Assignment of the characteristic IR bands of the metal complexes of PZA [1, 14].
\r\n\t
",isbn:"978-1-80356-273-5",printIsbn:"978-1-80356-272-8",pdfIsbn:"978-1-80356-274-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"e1d9662c334dd78ab35bfb57c3bf106e",bookSignature:"Dr. Fabio Arturo Iannotti",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11675.jpg",keywords:"Skeletal Muscle Diseases, Rare Skeletal Muscle Diseases, Basic Research, Molecular Mechanisms of Disease, Translational Research, Diagnostic Technologies, Functional Tests, Disease Models, Innovative Therapies, Drug Repositioning, Drug Discovery, Emerging Technologies",numberOfDownloads:29,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 11th 2022",dateEndSecondStepPublish:"April 19th 2022",dateEndThirdStepPublish:"June 18th 2022",dateEndFourthStepPublish:"September 6th 2022",dateEndFifthStepPublish:"November 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"4 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Fabio Arturo Iannotti received his Bachelor's Degree in Biotechnology Science at the University of Naples “Federico II” in 2006 with the highest degree. In 2010, he graduated with a Ph.D. in Neuroscience at the University of Naples “Federico II”. He published many papers on his areas of research in international peer-reviewed journals and for his pioneering studies has received awards from both national and international scientific societies.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"281317",title:"Dr.",name:"Fabio",middleName:"Arturo",surname:"Iannotti",slug:"fabio-iannotti",fullName:"Fabio Iannotti",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRdOdQAK/Profile_Picture_1644820016099",biography:"Currently researcher at the CNR-ICB Institute of Biomolecular Chemistry of Pozzuoli, Napoli (Italy), Fabio Arturo Iannotti has as major focus of his research activity the role of the endocannabinoid system and TRP in epilepsy and muscle development. Dr. Fabio Arturo Iannotti received his Bachelor Degree in Biotecnology Science (Medical curricula) at University of Naples \\'Federico II\\' in 2006 (with 110/110 cum laude). In 2010, Dr. Iannotti graduated with a PhD in Neuroscience at University of Naples \\'Federico II\\'. The focus of his thesis was on the role of voltage-gated potassium channels Kv7 during the neuronal excitoxicity as well as skeletal muscle cell differentiation. During the three years of the PhD program, Dr. Iannotti has been introduced to the field of ion channels, particularly voltage-gated ion channels; he has been instrumental in setting up RT-PCR and quantitative RT-PCR techniques in our lab, focusing onto research themes which would allow to combine both molecular and functional approaches in the study of ion channels during muscle cell differentiation. He has become familiar with most molecular biology (cloning, mutagenesis, PCR and RT-PCR, Southern and Northern blotting, gene silencing via RNAi, …) as well as with protein biochemistry techniques (protein extraction, immunoprecipitation, Western blotting, in-vitro translation, …) and morphological methods (confocal and conventional immunofluorescence). He is also familiar with imaging tools for intracellular ion concentration analysis, and has more recently gained considerable experience with electrophysiological techniques (specifically, patch-clamp). During this time (2009-2010), he also researched at the University of California-Davis assessing changes to the phosphorylation state of potassium channels in in vivo models of epilepsy. In 2011, he started his postdoc at the Institute of Biomolecular Chemistry (ICB)/ National Council of Research (CNR) and during this period he also visited the University of Reading (2012-2013), researching the potential involvement of TRP channels in epilepsy and muscle development. Since 2014, he was promoted to the position of research fellow at ICB. To date, Dr. Iannotti has published many papers on these areas of research in international peer reviewed journals, and has received awards from both national and international scientific societies for his work. 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Concerning their structure, complexes were considered those compounds which do not fit within the classical theory of valence, meaning that the combination ratio of the elements exceeded their valences. This coordination theory elaborated by Alfred Werner indicated that the secondary valences of the elements are involved in the formation of the second-order combinations leading to the actual representation of the complexes formed by the first coordination sphere marked between brackets [central atom (ligand)] and the second coordination sphere (ionization sphere) coming outside of the brackets. The central atom can be any chemical element; meanwhile, the ligands can be ions, atoms, or neutral molecules, which can act as donors [1]. Neutral molecules or mono-/polyatomic anions which have one or more unshared electron pairs can act as mono-/polydentate ligands, the latter ones form complexes with cyclic structure known as chelates. A large number of pharmaceutical substances behave in vivo or in vitro conditions as ligands and chelating agents [2].
The number and the large structural variety of these complexes could not allow a rigorous systematization, even though some attempts by using certain classification criteria have been made such as the number of the central atoms, the charge of the complex ion, the type of ligands, and the coordination number. The coordination compounds were classified into Werner complexes, complexes with metal-metal bonds, metal carbonyls, clusters, complexes with macrocyclic ligands, molecular complexes (adducts, clathrates), chelates, and metal-organic complexes [1].
Natural metal complexes consisting of a central metal atom or ion (especially of the 3D transition metals) are involved in a plenty of biological mechanisms among which photosynthesis, transport of oxygen in blood, coordination of some metabolic processes, pathological states, enzymatic reactions, etc., even though the metallic ions represent only 3% of the body composition. Many biomolecules (amino acids, peptides, carboxylic acids, etc.) can form metal complexes with different stabilities having biomedical importance. Some drugs have a certain therapeutic effect (e.g., antimicrobial, diuretic, antidepressant) due to the complexation of the metallic ion (Cu2+, Zn2+, Fe2+, Mg2+, etc.) essential for a certain biochemical process. Metal complexes and products containing oligoelements are widely used in therapy due to their pharmacodynamic properties, bioavailability enhancement, and toxicity decrease of some metal ions [1].
