Nitric oxide synthase enzymes functions on health/pathological conditions.
\r\n\tThis book will intend to look at different migrant patterns, voluntary and involuntary migration, over the last three centuries. What influenced people to leave their home countries, family, and friends and settle somewhere else? The book may include histories of the 19th century, consider tragedies and movements activated by political events in the 20th century, and/or look at recent events of the 21st century. Push and pull factors are important points. While most of us may be influenced in a negative way by the current happenings in Eastern Europe, the Russian invasion and resulting tragedies also demonstrate some very positive human traits – the preparedness of Ukraine’s surrounding countries to help those in need and to provide a safe place for the present.
\r\n\tWhether one looks at voluntary or involuntary migration into any country, after a period of adjustment, migrants do play a positive role. The research found that migrants contribute to the economy (food, shelter, employment, tax) and enrich a country’s cultural norms. Prerequisites for successful settlements are that the host society adopts a tolerant approach and that the migrants recognize the law and the language of the host country. Nothing is ever easy or without controversy, but I am a migrant (German Australian), and life in Australia has been relatively harmonious. Issues that could be considered in the book are multicultural societies (do monocultural societies still exist?) and theories of acculturation versus integration (settlement processes).
\r\n\tTwo further issues are very important in relation to human migration. There is climate change, global warming, and the environment, which clearly affect people’s movement. Small island populations are very concerned about rising sea levels. 2021 has also seen floods costing human lives: Turkey (August 2021), Brazil (December 2021), Chile (January 2021), and South India (November 2021), to name but a few. In Australia (March 2022), farms and whole townships in New South Wales and Queensland have been flooded for the second time in five years, and plans to resettle these towns are considered. Official and social media provide ample coverage of the events, which leads me to the next issue. There is today’s very important role of the media, of the official and social media. We are constantly bombarded with images of human war tragedies and flood victims. People in industrialized, western countries must be the best-informed populace. How far do the images and up-to-date TV news influence us, make us change our behavior, and perhaps even consider us more generous than we have been?
\r\n\tClimate change and the media are relatively new to the human migration debate, but both issues play important parts, and some interesting discussions are appreciated.
\r\n\t
Three isoforms of nitric oxide synthase (NOS) have been identified: two constitutive enzymes, neuronal NOS (nNOS) and endothelial NOS (eNOS), and one inducible enzyme (iNOS). These three isoforms of the enzyme nitric oxide synthase (NOS) that are present in the central nervous system (CNS) can produce nitric oxide (NO). eNOS is expressed in the vascular endothelium and choroid plexus; neuronal NOS is mainly expressed in neuronal cell bodies, especially in the cortex, hippocampus, hypothalamus, olfactory bulb, claustrum, amygdala, and thalamus; and inducible NOS is expressed in macrophages, glial cells, infiltrating neutrophils, and, to some extent, neurons [1]. It has also been reported that eNOS can be found in a subset of neurons and astrocytes and that nNOS can be found at low levels in astrocytes [2]. Because these enzymes may have different sites of expression and activation, they have a pivotal role in the divergent functions of NO [3].
Several studies have demonstrated that NO, a freely diffusible gaseous compound, has an important role in a variety of neurobiological processes [4]. Numerous functions of this regulatory molecule have been identified in the CNS, in the process of endothelium‐dependent vasodilatation [5–8], in neurotransmission [9, 10], and in host‐defense mechanisms [11, 12].
NO is produced from the oxidation of the terminal guanidine nitrogen of the amino acid arginine. This reaction is catalyzed by the NADPH‐dependent enzyme, nitric oxide synthase (NOS). After its formation, NO diffuses outside the cell [13]. NO derived from eNOS maintains the CNS microcirculation [14] by inhibiting platelet aggregation and leukocyte adhesion and migration [15]. NO derived from nNOS is an important neurotransmitter related to neuronal plasticity, memory formation, regulation of CNS blood flow, and neurotransmitter release [16, 17].
Under physiological conditions, the concentration of NO fluctuates within the range of low values [18] and is produced mainly by nNOS and eNOS. Unlike the other two enzymes, iNOS is not expressed unless it is induced by inflammatory mediators, cytokines, and other agents, such as endotoxins [19]. Due to its calcium‐independent activation, iNOS can produce a large amount (100–1000 times greater) of NO in relation to eNOS and nNOS [20]. Until the enzyme is degraded, iNOS constitutively produces NO [21].
NO binds to guanylyl‐cyclase, which is a soluble NO receptor and, through cGMP‐mediated signaling, acts either as a post‐ or a presynaptic messenger [22]. As a neurotransmitter, NO may activate the cGMP‐dependent protein kinase G (PKG) pathway that phosphorylates synaptophysin, which is critical for fusion of presynaptic vesicles, thereby potentiating and facilitating neurotransmission [22] (Figure 1). NO also acts on inhibitory gamma‐aminobutyric acid (GABA)‐ergic synaptic transmission via cGMP‐dependent pathways as well as on ion channels and exchangers [9].
