\r\n\tDigital images can be easily distorted by noise during the acquisition, processing, and transmission. Noise level is an important parameter to consider in image processing algorithms, including denoising, compression, feature extraction, motion estimation, optical flow, segmentation, super-resolution, and image quality assessment. Their performance depends on the accuracy of the noise level estimate.
\r\n
\r\n\tImage denoising is an important stage to improve the accuracy of many image processing techniques, such as image segmentation and recognition. Image segmentation is another important stage in computer vision applications. Many methodologies utilize both stages in a unique algorithm to solve the problem of the segmentation of noisy images to provide better classification and recognition compared to algorithms that independently use these two stages. \r\n\tThe goal of this book will be to collect original research chapters that develop or apply new theories and/or hardware or software to process the acquired noisy images to solve the problem of Segmentation of noisy images in the field of medical imaging, remote sensing, engineering, and other research applications.
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1. Introduction
Tryptophan (TRP) is one of the essential amino acids, which must be taken as food. It is not only needed for protein synthesis but serves as a substrate for bioactive component with important physiological roles.
There are three pathways in TRP metabolism: serotonin (5-HT), kynurenine (KYN), and indole-3-acetic acid pathways.
Since 5-HT is known as an important neurotransmitter and derived from TRP, many people know about TRP to some extent. 5-HT is really involved in the adaptive responses in the central nervous system and considered to be related to mood, anxiety, or cognition [1].
5-HT is further converted in the pineal body and the retina to N-acetyl serotonin (NAS) and melatonin which controls circadian rhythm [2].
In mammals, most of the free TRP is converted to KYN and generates metabolites involved in inflammatory, immune, responses, and neurotransmission [3].
We have recently succeeded in simultaneous measurements of almost all TRP metabolites including melatonin by using an ultrahigh speed liquid chrom`atography and mass spectrometry (LC-MS) [4], which is the first time in the world.
In this chapter, we report about the precise methodology of the simultaneous measurements and some results obtained from stressed rats and depressive patients.
1.1. Measurements of TRP metabolites using LC-MS
1.1.1. Background
Since 5-HT and its derivatives have the strong fluorescence, high-sensitive analyses of some TRP metabolites can be performed by liquid chromatography with fluorescence detection. However, it is very limited to analyze the total metabolites including kynurenine by photometric detection although kynurenic acid (KYNA) can be detected as zinc chelate compound under zinc acetate solution.
In the past years, liquid chromatograph mass spectrometry (LC-MS) has been widely spread in many areas including clinical and biological analyses. Since LC-MS with electrospray ionization (ESI) is suitable for determination of metabolites of TRP, LC-MS is expected as a powerful tool for this type of analysis.
In addition, the tandem mass spectrometer also has widely used in recent years with its high sensitivity and selectivity.
There are several researches for the simultaneous analyses of TRP metabolites using LC-MS or LC-MS/MS methods for clinical samples such as human serum and plasma [5, 6]. In general, isotope-labeled internal standards are used in LC-MS/MS analysis to improve the accuracy, although isotope-labeled regents are expensive and limited availability [7, 8]. Even though less accurate, acceptable results can be obtained without internal standards for the screening purposes. In this chapter, the simultaneous determination of TRP metabolites in human plasma by LC-MS/MS technique combined with simple pretreatment procedure is described.
1.1.2. Regents and instrumentation
The simultaneous analytical method was developed for major metabolites of TRP including melatonin.
The targets are 17 of major metabolites, tryptophan (TRP), L-5-hydroxytryptophan (5-HTP), serotonin (5-HT), kynurenine (KYN), 5-hydroxy-tryptophol, tryptophol, 5-hydroxyindoleacetic acid (5-HIAA), indole-3-acetic acid, anthranilic acid (AA), kynurenic acid (KYNA), quinaldic acid, 3-indolebutyric acid, 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HAA), xanthurenic acid (XA), melatonin, and quinolinic acid (QA). Each compound is commercially available from major chemical regent manufacturers, such as Fujifilm-Wako chemical (Osaka, Japan) and Sigma-Aldrich (St. Louis, MO, USA).
Analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 mass spectrometer equipped with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan).
The targets are separated by reversed phase mode using ODS analytical column, L-Columns ODS (2.1 mm x 150 mm, CERI, Tokyo, Japan) with a gradient elution. Mobile phases were 0.1% formic acid solution and acetonitrile with 5% concentration of acetonitrile to 3 min, then 5–95% in 6 min followed by 5% in 3 min (12 min analytical cycle) at total flow rate of 0.4 mL/min. The temperature of the column was 40°C. For LC-MS, electrospray ionization (ESI) was used with multi-reaction monitoring (MRM) mode.