The main aspects concerning the formation of complexes between pharmaceutical substances and various ligands are supported by several observations. According to the biological, physiological, and pathophysiological role of metal ions and ligands with pharmacological effect, metal ions present a great importance in carrying out the vital functions of living organisms acting as complexes or chelates and also in the analysis and control methods of drug substances by forming complexes that can be detected by spectral techniques. The use of ligands, chelating agents, or complexes in medicine and biology concerns several purposes such as antidotes in poisoning with metal ions or hydrocyanic acid or cyanides; introduction in the living organisms of some essential metal ions found to be deficient; depriving bacteria, viruses, or microbial enzyme systems of micronutrients essential for their work; or providing toxic metals for the pathogenic agents [2].
Many coordination complexes have been used in medicine containing metals such as platinum (cisplatin as anticancer chemotherapy drug), gold (as auranofin used for rheumatoid arthritis), technetium and rhenium (as radiopharmaceuticals used in imaging and radiotherapy), ruthenium (as anticancer drug), gadolinium, cobalt, lithium, bismuth, iron, calcium, lanthanum, gallium, tin, arsenic, rhodium, copper, zinc, aluminum, lutetium, vanadium, manganese, etc. [3, 4]. Only a reduced number of Co(III) complexes can be mentioned as having biochemical properties: vitamin B12, a natural organometallic complex of Co(III) with glyoxime. Other important examples are the series of Co(III) complexes containing N- and O-donor ligands based on a chelating Schiff base (imidazole, methylimidazole) with efficiency in the treatment of epithelial herpetic keratitis (the molecular target is supposed to be a virus protease containing histidine), adenovirus keratoconjunctivitis, and human immunodeficiency virus type 1. [Co(NH3)6]Cl3 presents potent antiviral activity (against Sindbis virus). Some studies reported also the antibacterial activity of Co(II) and Co(III) complexes against
It was demonstrated that the antibacterial activity was increased upon chelation making the ligand a more powerful agent [5, 6]. The complexation of derivatives of sterically hindered
Metal complexes have become an emerging tool in drug discovery being widely used as therapeutic compounds to treat several human diseases such as carcinomas, lymphomas, infection control, diabetes, anti-inflammatory, and neurological disorders [8, 9]. Due to various implications and applications of complexes (especially the chelates) in the biomedical field, many aspects are required to be studied such as their nature, their stability, the factors determining their formation and stability, and possibilities for preventing some reactions and for releasing a metal ion from a complex; all these are necessary in order to understand how they act in biological processes [2].
The coordination complexes of a wide range of pharmaceutical substances [pyrazinamide (PZA), nicotinamide (NAM), nicotinic acid (NIC), tolbutamide (TBA), theophylline (TEO), captopril (CFL), clonidine (CLN), and guanfacine (GUAF)] with transition metals [Cu(II), Cd(II), Ni(II), Mn(II), Zn(II), and Co(II)] were synthesized and then characterized by using various techniques such as elemental analysis, spectral, electrochemical, thermal, and microscopic methods.
Pyrazinamide (PZA) (pyrazine carboxamide) is a nicotinamide analogue used as a first-line drug to treat tuberculosis. The complexes of PZA with Cu(II) were assessed by different techniques such as elemental analysis, spectral methods [Fourier transform infrared spectroscopy (FTIR), FT-Raman spectrometry, mass spectrometry], and scanning electron microscopy (SEM) coupled with X-ray spectroscopy [energy-dispersive spectroscopy (EDS)] [1, 10–13].
The elemental analysis indicated that the combination ratio of metal:ligand (Me:L) is 1:2 for [Cu(PZA)2]Cl2 and [Cu(PZA)2](C6H5COO)2 complexes. The mass spectra of the complex of PZA with Co(II) benzoate revealed the identity and the purity of PZA and of the complex fragments confirming its structure (Figure 1) [1, 10].
The mass spectra of PZA (A) and [Cu(PZA)2](C6H5COO)2 (B) [
The FTIR spectra of the complexes highlighted that –C═O groups and nitrogen from the pyrazine ring are implied in the coordination process (Table 1) [11]. Comparing the Raman spectra of PZA and of [Cu(PZA)2]Cl2, another analytical evidence for the complex formation is obtained. The appearance of new band characteristic for the Me:L bonds can be observed analyzing in detail the spectral region of low values of wave number (Figure 2) [1, 11, 12].
PZA | [Cu(PZA)2](C6H5COO)2 | [Cu(PZA)2]Cl2 | Assignment |
---|---|---|---|
3410s | 3610w | 3430s | |
3140m | 3170m | 3110m | |
3080 | 3065m | 3070m | |
1705s | 1915w | 1700s | |
1600m | 1590m | 1590m | |
1570 | 1585m | 1585m | |
1530 | 1545s | 1510w | |
1375s | 1380s | 1385s | |
1150w | 1180w | 1170m | |
1090m | 1085w | 1080w | ρ NH2 |
870w | 850w | 870m | |
665w | 680m | 670w | ρ NH2 |
Raman spectra of PZA and of [Cu(PZA)2]Cl2 [
The morphology and the crystal structure of the two complexes were revealed by the SEM images and EDS spectra (Figures 3 and 4). The first complex, [Cu(PZA)2](C6H5COO)2, presented irregular conglomeration with different shapes and dimensions (Figure 3A); meanwhile, the second one, Cu(PZA)2]Cl2, presented acicular and elongated particles with an average size of about 1.5 microns (Figure 4A) [1, 14].