NO act as an unconventional neurotransmitter that is not stored in synaptic vesicles and not released upon membrane depolarization; it releases as soon it is synthesized and does not bind to any receptors, but diffuses from one neuron to another. NO stimulate soluble guanylyl‐cyclase to form the second messenger molecule, cyclic guanosine monophosphate (cGMP) either as a post‐ or a presynaptic messenger. PKG, protein kinase G; ERK, extracellular signal‐regulated kinases; LTP, long‐term potentiation. Images:
The brain relies on a constant and adequate supply of oxygen and glucose that is provided by blood. Cerebral blood flow is altered in response to both neural activity and humoral
All NOS isoforms have phosphorylation sites for different protein kinases, including protein kinase A, B, and C, and calcium‐calmodulin kinase [24]. NOS enzymes are very important for the maintenance of physiological mechanisms within an organism, and the genetic ablation of NOS in mice has been informative for establishing the functional roles of NOS‐generated NO in different systems [25]. For instance, nNOS‐KO mice present with intense gastroparesis due to impaired vagal innervation of stomach muscle cells [26], decreased apoptosis induced by striatal N‐methyl‐D‐aspartate (NMDA) microinjections [27], and early dysfunction of hippocampal‐dependent spatial memory [28]. Additionally, disrupting the gene that encodes eNOS in mice‐induced spontaneous systemic and pulmonary hypertension [29] and inhibited growth factor‐mediated angiogenesis [30]. Thus, NO acts through numerous mechanisms of different physiological systems and in living cells.
Shortly after its identification, NO emerged as a possible mediator of neurovascular coupling. Neurovascular coupling is an active mechanism with vessel diameter alterations in response to increased metabolic demands from neuronal activity. Under these conditions, NO acts as a potent vasodilator that is released during enhanced neuronal activity and is well suited to mediate the coupling between neuronal activity and cerebral blood flow [31].
The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate is an initiator of the reaction that forms NO. NO can act as a “double‐edged sword”. Whereas NO supports vascular homeostasis in the endothelium‐dependent vasodilatation, its over‐ or underproduction is linked to pathological conditions [4].
NO is also an important mediator under pathological conditions. For instance, in brain ischemia‐reperfusion injury, NO formation is initially increased and has a protective function by inducing collateral perfusion as a result of its powerful stimulatory effect on vasodilatation and angiogenesis [32]. NO donors induce neuroprotective effects.
NO can exist in distinct oxidation/reduction states and present dual biological actions as either a neuroprotective or a neurotoxic molecule [4]. Under physiological conditions, nNOS produces hydrogen peroxide (H2O2) and superoxide (O2•−) in addition to NO [33].
The downstream cascade in the breakdown of the BBB appears to be mediated by eNOS activity; the systemic administration of a selective eNOS inhibitor abrogates VEGF‐A‐induced BBB disruption and protects against neurologic damage in models of inflammatory disease [34, 35]. Nevertheless, it was suggested that eNOS‐derived NO is a neuromodulator that participates in the BBB‐mediated control of the cerebellum in experimental models [36].
Curiously, perivascular macrophage‐derived iNOS‐generated NO, that strategically localizes to leukocytes at brain penetration sites, can serve as a negative feedback regulator that prevents the unlimited influx of inflammatory cells by restoring BBB integrity [37].
In the brain, NOS regulates cerebral blood flow and neurotransmitter release, and the proper operative eNOS/NO system accounts for the microenvironment homeostasis that is essential for the normal functioning of neurons and glial cells [38]. Therefore, the NO produced by NOS results in vasodilation and controls vascular resistance, platelet adhesion and aggregation, leukocyte‐to‐endothelium interaction, and the maintenance of BBB integrity [36].
Several reports have indicated significant nervous system morbidity due to viral, bacterial, fungal, and parasitic infections (review [39]). During a systemic response to infections, cytokines, chemokines, and damage‐associated soluble mediators of systemic inflammation can gain access to the CNS via blood flow [40]. These mediators can access the brain tissue after the disruption of the BBB. The presence of proinflammatory mediators leads to a disturbance of neuronal and glial homeostasis, with subsequent cognitive and behavioral manifestations that are common during acute infections (anorexia, malaise, depression, and decreased physical activity) and are collectively known as sickness behavior [40]. Although sickness behavior manifestations are transient and self‐limited, the cognitive and behavioral changes can become permanent or long‐lasting under a persistent systemic inflammatory response. For example, cognitive decline is a common consequence in sepsis and cerebral malaria survivors, as found in both clinical and experimental approaches.