Flow rate of the neutralizer and the drying gas were 2 L/min and 10 mL/min, respectively. The temperature of desolvation line (heated capitally tube) was 250°C. ESI interface was used at 400°C with 10 L/min of heating gas flow. Each MRM transition was optimized using each standard solution. Optimized results are shown in Table 1.
Qualification (m/z)
Qualification (m/z)
Compound
Molecular weight
Monoisotopic mass
Precursorion
Production
Precursorion
Production
DL-Trypotophan
204.225
204.090
205.10
188.10
205.10
146.10
L-5-Hydroxytrypotophan
220.225
220.085
221.10
204.05
221.10
162.00
Serotonin
176.215
176.095
177.10
160.10
177.10
115.05
L-Kynurenine
208.214
208.085
209.10
192.00
209.10
94.05
5-Hydroxytrypotophol
177.200
177.079
178.10
160.10
178.10
115.05
Trypotophol
161.200
161.084
162.10
144.05
162.10
117.10
5-Hydroxyindole -3-acetic acid
190.176
190.051
192.10
146.05
192.10
110.00
Indole-3-acetic acid
175.184
175.063
176.10
130.05
176.10
77.05
Anthranilic acid
136.129
136.040
138.10
120.05
138.10
65.05
Kynurenic acid
189.167
189.043
190.10
144.05
190.10
89.10
Quinaldic acid
172.161
172.040
174.10
128.05
174.10
156.05
Indole-3-acetic acid
202.230
202.087
204.10
186.10
204.10
130.10
3-Hydroxykynurenine
224.213
224.080
225.15
208.20
225.15
162.15
Hydroxyanthranilic acid
152.128
152.035
154.15
136.20
154.15
80.15
Xanthurenic acid
205.167
205.038
206.15
160.20
206.15
132.20
Melatonin
232.279
232.121
232.20
174.10
232.20
130.05
Quinolinic acid
167.120
167.022
168.00
78.10
168.00
150.00
Table 1.
MRM transition.
All mother solution of 1 mg/mL had been stocked under −80°C and standard samples for calibration curve were prepared before use as mixture solution by consideration of each range of measurement concentration.
1.1.3. Analysis of human plasma
Aliquot of 50 μL human plasma was used for each sample analysis. The procedure including deproteinization is shown in Figure 1. The typical chromatograms of 17 major metabolites are shown in Figure 2 as standard solution and in Figure 3 as human plasma sample. These chromatograms demonstrate the usefulness of the developed method for simultaneous analysis of TRP metabolites.
Figure 1.
The procedure of deproteinization.
Figure 2.
Chromatograms of 17 major metabolites of tryptophan.
Figure 3.
Chromatogram of human plasma sample.
1.2. Stress and TRP metabolism
Stress influences many functions related to mental and body health. We have shown that the application of electric shock increased plasma and brain TRP, 5-HT, and 5-HIAA levels [9, 10] and changed nicotine-induced release of 5-HT or dopamine in rats [11, 12, 13, 14]. We also examined changes in serotonergic and kynurenic pathways in rats exposed to foot shock [15].
Stress induces a number of changes in the central system of neurotransmitters, particularly noradrenaline and 5-HT [16, 17].
A pathologic overabundance of endogenous excitotoxin, quinolinic acid, or hypofunction of KYNA has been hypothetically linked to the occurrence of seizures and nerve cell death [18, 19].
1.2.1. Stress and TRP metabolites in the brain
Animals: Male Wistar rats (9 weeks old) were fed with standard laboratory foods and tap water ad libitum. Two weeks later, rats were randomly divided into two groups. One group received foot shock, which was given as a series of 10-s shock (o.19 mA) followed by 50 s intervals during a 60-min period. CT 110 cycle timer and NS-SG01 shock generator scrambler (Neuroscience Inc., Tokyo, Japan) were used. Samples of 10 rats were taken immediately after the foot shock and samples of another 10 rats were taken 24 h after the shock. Ten rats were used as controls.
Blood: Rats were anesthetized with pentobarbital, and blood was taken by heart puncture and put into a tube containing 3/13% sodium citrate. Plasma was obtained by centrifugation at 3000 rpm for 20 min.