SEM image (A) and EDS spectrum (B) of [Cu(PZA)2](C6H5COO)2 [
SEM image (A) and EDS spectrum (B) of [Cu(PZA)2]Cl2 [
Nicotinamide (NAM) (3-pyridine carboxylic acid amide) is the amide of nicotinic acid playing an important role in the biosynthesis of pyridine nucleotides, and it is a reactive moiety of the coenzyme nicotinamide adenine dinucleotide, a soluble electron carrier in biochemical reactions. The NAM complexes with transition metals [Cu(II), Cd(II), Hg(II)] were synthesized and characterized by using elemental analysis, UV-Vis, and FTIR spectroscopy [1, 15, 16]. The spectral data confirmed tetradentate coordination of NAM with Hg(II), Cd(II), and hexadentate coordination with Cu(II). In the FTIR spectra of these complexes, it can be observed that the characteristic bands of NAM are slightly shifted after coordination (Table 2) [16]. The slight shifting of the bands from NAM complexes with Hg may be explained by the stereochemistry of HgCl2, which is less bulky than Cu(C6H5COO)2 and Cd(SCN)2.
NAM | [Hg(NAM)2]Cl2 | [Cu(NAM)2] (C6H5COO)22H2O | [Cd(NAM)2](SCN)2 | Assignment |
---|---|---|---|---|
3531w | (OH) | |||
3364vs | 3363s | 3369s | 3479s | |
3167s | 3171s | 3207vs | 3176m | |
3065sh | 3071sh | 3071sh | 3072w | |
1654s | 1654vs | 1668vs | 1667vs | |
1622ws | 1623ws | 1632ws | 1618m | |
1577ws | 1577vs | 1596s | 1577s | |
1449m | 1449m | 1490s | 1485m | |
1395ws | 1400m | 1377vs | 1400s | |
1297m | 1296m | 1301w | 1331m | |
1178m | 1179m | 1193w | 1204s | |
1141m | 1142s | 1153sh | 1153m | |
1120m | 1119s | 1116m | 1112m | |
1022m | 1024w | 1025m | 1040m | |
– | 919m | 928w | 937w | |
– | 844s | 853m | 840m | |
771m | 786s | 775w | 770s | |
698m | 700ws | 719w | 719w | |
684m | 686ws | 687s | 687ws | |
633s | 641s | 655w | 657ws |
Assignment of the characteristic IR bands of the metal complexes of NAM [16].
Note: v, very; s, strong; m, medium; w, weak; sh, shoulder; sp, splitting;
Source: Reprinted with permission of Revista de Chimie.
Nicotinic acid (NIC) (pyridine-3-carboxylic acid) known as vitamin B3, niacin, has two important pharmacological properties: peripheral vasodilator and hypocholesterolemic drug. Its complexes with Co(II) and Cu(II) were synthesized and characterized by elemental analysis and spectral methods [FTIR spectroscopy, Raman spectroscopy, and surface-enhanced Raman spectroscopy (SERS)] (Figure 5). The significant differences observed from the spectral data of the metal complexes can be attributed to the coordination process with the metal ions: the stretching vibrations ν(C─C) from the pyridine ring (1500–1600 cm−1) and
Raman (A) and SERS (B) spectra of NIC (a) and its complex with Cu(II) (b) and Co(II) (c) [
Assignment (cm−1) | NIC Raman (cm−1) | NIC SERS (cm−1) | Cu(NIC)2 (CH3COO)2 Raman (cm−1) | Cu(NIC)2 (CH3COO)2 SERS (cm−1) | Co(NIC)2 (CH3COO)2 Raman (cm−1) | Co(NIC)2 (CH3COO)2 SERS (cm−1) |
---|---|---|---|---|---|---|
– | – | – | – | – | – | |
– | – | – | – | – | – | |
1690m | – | – | – | – | – | |
1594m | 1594m | 1594m | – | 1584m | – | |
– | – | – | – | – | – | |
– | 1377m | 1371m | 1377wv | 1389s | 1377wv | |
1298m | – | – | – | – | – | |
1180m | – | – | – | 1198m | – | |
1037vs | 1029s | 1033vs | 1060wv | 1029vs | 1061wv | |
– | – | – | 931m | – | 931m | |
811m | 838wv | 846m | 760wv | 829m | 755wv | |
638m | 653wv | 642m | – | 638m | 648wv | |
– | – | 555wv | 509wv | – | 504wv |
Assignment of the characteristic Raman and SERS bands of the metal complexes of NIC [17].
Note: v, very; s, strong; m, medium; w, weak;
Source: Reprinted with permission of Revista de Chimie.
Guanfacine (GUAF) (
Raman spectra of GUAF and of its metal complexes [
Theophylline (TEO) (3,7-dihydro-1,3-dimethyl,1H-purine-2,6-dione) also known as 1,3-dimethyl-xanthine belongs to the class of peripheral and cerebral vasodilator drugs. Metal complexes of TEO were synthesized having the general formula: [Men(TEO)x]Am ⋅ yH2O, where Me = Cu(II), Co(II), Cd(II), Zn(II), and Ni(II) and A = CH3COO−, C6H5COO−; n = 1, x = 1 or 2, m = 2, and y = 2 or 4. The combination ratio was determined by using elemental analysis and conductometric titration; meanwhile, the number of water molecules was determined by using thermal analysis [2, 19–22].
The combination ratio Me:TEO is 1:2 for the complexes having the acetate anion. The complex [Cu(TEO)2](CH3COO)2 has a high thermal instability even at 40°C, its thermal decomposition being already started. On the thermal curves, eight stages of decomposition, all scarcely separable, can be observed. The first five were weakly endothermic, and three were strongly exothermic. The X-ray diffractogram revealed that this complex crystallizes in the monoclinic system. The microscopic analysis showed a mixture of particles with different shapes: acicular, flake, irregular, and lamellar (Figure 7) [2, 19–22].
