invasive as possible, especially in children. Currently, various surgical approaches are available: endoscopic sinus surgery (ESS) with polyp removal via either inferior meatus or middle meatus, or a combined inferior and middle meatal naso-antral window. Other options such as ESS with adjuvant canine fossa puncture, or ESS with “mini Caldwel-Luc” procedure aim to facilitate visualization of the anterior and inferior walls of the maxillary sinus [4, 23, 24].
Described by Mikulicz in 1887, inferior meatal antrostomy (known as intranasal antrostomy) was a common surgical procedure in the management of maxillary sinus disease. However, the popularity of this technique has declined with the increased use of middle meatal antrostomy due to the growing recognition that an opening in the inferior meatus does not improve sinus drainage, and might even harm the maxillary sinus mucociliary clearance mechanism. Nevertheless, endoscopic approach via inferior meatal antrostomy has the advantage of inferior meatal naso-antral window that avoids violation of the ostiomeatal complex (OMC) and provides better access to anterior-inferior maxillary sinus lesions. Arguments against inferior meatal antrostomy include: persistent sinus disease following surgery, low patency rates, possible injury to the nasolacrimal duct or to developing canine teeth, and technical difficulties associated with the procedure [24, 25]. While these arguments were substantial using anterior rhinoscopy approach, they are not valid with endoscopic approach in EIMA. As the inferior turbinate is carefully medialized, the opening of the nasolacrimal duct (Hasner’s valve) is clearly seen and preserved. Then, the maxillary wall is penetrated posterior to that point, and an antrostomy of 8–10 mm is created. Once a satisfactory exposure is achieved, view of the posterior, lateral and anterior portions of the sinus walls is possible with 0- and 45-degree endoscope in respect. The lesion is then removed with straight and curved instruments. At the end of the procedure, the inferior turbinate is lateralized back to its original position [24, 25].
Landsberg and Warman reported 56 patients with multiple maxillary pathologies (45% of them with ACP) in which EIMA was the primary approach for revision surgery. In a follow-up period for at least a year, 93% of patients had no evident sinus disease recurrence. There were no cases of ACP recurrence, and recirculation was not observed during the follow-up period. In addition, no major complications such as nasolacrimal duct injury or bleeding were observed [24].
Endoscopic sinus antrostomy via the middle meatus (EMMA) is currently considered the gold standard treatment for ACP resection. It is generally recommended that the antral portion should be completely removed together with its stalk to minimize polyp regrowth. As a result, the intranasal and choanal components of the polyp should be resected first (Figure 2). Occasionally when the choanal portion is too large, it is easier to push it back to the oropharynx and remove it trans-orally.
Next, the cystic part of the polyp is resected through maxillary antrostomy. The maxillary sinus natural ostium is identified and usually connected with the already enlarged accessory ostium. Resecting the intramaxillary portion includes −45°-70°- endoscopes to better visualize and identify the origin of the polyp. Removal of this intramaxillary portion is extremely important as to minimize post-operative recurrence [4, 26, 27].
Recurrence rate after EMMA is low. Cook et al. observed no recurrence in 33 patients with ACP [28]. Sometimes the intramaxillary portion is tightly adherent to the anterior or antero-inferior walls of the sinus, which makes the dissection a challenging task. In these cases, usage of angled instrumentation is strongly recommended. Nevertheless, the recurrence rate in these cases may increase up to 20% [17, 24, 26, 27].
Ozer et al. reviewed 42 patients who underwent ESS for ACP removal. Transcanine sinoscopy and Caldwell Luc approach were used in addition in 14 and 13 patients respectively. They found recurrence in 3/15 patients after ESS alone (20%), yet there was no recurrence after combined ESS and transcanine sinoscopy or the Caldwell Luc approach [29]. They postulated that the relative high recurrence rate may be due to improper identification of the attachment site of the polyp inside the maxillary sinus (50% of all cases). As a result, they advised considering combined approaches in cases when the attachment site is not clearly recognized. Hong et al. recommended powered instrumentation (Hummer, Stryker Instruments, Kalamazoo, MI) during ESS as an effective technique for removing ACP, especially the antral portion. They found an improvement rate of 96.4% with no significant complications when powered instrumentation was used [29, 30]. Complications following ACP resection are rare.