Brain sampling: The brains were removed and chilled on ice. Eight regions (cerebellum, medulla, hypothalamus, striatum, midbrain, hippocampus, cortex, and frontal cortex) were dissected and samples were immediately frozen. Frozen brain samples were homogenized in 0.15 N perchloric acid containing 0.025% EDTA (pH 3.0). The samples were centrifuged at 14,000 rpm for 20 min at 4°C. After centrifugation, the supernatant was filtered (0.45 μm Millipore filter) and stored at −80°C until assayed.
Figure 5 shows that 5-HT levels increased significantly at hypothalamus and midbrain soon after the shock but returned normal 24 h later.
5-HT levels were not increased in cerebellum, medulla, striatum, hippocampus, cortex, and frontal cortex.
Figure 6 shows 5-HIAA levels of various brain areas after foot shock.
5-HIAA levels significantly increased in all the brain areas except striatum but returned normal 24 h later.
Figure 7 shows KYN levels in various brain areas after foot shock.
KYN levels significantly increased in all the brain areas after foot shock but returned to normal 24 h later.
Figure 8 shows plasma levels of TRP, 5-HT and 5-HIAA after foot shock.
Plasma levels of TRP, 5-HT, and 5-HIAA significantly increased after foot shock but returned to normal 24 h later.
Figure 9 shows plasma levels of KYN,3-HKYN, and KYNA after foot shock.
Plasma levels of KYN, 3-HKYN, and KYNA increased significantly after foot shock but returned to normal 24 h later.
1.3. TRP metabolites in plasma of patients of depression
We asked male and female acquaintances older than 50 years old and male and female college students to participate in the experiments. We checked their health carefully and recruited them if there were no health problems such as diabetes, hypertension, or no serious diseases experienced in the past. They did not smoke in the past. We also excluded people who took drugs for dyslipidemia, hyperglycemia, or hypertension. We collected blood samples early morning. Participants were asked not to eat anything after 21.00 PM the previous evening. Plasma specimens were collected for assays of blood parameters. We obtained an informed consent prior to conducting the protocol which had been approved by the Ethical Committee of Showa Women’s University and Yokohama North Hospital of Showa University.
Patients were diagnosed to be monopolar depression at the psychiatry clinic of Yokohama North Hospital of Showa University. The Zung Self-Rating Depression Scale [20] was used, which is a short self-administered survey to quantify the depressed status of a patient. There are 20 items on the scale that rate the affective, psychological, and somatic symptoms associated with depression. We took blood from five male patients (26, 30, 45, 47, and 56 years old) and four female patients (23, 25, 41, and 60 years old).
5-HT was detected only in plasma of two patients. Both of them were young females. A 60-year-old woman took Jay Zoloft 25 mg and ethyl loflazepate 1 mg, and another 41-year-old woman took Cymbalta 20 mg and Luran 3 mg. 5-HT was not detected in plasmas of these women.
The number of healthy old men and young women were 20, and the number of depressive patients were 9.
Tables 2 and 3 show the background data of these patients.
Figure 10 shows plasma levels of 5-HT of healthy young women, old men and depressive patients.
Plasma levels of 5-HT in depressive patients were very low compared to those of old men and young women. 5-HT was detected in plasmas of only two young females.
Although 5-HT/TRP ratio of depressive patients was low compared to that of old men and young women, 5-HIAA/TRP ratio was almost the same as that of old men and young women.
Figure 12 shows that there were no differences in KYN/TRP ratios between that of old men, young women, and depressive patients.
2. Discussion
As stated above, most of the metabolites of KYN pathway are found in the brain [1, 21, 22, 23]. Some metabolites of KYN pathway are neurotoxic and some are neuroprotective.
KYNA is an endogenous neuroprotective agent that is usually present in the brain at nanomolar concentration [24]. KYNA is an antagonist to quinolinic acid (QA) and acts on the glycine modulatory site of the NMDA receptor at low concentration [22] and at higher concentration at the glutamate site of the NMDA receptors and also on the a-amino3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors [25]. It also antagonizes the alpha 7 nicotinic acetylcholine receptors [26] and selectively activates a G-protein-coupled receptor, GPR35–48 [27]. Many neuroactive intermediates are shown in KYN pathways [28]. So, we decided to measure some of TRP metabolites in the brain and plasma in the stressed rats.
Our results show that 5-HT levels increased only in hypothalamus and midbrain, but its degradation product, 5-HIAA levels, increased in every part of the brain. These results may imply that 5-HT is quickly converted to 5-HIAA soon after shock, so that 5-HT levels apparently did not increase after shock. This finding is important in the explanation of plasma 5-HT and 5-HIAA levels in patients of depression.