Thermogramms TG, DTG, and DTA (A); X-ray diffractogram; (B) and SEM images (C) of [Cu(TEO)2](CH3COO)2 [
In the case of [Cd(TEO)2](CH3COO)2, the last stage of thermal decomposition was not achieved in the investigated temperature range; therefore, heating was required up to a higher temperature (850°C) when constant weight was reached corresponding to the cadmium oxide. The complex crystallizes in the monoclinic system, and it presents microcrystals with parallelepiped shape (Figure 8) [2, 19, 21, 22].
Thermogramms TG, DTG, and DTA (A); X-ray diffractogram; (B) and SEM images (C) of [Cd(TEO)2](CH3COO)2 [
The thermal decomposition of [Co(TEO)2](CH3COO)2 takes place in four stages: one endothermic and three exothermic. It presents monoclinic crystal system, and the microcrystals have a tabular form (Figure 9). The complex [Zn(TEO)2](CH3COO)2 presented similar properties as [Cd(TEO)2](CH3COO)2 complex [2, 19, 21, 22].
Thermogramms TG, DTG, and DTA (A); X-ray diffractogram; (B) and SEM images (C) of [Co(TEO)2](CH3COO)2 [
The endothermic peak at 272°C, which is characteristic for TEO decomposition, is not found in the differential scanning calorimetry (DSC) curves of the complexes, being a credible argument for the complex synthesis and not as a simple mechanical mixture (Figure 10) [2, 19].
DSC thermogramms of metal complexes of TEO [
The FTIR data also indicated the complex formation: the disappearance of the symmetric vibration band of ─C═O from TEO at 1717 cm−1 in the complexes spectra indicating that this bond is involved in the formation of Me:TEO coordinative bond; the deformation vibration of Me:N bond found at 570–685 cm−1, the appearance of symmetric and asymmetric stretching vibrations of the ─COOH group (1260–1250 and 1535–1530 cm−1), and the possibility of coordinating also the water of crystallization (appearance of large bands at 3050–3500 cm−1) (Figure 11) [2, 19, 21, 22].
FTIR spectra of TEO and of its metal complexes (acetate anion).
The combination ratio Me:TEO is 1:1 for the complexes having the benzoate anion: [Co(TEO)](C6H5COO)2·2H2O, [Ni(TEO)](C6H5COO)2·2H2O, and [Cu(TEO)](C6H5COO)2·2H2O. Their thermal decomposition takes place in four stages, the first one being the stage of loss of water of crystallization (Figure 12A). The FTIR data are similar with those of the complexes mentioned above (having the acetate group as anion); in addition, the specific vibration band of the aromatic ring (1438, 1442, 1440 cm−1) appears. The microscopic image of [Co(TEO)](C6H5COO)2 showed the acicular shape of the particles (Figure 12B) [2, 20].
Thermogramms TG, DTG, and DTA (A) and SEM images (B) of [Co(TEO)](C6H5COO)2 [
The chemical structure of captopril (CPL), a dipeptide derivative of
The molecular formula and weight | Color | Melting point (°C) | C% Found/calculated | H% Found/calculated | N% Found/calculated | S% Found/calculated |
---|---|---|---|---|---|---|
[Cd(CPL)2][HgI4] M = 1255.18 | White | 210 | 17.09/17.21 | 2.56/2.39 | 1.881/2.23 | 5.579/5.099 |
[Zn(CPL)2][HgI4] M = 1244.18 | White | 165 | 16.94/17.8 | 3.019/2.48 | 1.866/2.31 | 5.547/5.29 |
[Ni(CPL)2][HgI4] M = 1199.48 | Greenish yellow | 170 | 18.07/18.01 | 3.022/2.5 | 1.955/2.33 | 6.083/5.33 |
[Co(CPL)2][HgI4] M = 1199.68 | Light pink | 180 | 17.84/18.01 | 2.866/2.51 | 1.938/2.31 | 6.148/5.43 |
[Mn(CPL)2][HgI4] M = 1195.68 | White crystals | 182 | 18.04/18.06 | 2.648/2.50 | 1.946/2.34 | 5.85/5.35 |
CPL forms complexes with transition metals mentioned above in the presence of tetraiodomercurate anion, [HgI4]2−. The formation and the structure of these complexes are observed in the data of the elemental analysis and in the UV and IR spectra of the complexes with changes of the wavelength values and of absorbance due to the presence of Me:CPL bonds. In the IR spectra of the complexes, a diminution of the band at 1748 cm−1 of ─C═O from the carboxyl group, in comparison with the IR spectrum of CPL, was observed. A wider band appeared at 1600 cm−1 due to the overlapping of the bands corresponding to ─C═O from the amide group. In addition, a new band is observed at 1450 cm−1 due to ─C═O from the carboxyl group (─COO−). In the IR spectra of the Zn:CPL complex, the band corresponding to ─C═O from carboxyl group decreased. It is possible that the reaction with some metals was not completely performed or some degradation products of CPL may be involved in the complexation reaction. In the case of the complex Cu2IICPL2(H2O)2, the IR spectra have indicated the participation of ─COOH, ─C═O, and ─SH groups in coordination along with H2O included in the inner coordination sphere [23, 24].
The UV spectra of the complexes were compared to the UV spectrum of CPL in dimethylformamide establishing the parameters presented in Table 5 (A%1 cm = 190 for 2.5 μg% CPL) [23, 24].
Complex | λ (nm) | A%1 cm | Concentration (μg %) |
---|---|---|---|
CPL–Cd | 300 | 270 | 5 |
CPL–Zn | 300 | 400 | 5 |
CPL–Ni | 300 | 475 | 4 |
CPL–Co | 300 | 250 | 8 |
CPL–Mn | 321 | 520 | 4.5 |
The parameters of the metal complexes of CPL from UV spectra [23].
Source: Reprinted with permission of Editura Universităţii din Oradea.