Lee and Huang used the transnasal endoscopic approach for ACPs originated from the inferior and posterior walls of the maxillary sinus, saving the more invasive combined endoscopic and transcanine approach for polyps originated from the lateral wall or in revision surgery. They reported success rate of the transnasal endoscopic approach and the combined endoscopic middle meatal and transcanine approach as 76.9% and 100%, respectively [31].
As mentioned earlier, Ozer et al. found no recurrence after combined ESS and transcanine sinoscopy approach [29].
Transcanine exposure has some complications such as facial swelling pain and rarely injury to the infraorbital nerve. Although rare these complications yet are against using transcanine procedure in ACP resection, especially if the polyp is approachable via EIMA.
Kelles et al. retrospectively reviewed 46 patients treated for ACP during a 7-year period. 20 patients underwent endoscopic endonasal surgery (ESS) with mini-Caldwell operation (performing a canine fossa window of 0.5–0.6 cm), while 26 patients underwent ESS alone. The only statistically significant difference between the groups was the recurrence rate, which was higher in the ESS group compared with ESS plus mini-Caldwell group (P < 0.05).
In the ESS group, bleeding, synechia, and ostium stenosis were more evident than in the ESS plus mini-Caldwell group, but these differences were not statistically significant. Therefore, Kelles theorized that adding the mini Caldewell-Luc approach allowed better visualization of the maxillary sinus walls and subsequently easier resection of the remnant polyp [23].
Atighechi et al. used a mini-Caldwell approach with ESS in their patients. They reported minimal recurrence and low complication rates, deciding that the technique is useful for the completely removal of ACP [32].
The traditional Caldwell-Luc approach offers good exposure and ensures complete removal of the polyp with the associated antral mucosa. Nevertheless, this approach has been largely abandoned in the treatment of maxillary sinus pathologies, because it does not address the natural ostium of the maxillary hence considered non-functional. Complications include: cheek anesthesia, sensory deficits, cheek swelling and risks for normal teeth development in children [4, 23, 29, 33, 34].
As previously noted, the incidence of ACP is higher in children and young adults. Although no difference in the pathophysiology or histology were seen between children and adults, children are at higher risk for recurrence. It is reasonable to believe that the anatomically narrow sinuses, the not-yet erupted teeth, and concern of maxillary growth may affect the surgeon’s decision regarding the surgical approach, leading to higher failure rate [17, 31, 35].
In his review of 200 patients with ACP, Forsini described recurrence in 4 patients (2%) all of which were children <7 years of age, in whom only polypectomy was performed. Eventually, in all cases of recurrence ESS was performed without evidence of recurrence [4].
As evident by various published series, recurrence rates range from 0% reported by Tsukidate to 64% reported by Saito and collaborators. Recurrence rates vary between different surgical approaches, patient’s age and other factors such as accompanying sinus pathologies [36, 37]. This raises the question – how long should we follow patients ACP resection?
Lee and Huang determined that 65% of their pediatric patients with ACPs had associated chronic sinusitis. Similarly, some authors have also identified association of ACPs with allergic disease. The main hypothesis is the challenge of removing the entire sick mucosa with the origin of the polyp once there is chronic inflammation [31]. Natasha Choudhury reported 29 patients after EMMA surgery for ACP. They described no polyp recurrence, with a mean follow-up period of 14.7 months [8]. Galluzzi reviewed 13 studies and found that recurrence in children is higher than in adults, mostly because of reasons described earlier. The review showed that combined approach had the lowest recurrence rate, with a range of follow-up between 6 to 120 months. Most recurrences were noted between 5 months to 3 years after initial surgery [17]. Some authors claim that different anatomic variations in the nasal cavity such as septal deviation, conchal hypertrophy, and concha bullosa may increase the intramaxillary pressure, hence predisposing for the development of ACP. While these variations were documented in up to 80% of patients with ACP, none of them were linked to increased rates of recurrence [4, 17, 23, 24, 30]. In most relevant studies, the time of recurrence was 1.2 ± 0.6 years. Therefore, it is advised to monitor ACP patients for at least 2 years after surgery in order to detect 95% of recurrent cases [35].