Some of TRP metabolites were shown to be neuroexcitatory and convulsive, thus toxic [29]. One of such neuroexcitatory factors in KYN pathway is 3-HKYN [24]. Its synthesis is catalyzed by kynurenine 3-hydroxylase. Although data of brain analyses were not shown here, 3-HKYN levels increased in all the brain areas and plasma (Figure 6).
3-HKYN is said to be the most toxic substance in TRP metabolism [30]. So stress induces disturbances in the central nervous system by increasing levels of 3-HKYN (Figures 4, 5, 6, 7, 8, 9).
Figure 4.
TRP pathways.
Figure 5.
Serotonin (5-HT) levels in various brain areas after electric foot shock. con, control; E0, soon after the shock; E1, 24 h after the shock. *p < 0.05 and **p < 0.01.
Figure 6.
5-HIAA levels in various brain areas after foot shock. con, control; E0, soon after the shock; E1, 24 h after the shock. *p < 0.05.
Figure 7.
Kynurenine levels in various brain areas after foot shock. con, control; E0, soon after the shock; E1, 24 h after the shock. **p < 0.01 and ***p < 0.001.
Figure 8.
Plasma levels of TRP, 5-HT, and 5-HIAA after electric foot shock. con, control; E0, soon after the shock; E1, 24 h after the shock. *p < 0.05 and **p < 0.01.
Figure 9.
Plasma levels of KYN (kynurenine), 3-HKYN (3-hydroxykynurenine), and KYNA (kynurenic acid). con, control; E0, soon after the shock; E1, 24 h after the shock. **p < 0.01 and ***p < 0.001.
KYN is usually hydroxylated to 3-HKYN and then further converted to 3-hydroxyanthranilic acid (3-HAA). 3-HAA is rapidly converted to QN by the non-enzymatic reaction and further to NAD+.
The other pathway of KYN, the production of KYNA and xanthurenic acid (XA), is minor under normal conditions. KYNA is an endogenous antagonist of excitatory amino acid receptors and may serve as a modulator of excitatory nerve transmission. This study may suggest that stress induces the indirect modulation of excitatory amino acids in the central nervous system by increasing KYNA.
KYNA has an antagonist activity of the three ionotropic excitatory amino acid receptors [22, 31]. At low concentrations, KYNA blocks the glycine co-agonist site of N-methyl-D-aspartate receptor and may serve to prevent the overactivation of glutamic acid receptor. When brain kynurenic acid levels were increased experimentally, neuroprotection and seizure reduction have been reported [32].
The roles of various metabolites of KYN pathway are reviewed [28], so we do not discuss these roles in detail.
As to relationships between serotonin levels and depression, we analyzed plasma levels of TRP metabolites in patients of depression.
Although the concentration of 5-HT has been considered to be low in depressive patients [33], 5-HT concentration in the brains of suicide victims was not low [34]. Therefore, it is not known if 5-HT concentration is decreased in the brains of depressive patients (Table 2).
Young men (n = 20)
Young women (n = 20)
Old men (n = 20)
Age
20.7 ± 1.5
21.2 ± 0.7
60.8 ± 9.9
Height (m)
1.72 ± 0.06
1.58 ± 0.05
1.69 ± 0.07
Weight (kg)
65.1 ± 8.9
51.4 ± 5.8
71.1 ± 13.1
BMI
22.1 ± 3.1
20.4 ± 1.6
24.9 ± 3.7
Table 2.
Basic backgrounds of healthy participants.
We decided to measure TRP metabolites in patients of monopolar depression. Table 3 shows five male patients participated in the experiments. The age is 44–61 years old (41.2 ± 11.3). Plasma serotonin levels were detected only in two young female patients. We could not measure 5-HT in plasma in seven persons, which is shown in Figure 10.
Patients
Sex
Serotonin detection
Visit (age)
Medication
H1
Male
—
45
None
H2
Male
—
47
None
H3
Female
—
60
Jay Zoloft 25 mg, ethyl loflazepate1 mg
H4
Female
+
23
None
H5
Female
+
25
None
H6
Male
—
30
None
H7
Female
—
41
Cymbalta 20 mg, Luran 3 mg
H8
Male
—
56
None
H9
Male
—
26
None
Table 3.
Various parameters of patients.
Figure 10.
5-HT levels in plasmas of depressive patients and controls.