Tolbutamide (TBA) (
Clonidine (CLN) (2[(2,6-dichlorophenyl)imino]-imidazolidine) is a centrally acting α2 adrenergic agonist used as antihypertensive drug. Metal complexes of CLN such as [Me(CLN)2][HgI4] where Me = Cd(II), Mn(II), Ni(II), and Cu(II) were synthesized and studied by elemental analysis, FTIR spectroscopy, Raman spectroscopy (Figure 13), and EPR spectroscopy confirming the structure and the changes in the complex conformation [28].
Raman spectra of CLN and of its metal complexes.
The study of the complexes structure and of their biological importance represented the major research interest toward the use of organic drugs as ligands in coordination chemistry for their application in the biomedical field.
The molecules of the pharmaceutical substances have one or more unshared electron pairs that can function as ligands. In fact, many of the basic components of living organisms (amino acids, peptides, proteins, hormones, lipids, carbohydrates, etc.) may function as ligands because they contain donor atoms in their molecules such as nitrogen, oxygen, sulfur, and phosphorus. It is well known that many molecules of drug substances act as ligands both in vitro and in vivo conditions. It is noteworthy to mention that in vivo these ligands will compete for a particular metal ion with a variety of other ligands determining that the extrapolation of this in vitro behavior should be done with moderation. It should always be taken into consideration that the therapeutic effect will be mainly influenced by the conformation of the drug ligands molecules and by their ability to combine with receptors.
Thus, the use of these metal complexes in the biomedical field can be realized by various purposes such as the introduction in the body of deficient metal ions, the use of the ligands as antidotes in various intoxications with metals, and the acquirement of pharmacotherapy effects by blocking metal ions essential for some enzymatic systems. Metal ions are of great importance not only in the vital functions of living organisms, but also they can be intensively used in analysis and control methods for pharmaceutical substances by forming complexes that can be detected by using different physicochemical methods such as spectroscopy, chromatography, microscopy, etc.
Transition metal complexes find their application in catalysis, material synthesis, photochemistry, therapy, and diagnostics. Various chemical, optical, and magnetic properties of the metal complexes of some pharmaceutical substances (pyrazinamide, nicotinamide, nicotinic acid, tolbutamide, theophylline, captopril, clonidine, and guanfacine) have been studied by using a wide range of techniques. The spectral methods such as Fourier transform infrared spectroscopy, Raman spectroscopy, surface-enhanced Raman spectroscopy, X-ray spectroscopy, mass spectrometry, ultraviolet
Cells adhere to the matrix and other cells around them, which fundamentally impacts their behavior. A thorough understanding of these adhesive interactions is also important to produce artificial tissues. Cell adhesions are formed by cell adhesion molecules on the cell surface such as integrins and cadherins which bind to the matrix and cadherins on neighboring cells, respectively [1]. These adhesion molecules transmit both physical and chemical signals between cells and their environment via the underlying cytoskeleton and intracellular signaling cascades [2].
Cell–cell connections induce and receive biochemical signals and contractile forces from adjacent cells, and it is through theses stresses that cellular and tissue homeostasis is maintained [3]. The most abundant and well-studied cell–cell adhesion molecules are the cadherins. Cadherins such as E-cadherin, N-cadherin, and P-cadherin, consist of five extracellular domains with a calcium-binding site between each domain (Figure 1). The cell–cell adhesion is initiated by the cadherins on adjacent cells forming homophilic interactions via the exchange of β-strands between the first extracellular domains [4] and from here the cadherin signal is transmitted into the cell via an intracellular tail domain. Force-dependent conformation changes in cadherins lead to the recruitment of binding partners such as α-catenin, β-catenin, and vinculin thereby conveying the chemical signal to the intracellular actomyosin network. These ensuing biomechanical and biochemical cascades direct scaffolding proteins toward cellular pathways regulating division, survival, structural morphologies [5, 6] epithelial-mesenchymal transition (EMT), cell-sorting, and collective cell migration [7].
E-cadherin dependent cell–cell adhesion. The E-cadherin consists of five extracellular domains, one transmembrane domain and an intracellular domain. During binding of two E-cadherin molecules the proteins p120, β-catenin, ɑ-catenin, and vinculin get recruited to the intracellular domain leading to cytoskeletal adhesion and actomyosin based activation.
Altering the number of cellular adhesions is critical to many biological processes during tissue development and cancer progression. For instance, the interconnected nature of epithelial cells, which line the surface of organs, tissues, and blood vessels, designates their polarity, which is critical to their function. EMT takes place when epithelial cells lose the adhesions to other cells and therefore their basal-apical polarity. The resulting mesenchymal cell has increased cellular motility and invasiveness. This process takes place naturally to produce the mesoderm, one of the germ layers, during embryonic development [8, 9], pro-inflammatory wound healing [10], and during cancer cell metastasis [11, 12, 13].
Before the development of the germ layers, the embryonic stem cells in the inner mass of the blastocyst are largely epithelial in characteristic; however, during germ layer development, gastrulation, the epithelial-like cells undergo EMT to form the mesoderm. I
EMT extends to carcinomas as well, where a subpopulation of self-renewing cells, known as cancer stem cells, can efficiently generate new tumors. This can be seen in mammary carcinomas following the induction of EMT, which promotes the generation of clusters of invasive mammary gland cells [14]. The extent of these epithelial connections can also be seen in metastatic experiments involving the mammary cancer cell line MCF-7, which maintains an epithelial-like phenotype. In these experiments, MCF-7 is added on top of mammary endothelial cell sheets, and the invasiveness of MCF-7’s was evaluated over increasing crossflow, it was revealed that the majority of MCF-7 cells could not form strong adhesions thereby failing to invade. Instead, the MCF-7 s remained rounded and rolled across the surface of the endothelial sheet [13].