ACP originates in the maxillary sinus of children and young adults. Its etiology is speculative, currently considered a benign cystic polyp with limited inflammatory characteristics. It has a consistent three component structure intramaxillary, intranasal and choanal portions. ACP has a typical imaging characteristic and the gold standard of treatment is complete surgical resection. Special attention should be given to identify and resect the intramaxillary portion to prevent recurrence. Long term follow-up is needed to rule out polyp regrowth.
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Genomics studies of large populations are producing a huge amount of data, giving rise to computational issues around the storage, transfer, and analysis of the data. Fortunately, cloud computing has recently emerged as a viable option to quickly and easily acquire the computational resources for large-scale NGS data analyses. Some cloud-based applications and resources have been developed specifically to address the computational challenges of working with very large volumes of data generated by NGS technology. 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Using Salsa20/12 stream cipher, the texture images can be encrypted using bit masking and permutation procedures and as part of a new scheme for encrypting 3D objects, which complements the existing methods for 3D object encryption. 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Advances in these systems follow different approaches, such as the integration of new protocols and standards, combination with artificial intelligence algorithms, application of big data processing methodologies, among others. These new systems and applications also should face different challenges when applying this kind of technology into health areas, such as the management of personal data sensed, integration with electronic health records, make sensing devices comfortable to wear, and achieve an accurate acquisition of the sensed data. 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We report on the level of student engagement and the extent to which learning outcomes were met through the introduction of such an activity.",book:{id:"11552",title:"Gamification - Analysis, Design and Development",coverURL:"https://cdn.intechopen.com/books/images_new/11552.jpg"},signatures:"Mike Mavromihales and Violeta Holmes"},{id:"82656",title:"Application of Genetic Algorithm in Numerous Scientific Fields",slug:"application-of-genetic-algorithm-in-numerous-scientific-fields",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105740",abstract:"The genetic algorithm (GA) and its variants have been used in a wide variety of fields by the scientists efficiently for solving problems. From the pool of evolutionary algorithms, the GA is chosen by the researchers and has been popular as a useful and effective optimizer. It has several advantages and disadvantages. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"11",type:"subseries",title:"Cell Physiology",keywords:"Neurodevelopment and Neurodevelopmental Disease, Free Radicals, Tumor Metastasis, Antioxidants, Essential Fatty Acids, Melatonin, Lipid Peroxidation Products and Aging Physiology",scope:"\r\n\tThe integration of tissues and organs throughout the mammalian body, as well as the expression, structure, and function of molecular and cellular components, is essential for modern physiology. The following concerns will be addressed in this Cell Physiology subject, which will consider all organ systems (e.g., brain, heart, lung, liver; gut, kidney, eye) and their interactions: (1) Neurodevelopment and Neurodevelopmental Disease (2) Free Radicals (3) Tumor Metastasis (4) Antioxidants (5) Essential Fatty Acids (6) Melatonin and (7) Lipid Peroxidation Products and Aging Physiology.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11407,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null,series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević",profilePictureURL:"https://mts.intechopen.com/storage/users/186048/images/5818_n.jpg",institutionString:null,institution:{name:"University of Osijek",institutionURL:null,country:{name:"Croatia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria",profilePictureURL:"https://mts.intechopen.com/storage/users/79615/images/system/79615.png",institutionString:null,institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}},{id:"84459",title:"Prof.",name:"Valerie",middleName:null,surname:"Chappe",slug:"valerie-chappe",fullName:"Valerie Chappe",profilePictureURL:"https://mts.intechopen.com/storage/users/84459/images/system/84459.jpg",institutionString:null,institution:{name:"Dalhousie University",institutionURL:null,country:{name:"Canada"}}}]},onlineFirstChapters:{paginationCount:3,paginationItems:[{id:"82956",title:"Potential Substitutes of Antibiotics for Swine and Poultry Production",doi:"10.5772/intechopen.106081",signatures:"Ho Trung Thong, Le Nu Anh Thu and Ho Viet Duc",slug:"potential-substitutes-of-antibiotics-for-swine-and-poultry-production",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Antibiotics and Probiotics in Animal Food - Impact and Regulation",coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",subseries:{id:"20",title:"Animal Nutrition"}}},{id:"82905",title:"A Review of Application Strategies and Efficacy of Probiotics in Pet Food",doi:"10.5772/intechopen.105829",signatures:"Heather Acuff and Charles G. 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