Although plasma serotonin levels and 5-HT/TRP ratio were low in depressive patients, the levels of 5-HIAA/TRP were not lower in depressive patients. This result indicates that 5-HT is degraded to 5-HIAA in depressive patients almost to the same extent to healthy old and young women (Figures 11 and 12).
Figure 11.
5-HT or 5-HIAA/TRP ratio.
Figure 12.
KYN/TRP ratio.
We measured the levels of KYN in healthy old men and young women and depressive patients. TRP seems to be degraded to KYN pathways to the same extent in these three groups.
These results suggest that in depressive patients 5-HT was quickly degraded to 5-HIAA, and this seems to be a reason of low 5-HT levels in depressive patients.
As to a relationship between serotonin pathway and KYN pathway, Lapin IP suggested that in depression tryptophan 2,3-dioxygenase in the liver shunted metabolism of serotonin away from 5-HT production to KYN production, resulting in serotonin deficiency [35]. KYN, QN, and 3-HKYN were shown to be anxiogenic and KYNA were anxiolytic [36]. From these results, he tried to explain the effects of antidepressive drugs.
Our results do not support this hypothesis. Metabolites of KYN pathways were not high in depressive patients.
There have not been enough studies as to 5-HT levels in the brain of patients of bipolar depression. Serotonin levels in cerebrospinal fluids of patients of bipolar depression were shown to be high [37] or normal [38]. So it seems to be very important to discriminate monopolar and bipolar depression to study roles of serotonin in the pathogenesis of disease.
Our results show that plasma 5-HT levels were low and metabolites of KYN pathway were not changed in patients of monopolar depression.
3. Statistics
Standard ANOVA methodology was used and p < 0.05 was considered as significant difference. Results are expressed as mean ± SD. Bars of figures represent standard deviations.
4. Ethics
This work has been approved by the Ethical committees of Showa Women’s University, Showa University School of Medicine, and NPO “International projects on food and health” and has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments.
Acknowledgments
Experiments were designed and performed by all of the authors. AT wrote the manuscript. Statistical analyses were done by FS. All authors read the manuscript and approve the final manuscript. All the authors had responsibilities for a final content. A part of the work was reported in Japanese (http://www5c.biglobe.ne.jp/~takada-a/protein%20and%20brain.pdf).
\n',keywords:"tryptophan, serotonin, 5-hydroxyindole acetic acid, kynurenine, 3-hydroxykynurenine, kynurenic acid",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/62436.pdf",chapterXML:"https://mts.intechopen.com/source/xml/62436.xml",downloadPdfUrl:"/chapter/pdf-download/62436",previewPdfUrl:"/chapter/pdf-preview/62436",totalDownloads:1045,totalViews:397,totalCrossrefCites:1,dateSubmitted:"March 1st 2018",dateReviewed:"May 9th 2018",datePrePublished:"November 5th 2018",datePublished:"November 21st 2018",dateFinished:"July 3rd 2018",readingETA:"0",abstract:"There are three pathways in tryptophan (TRP) metabolism. Serotonin (5-hydroxytryptamine; 5-HT) pathway is important in mood, anxiety, memory, and cognition and is impaired in depression. Kynurenine (KYN) pathways are involved in immunity, inflammation, muscles movement, and mental health. We investigated changes in TRP metabolites in plasmas of stressed rats and in depressive patients. TRP metabolite levels in 5-HT and KYN pathways in various brain areas and plasma were increased soon after electric foot shock given to rats but returned to normal 24 h later. Plasma levels of 5-HT were very low or undetectable in patients of monopolar depression. 5-hydroxyindole acetic acid (5-HIAA)/TRP ratios or KYN/TRP ratios were not different between healthy controls and depressive patients, indicating 5-HT quickly being degraded into 5-HIAA in patients of depression but KYN levels were not changed in depression. These results indicate that TRP metabolism changes upon stress application and in patients of depression.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/62436",risUrl:"/chapter/ris/62436",signatures:"Akikazu Takada, Fumiko Shimizu and Junichi Masuda",book:{id:"7328",type:"book",title:"Melatonin",subtitle:"Molecular Biology, Clinical and Pharmaceutical Approaches",fullTitle:"Melatonin - Molecular Biology, Clinical and Pharmaceutical Approaches",slug:"melatonin-molecular-biology-clinical-and-pharmaceutical-approaches",publishedDate:"November 21st 2018",bookSignature:"Cristina Manuela Drăgoi and Alina Crenguţa Nicolae",coverURL:"https://cdn.intechopen.com/books/images_new/7328.