Cadherin connections also guide cell migration through their intracellular connection to the cytoskeleton. For instance, in experiments examining the effect of cadherin adhesions in binary cell systems, it was revealed that single adhesions quickly recruit more cadherins to the initial contact site. Additionally, each recruited cadherin binds to the actin cytoskeleton preventing its depolymerization and enabling actomyosin-based mechanical signals [2, 15, 16, 17]. Additionally, cadherin-based stabilization of actin in migrating cells leads to
Another aspect for which controlled cell–cell adhesions are crucial is in bottom-up tissue engineering, in which single cells are organized into either planar or three-dimensional structures [20]. Since bottom-up engineering does not rely on external matrices to sequester the cells and instruct cellular arrangement the ability to spatiotemporally control the cell–cell connections is critical to building the desired structure. Techniques for creating bottom-up tissues include bioprinting, construction of cell sheets, and self-assembly of multicellular aggregates [20, 21, 22, 23].
Self-assembled multicellular aggregates form by mixing multiple cell types such that microtissues with desired organization form. Generally, these structures form based on minimizing the potential internal energy resulting from cell–cell adhesions [24, 25]. Self-assembled aggregates have been used to construct multicell neuro-organoids comprised of cortical neural progenitor cells, endothelial cells, and mesenchymal stem cells. Different aggregates of each or a mix of two cells were first created in low-attachment 96-well plates. Following aggregate production, aggregates were then mixed to fuse the three cell populations. The resultant aggregate then sorted to form discrete layers within the aggregate. The cortical neural progenitor and endothelial cells developed into vascularized cortical brain tissue, while the mesenchymal stem cells took on a supportive role in the core of the aggregate [26]. With the ability to spatiotemporally control cell–cell adhesions it becomes possible to self-assemble cells together to produce more complex tissues that better recapitulate the
The cell sorting observed in tissues, self-assembled aggregates, and the developing embryoblast can be described by the differential adhesion hypothesis (DAH). The DAH explains cell sorting by comparing it to that of liquid mixtures, whereby the components (liquids or cells) arrange so that the internal free energy from cellular adhesions is reduced to a minimum to attain thermodynamic equilibrium [27, 28, 29, 30]. Equilibrium is achieved via the active or passive motility of cells in the tissue rearranging with respect to each other to minimize stress and strain thereby limiting the internal energy [31]. Other aspects such as the cell’s ability to round up to minimize their surface area, spreading of one cell over another, the fusion of two cellular aggregates, the sorting out behavior of mixed cell populations, and the hierarchy of the layering of two cell types further prove the analogy to liquid mixtures [31, 32, 33]. The DAH describes three different cases for multicellular assemblies in a mixture of two cell types (Figure 2) [30].
Differential adhesion hypothesis (DAH). Different cell assemblies form at equilibrium depending on the work of adhesion between cells of type a (Wa), cells of type b (Wb) and cells of type a and type b (Wab).
In this condition cells of type A and type B stay intermixed when the work of adhesion between the two cell populations (Wab) is higher than the work of cohesion of a single cell type (Wa and Wb) as this results in the maximal adhesion.
An enveloped arrangement of cells, occurs when one cell type is in the center and the secondary at its periphery. This arrangement forms when the average work of cohesion of cell type A and cell type B is greater than the work of adhesion between the two cell types and the work of cohesion of one cell type is smaller than the work of adhesion between the cell types. Herein, the cell type with the stronger cohesion, type A, forms the core and the less cohesive cell type, type B, surrounds this core.
In a self-isolated system the two cell types form separate assemblies because the work of adhesion between the cell types is smaller than the work of cohesion within either population. In this case each cell type will self-isolate with no intermixing.
Numerous studies with cells expressing different types and amounts of cadherins have demonstrated these sorting schemes [34, 35, 36]. These studies show that the differences in homophylic and heterophilic cell–cell adhesions determine the outcome and the origin of these differences on adhesions are not important for the result.
Currently, there are only a few tools for controlling cell–cell adhesion, which enable the studying of the underlying biology and for bottom-up tissue engineering. Important aspects to consider in the control of cell–cell adhesions are their specificity, their dynamics, and most importantly, their spatiotemporal regulation. The current approaches can be divided into two; the modification of the cell surface with chemically reactive groups and the genetic modification of cells to alter the expression of cell adhesion molecules [37].
In the following sections, we will discuss options of regulating cell–cell adhesions using reactive chemical groups and then consider photoregulation of cell–cell adhesions using light-responsive small molecules and finally optogenetic approaches. Light is especially advantageous as a trigger for cell–cell adhesions since light, as opposed to other stimuli like chemical inputs, temperature, redox etc., can be delivered with superior spatial and temporal control. Using a focused beam of light enables precise subcellular delivery, which can exclude the surrounding area. Secondly, light allows for temporal control as it can be turned on or off instantly making delivery or removal at the desired point instantaneous [38, 39].
A general strategy for initiating user-controlled cell–cell interactions is to introduce reactive chemical groups on the cell surface. These chemical groups are not genetically coded and thus do not require genetic engineering to add them to the surface. Such chemical groups are introduced through the fusion of lipid vesicles containing the chemical reactive groups or through metabolic labeling with non-natural sugars bearing bioorthogonal functional groups with the cell [40]. For instance, complementarily reactive ketone and oxyamine groups or alkyne and azide groups can be introduced on the plasma membrane of cells [41]. Consequently, when cells with complementary reactive groups are mixed, the functional groups on the cell surfaces react and cells are connected through covalent bonds [42, 43]. In general, so-called click reactions, that take place in water, do not form toxic side products and do not interfere with other functional groups found in biomolecules. Alternatively, noncovalent interactions with high specificity can be used to form cell–cell adhesions. For this purpose, the binding of biotin to streptavidin [44, 45, 46] or the hybridization of complementary single-stranded DNA [47, 48, 49] is employed. DNA-based cell–cell adhesions open the possibility to form diverse structures with varying cell types and cellular connectivity owing to the high specificity of these interactions; however, DNA adhesions show limited reversibility making migratory sorting impossible, and covalent and strong noncovalent links between cells permanently glue them together [50].
Light sensitive small molecules, such as nitrobenzenes and azobenzenes, have been used to control cell–cell adhesions in space and time. For example, light cleavable nitrobenzene groups can be introduced to oxyamine linkers at the cell surface. When this cell population is mixed with a second population of cells with a ketone group at the cell surface multicellular clusters formed. These cell cluster can then be broken up into single cells upon UV-light illumination since UV-light cleaves the nitrobenzyl moiety [51]. Such a photocleavable linker only allows for a single reversion of the cell–cell adhesions. To achieve cell–cell adhesions that can be switched on and off repeatedly a linker with a photoswitchable azobenzene group was developed. β-cyclodextrins can be clicked onto the surfaces of cells and when a divalent photoswitchable azobenzene (azo) linker (azo-PEG-azo) is added in the dark the cells will link together. This is because, in the dark, the trans configuration of the azobenzenes binds to the cyclodextrin moieties linking the cells together. Upon UV illumination the azobenzene switch to the cis conformation, which results in the release from the cyclodextrin and the dissociation of the cell–cell interactions. The azobenzene can then be switched back to the trans configuration with blue light illumination, thus allowing for the formation of new cell–cell adhesions [52]. These studies represent great advances in the field and allow for spatiotemporal control over cell–cell adhesions. However, the use of UV-light is damaging to DNA and therefore to cells, and secondly, the chemical modifications cannot be maintained over long periods of time. Thus, a system which utilizes biocompatible light and can be expressed over long times would be more beneficial to bottom-up tissue engineering since cell proliferation is a key component of any built tissue. For this purpose, a genetically engineered system, which allows for propagating the modification at the cell surface would be desirable.
Cell–cell adhesions can be photoregulated by expressing bioartificial light-responsive proteins on the surfaces of cells as adhesion receptors. Numerous light-responsive proteins from algae, plants, bacteria, and engineered proteins change their conformation upon light illumination and bind to other proteins in a light-dependent manner through non-covalent protein–protein interactions [53, 54, 55, 56]. In these optogenetic approaches, complementary light-dependent binding partners are expressed in the surfaces of different cell types by transfecting these proteins along with a plasma membrane localization sequence and a membrane anchoring sequence. Following translation, the localization sequence ensures that the protein is exported to the cell membrane where the extracellular portion operates as a bioartificial cell adhesion receptor [51, 52, 57]. For instance, the proteins Cryptochrome 2 (CRY2) from
Optogenetic proteins bind either in hetero or homophilic complexes. In heterophilic optogenetic systems an optogenetic protein undergoes conformational changes that enable the binding to a target protein. Homophilic optogenetic proteins also undergo conformation changes, but here a homomer is formed. iLID (improved light induced dimer), CRY2 (Cryptochrome 2), CIB1/N (cryptochrome-interacting basic helix–loop–helix/truncated), Cph1 (cyanobacterial phytochrome 1).
The large repertoire of photoswitchable protein–protein interactions allows for the formation of bioartificial cell–cell adhesions with different properties in terms of cell–cell adhesion mode, the light of color the adhesions responds to, reversion kinetics in the dark, and cell–cell adhesion dynamics [53, 54, 55].
In biology, cells can either interact with cells of their own type forming homophilic interactions or cells of another type forming heterophilic interactions.
To obtain light-responsive homophilic cell–cell adhesion, proteins that homodimerize under light are used as a mediator of cell–cell adhesion. For this purpose, the proteins Vivid, a member of the light oxygen voltage (LOV) domain from
Co-culture of optogenetic proteins results in cluster segregation. When colloidial particles are labled with the iLID/Nano, nMag/pMag, or nMagHigh/pMagHigh clusters of particles can be seen to form with respect to the kinetics of the system (adapted from Müller et al. [
Light responsive heterophilic cell–cell adhesions, can be achieved by proteins that heterodimerize under light to form cell–cell adhesions. For this purpose, different heterodimerization pairs that form under blue light and reverse in the dark were used. These include the binding of the improved light-induced dimer (iLID) to Nano [61], the binding of the Vivid-based proteins nMag and pMag and the previously-described binding of CRY2 to CIBN. These different protein pairs provide different interaction strengths, reversion kinetics in the dark, and protein–protein dynamics.
The assembly of multicellular structures does not just depend on the strength of the underlying cell–cell adhesions but also their dynamics. If cell–cell adhesions are dynamic, meaning that formed protein–protein interactions constantly form and disassemble within the chemical equilibrium, cells can move with respect to each other and maximize the number of adhesive contacts they form. This scenario is observed in mixtures of iLID and Nano expressing cells, which assembled into spherical and compact clusters. If cell–cell adhesions are not dynamic, meaning that once protein–protein interactions form that they do not reverse, cells stick to the first cell they meet and cannot move to areas with potential higher numbers of adhesions. For example, mixtures of nMagHigh and pMagHigh or nMag and pMag expressing cells assemble into ramified branched structures, which are kinetically trapped. Optogenetics allows for the altering of the dynamics of the cell–cell adhesion by turning light on and off. The ramified structures formed with nMag and pMag cells could then be converted into compact spheres under pulsed illumination (5 min on, 5 min off), allowing the adhesions to dissipate and the cells to move.