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78984-505-1",printIsbn:"978-1-78984-504-4",pdfIsbn:"978-1-83881-812-8",isAvailableForWebshopOrdering:!0,editors:[{id:"192919",title:"Associate Prof.",name:"Cristina Manuela",middleName:null,surname:"Drăgoi",slug:"cristina-manuela-dragoi",fullName:"Cristina Manuela Drăgoi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",fullName:"Akikazu Takada",slug:"akikazu-takada",email:"takada-1a@kmd.biglobe.ne.jp",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",institution:{name:"Hamamatsu University School of Medicine",institutionURL:null,country:{name:"Japan"}}},{id:"248460",title:"Dr.",name:"Jyunichi",middleName:null,surname:"Masuda",fullName:"Jyunichi Masuda",slug:"jyunichi-masuda",email:"unichi@shimadzu.co.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1. Measurements of TRP metabolites using LC-MS",level:"2"},{id:"sec_1_3",title:"1.1.1. Background",level:"3"},{id:"sec_2_3",title:"Table 1.",level:"3"},{id:"sec_3_3",title:"1.1.3. Analysis of human plasma",level:"3"},{id:"sec_5_2",title:"1.2. Stress and TRP metabolism",level:"2"},{id:"sec_5_3",title:"1.2.1. Stress and TRP metabolites in the brain",level:"3"},{id:"sec_7_2",title:"1.3. TRP metabolites in plasma of patients of depression",level:"2"},{id:"sec_9",title:"2. Discussion",level:"1"},{id:"sec_10",title:"3. Statistics",level:"1"},{id:"sec_11",title:"4. Ethics",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Canli T, Lesch KP. Long story short: The serotonin transporter in emotion regulation and social cognition. Nature Neuroscience. 2007;10:1103-1109. DOI: 10.1038/nn1964pmid:17726476'},{id:"B2",body:'Yates CA, Herbert J. 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Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proceedings of the National Academy of Sciences. 1996;93:12533-12558'},{id:"B31",body:'Schwarcz R, Du F. Quinolinic acid and kynurenic acid in mammalian brain. Advances in Experimental Medicine and Biology. 1991;294:185-199'},{id:"B32",body:'Connick JH, Heywood JC, Sills GJ, Thompson GG, Brodie MJ, Stone TW. Nicotinylalanine increases central kynurenic acid content and anticonvulsant activity. General Pharmacology. 1992;23:235-239'},{id:"B33",body:'Mann JJ, Arango V, Marzuk PM, Theccanat S, Reis DJ. Evidence for the 5-HT hypothesis of suicide. A review of postmortem studies. The British Journal of Psychiatry. 1989;155(Suppl 8):7-14'},{id:"B34",body:'Oquendo MA, Sullivan GM, Sudol K, Baca-Garcia E, Stanley BH, et al. Toward a biosignature for suicide. The American Journal of Psychiatry. 2014;171:1259-1277'},{id:"B35",body:'Lapin IP. Kynurenines as probable participants of depression. PharmakopsychiatrNeuropsychopharmakol. 1973;6:273-279'},{id:"B36",body:'Lapin IP. Antagonism of kynurenic acid to anxiogens in mice. Life Sciences. 1998;63:231-236'},{id:"B37",body:'Pålsson E, Sellgren C, Rydén E, Kizza R, Pelanis A, Zetterberg H, Blennow K, Landén M. Cerebrospinal fluid monoamine metabolite profiles in bipolar disorder, ADHD, and controls. Journal of Neural Transmission (Vienna). Sep 2017;124(9):1135-1143. Epub 2017 Jun 27. PMID: 28656371. DOI: 10.1007/s00702-017-1746-3'},{id:"B38",body:'Berrettini WH, Nurnberger JI Jr, Scheinin M, Seppala T, Linnoila M, Narrow W, Simmons-Alling S, Gershon ES. Cerebrospinal fluid and plasma monoamines and their metabolites in euthymic bipolar patients. Biological Psychiatry. 1985;20:257-269'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Akikazu Takada",address:"takadaa@mwd.biglobe.ne.jp",affiliation:'
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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. 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In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. 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He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}}]}},subseries:{item:{id:"25",type:"subseries",title:"Evolutionary Computation",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403"},editorialBoard:[{id:"111683",title:"Prof.",name:"Elmer P.",middleName:"P.",surname:"Dadios",slug:"elmer-p.-dadios",fullName:"Elmer P. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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