Different types of photoswitchable cell–cell adhesions can be mixed to obtain cell sorting within multicellular mixtures and organize cells as predicted by the DAH. For example, when cells expressing Vivid or Cph1 at their cell surface were mixed and illuminated with either blue or red-light clusters of cells with Vivid or Cph1 cells formed, respectively. When both blue and red light was used self-isolated clusters containing either Vivid or Cph1 cells were observed (Figure 4) [57]. That means that the adhesive force for Vivid and Cph1 is lower than that for the homodimers formed for each system due to the specific protein–protein interactions. Similarly, also different pairs of heterophilic cell–cell adhesions can be used to achieve self-sorting in mixtures containing four different cell types. In mixtures of iLID, Nano, nMag, and pMag expressing cells, two types of multicellular aggregates assembled each containing one of the protein pairs (iLID/Nano or nMag/pMag) [62]. It should be noted that cell sorting is only possible if the system is under thermodynamic control and is not observed if kinetically trapped structures form. Therefore, mixtures of iLID, Nano, nMagHigh and pMagHigh do not sort into distinct clusters.
Cell–cell adhesions play an important role in many cellular functions, and the adhesions resulting from the optogenetic proteins are no different. Using CarH based homophilic cell–cell adhesions, the spatiotemporal control of migrations was assessed by measuring the rate and the morphology of cells migrating during a wound-healing assay. The spatiotemporal element was carried out by illuminating discrete sections to depolymerize the cell–cell adhesion. Cells with intact CarH adhesions in the dark showed significantly enhanced migratory potential compared to cells illuminated with green light, which dissociate the cell–cell adhesions. This was characterized by cells remaining together and thus migrating as a single cell wall resulting in faster migration. Cells that were illuminated with blue-green light broke away from the migratory front and engaged in random walking resulting in a slower overall migration rate [59].
Additionally, spatiotemporal control of the cell–cell adhesion complex has been shown in experiments where the β-catenin binding domains on E-cadherin and α-catenin have been replaced with the Halo and SNAP tags, respectively. The Halo/SNAP system incorporates the UV-light photocleavable small molecule Ha-pl-BG, so adhesions can be reversed upon UV illumination. This system was then applied to MDA-MB-468, which do not express endogenous E-cadherin to assess the efficacy of the system. Using the system cell–cell adhesions could only be observed when the cofactor was present and were degraded rapidly under UV-light. To illustrate the spatiotemporal control, A431 cells, with knocked out α-catenin, were labeled with the Halo/SNAP system and cultured overnight to initiate connections between cells. Specific adhesions between cells were then targeted and illuminated with UV-light. Only the targeted connections were degraded leaving the other connections intact.
The spatiotemporal nature of cadherin-based cell–cell adhesions enables cells to self-sort, assemble into tissues, or can lead to cellular differentiation. However, these adhesions cannot be exogenously controlled, and as such make the construction of bottom-up tissues difficult to manage. Chemical means for binding cell membranes together are too rigid and offer limited reversibility. There is also a lack of spatiotemporal control. However, light is non-invasive, highly biocompatible, and can be delivered in a spatiotemporal fashion. Through the delivery of optogenetic proteins to the cell membrane, the construction of spatiotemporal cell–cell adhesions has been achieved. These proteins can respond to a wide range of wavelengths enabling the use of multiple pairs to construct larger structures, form reversible adhesions, and offer superior kinetics to other adhesion methods.
This work was funded by the European Research Council ERC Starting Grant ARTIST (# 757593).
The authors have no conflicts to disclose.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Overall, optical methods can support traditional periodontal diagnosis and improve treatment planning and clinical periodontal care.",book:{id:"7244",slug:"periodontology-and-dental-implantology",title:"Periodontology and Dental Implantology",fullTitle:"Periodontology and Dental Implantology"},signatures:"Fardad Shakibaie and Laurence Walsh",authors:[{id:"179467",title:"Prof.",name:"Laurence",middleName:null,surname:"Walsh",slug:"laurence-walsh",fullName:"Laurence Walsh"},{id:"235443",title:"Dr.",name:"Fardad",middleName:null,surname:"Shakibaie",slug:"fardad-shakibaie",fullName:"Fardad Shakibaie"}]},{id:"24363",title:"Biomechanics of Tooth-Movement: Current Look at Orthodontic Fundamental",slug:"biomechanics-of-tooth-movement-current-look-at-orthodontic-fundamental",totalDownloads:26816,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"277",slug:"principles-in-contemporary-orthodontics",title:"Principles in Contemporary Orthodontics",fullTitle:"Principles in Contemporary Orthodontics"},signatures:"Joanna Antoszewska and Nazan Küçükkeles",authors:[{id:"50158",title:"Prof.",name:"Joanna",middleName:null,surname:"Antoszewska",slug:"joanna-antoszewska",fullName:"Joanna Antoszewska"}]},{id:"71271",title:"Flap Techniques in Dentoalveolar Surgery",slug:"flap-techniques-in-dentoalveolar-surgery",totalDownloads:2628,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Most dentoalveolar procedures involve the reflection of mucosal flaps. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. 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. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. 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. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"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 scientist and Principal Investigator 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 the 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 artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is 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}]}},subseries:{item:{id:"38",type:"subseries",title:"Pollution",keywords:"Human Activity, Pollutants, Reduced Risks, Population Growth, Waste Disposal, Remediation, Clean Environment",scope:"\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11966,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,series:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713"},editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",slug:"meng-chuan-ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",slug:"olga-anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},onlineFirstChapters:{paginationCount:6,paginationItems:[{id:"83073",title:"Dental and Orofacial Trauma Impacts on Oral-Health-Related—Quality of Life in Children: Low- and Middle-Income Countries",doi:"10.5772/intechopen.105845",signatures:"Yolanda Malele-Kolisa, Nazia Khan, Mpho P. 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