Under healthy conditions, the main cell types that are present in the brain are neurons, oligodendrocytes, astrocytes, and microglia. Neurons connect to each other through long axonal processes with synapses to transmit electrical/chemical signals, thereby generating memory and emotions that are associated with learning, and to control organ and systemic functions. Oligodendrocytes support axons with myelin sheaths. Astrocytes interact with blood vessels to form the BBB and maintain neuronal synapses. Microglia form long processes to phagocyte apoptotic cells and prune inactive synapses without inducing inflammation while maintaining a type of surveillance of neurons. Systemic inflammatory conditions result in the disruption of the BBB and the efflux of proinflammatory cytokines/chemokines as well as pathogen‐associated molecular patterns (PAMPs) and danger‐associated molecular patterns (DAMPS), which together activate glial cells. This results in an inflammatory environment due to the release of cytokines/chemokines and reactive oxygen/nitrogen species that exert direct and indirect neuronal cytotoxic effects [40, 41]. Oligodendroglial myelin sheaths can be affected, thereby leading to axonal degeneration. Astrocytosis leads to reduced BBB and synaptic maintenance. Microgliosis results in a proinflammatory microglial phenotype with reduced tissue maintenance functions [41, 42]. Neuronal cells can develop an excitotoxicity process due to excessive glutamate in the synaptic cleft and subsequent extra‐synaptic NMDA receptor activation that results in a subsequent increase of Ca2+ efflux in neuronal cells and the activation of proteins calpain 1 and neuronal nitric oxide. This results in mitochondrial dysfunction and oxidative damage by reactive oxygen and nitrogen species [43]. Together, these mechanisms lead to neuronal death, thereby contributing to long‐term cognitive decline, which has been shown to be a consequence of several infectious diseases.
As shown in Figure 2, the gaseous signaling molecule NO has a variety of cellular functions, including neurotransmission, regulation of blood‐vessel tone, and immunity. Under pathological conditions, free radicals may deplete NO produced by eNOS through the formation of ONOO−, thus decreasing the vascular bioavailability of NO, which results in BBB dysfunction. This ultimately results in endothelial damage, edema development, and hypoxia. Furthermore, the NO produced by iNOS in glial cells or by nNOS under excitotoxic process can form with free radicals (particularly O2−) ONOO− and produce several deleterious effects on tissue, such as through tyrosine nitration and cysteine oxidation in various proteins. These free radicals can further decompose into highly toxic‐free radicals, such as NO2• and •OH (as reviewed by [44]).
Different steps in the NO signaling cascade under physiological/pathological conditions in the brain. During long‐term potentiation, NOS1 or neuronal NOS (nNOS) catalyze the NO synthesis after the activation of the NMDA receptor by Ca2+. Under excitotoxic conditions, excessive Ca2+ leads to nNOS hyperactivity, whereas excessive NO production can combine with superoxide to form peroxynitrite, which is responsible for tissue damage due to several biological effects, including blockage of the eNOS pathway and BBB impairment. NO is synthesized following the transcriptional expression of a Ca2+‐independent NOS2 or iNOS isoform in glial cells (astrocytes and microglia) after cytokine exposure, thereby contributing to neuroinflammation and tissue damage in the brain. Intracellular Ca2+ activates NOS3 or eNOS to release NO from brain microvessels. This NO binds to soluble guanylyl‐cyclase (sGC) receptors, which triggers a cGMP‐dependent pathway and interacts with its downstream mediators of the physiological regulation of vasodilation and vascular resistance, platelet adhesion and aggregation, leukocyte‐endothelial interaction, and BBB integrity maintenance. Images:
Nitric oxide, as described above, is a key molecule in the regulation of physiological brain homeostasis. Nitric oxide is synthetized by neuronal vessels (eNOS), by neurons (nNOS) under physiological/pathological
Our group and others have shown that eNOS is impaired during systemic infection, which leads to brain microcirculation dysfunction [46–48]. We showed that during different infectious diseases, there is a functional capillary rarefaction (Figure 3) that can be caused by the impairment of endothelial NO production by a reduction of eNOS activity or by reduced levels of the enzyme cofactor tetrahydrobiopterin—BH4 [49].
Photomicrography from intravital microscopy showing capillary impairment (red arrows) under healthy (A) and infectious conditions (B) malaria, (C) sepsis, and (D) Chagas’ disease [
Vascular function can be evaluated by the vasodilator response of cerebral arterioles to acetylcholine (Ach). Our group used intravital microscopy to evaluate the response to Ach in sepsis and Chagas’ disease model. The vasodilation‐to‐Ach test is directly related to the availability of endothelium‐derived NO generated from l‐arginine by the action of endothelial NO synthase (eNOS). The diffusion of NO to vascular smooth muscle cells and the activation of guanylyl‐cyclase resulted in cGMP‐mediated vasodilation. However, the vasoconstrictive response to Ach results from a direct muscarinic smooth muscle effect [50]. This vasoconstrictive effect can lead to the slow delivery of oxygen to brain tissue, generating hypoxia and increased glycose consume by glycolytic pathway to generate ATP for neuronal functioning. Consequently, mitochondrial function is compromised by low O2 concentration [51].
In both sepsis and Chagas’ disease models, we observed a vasoconstrictive response to Ach. One mechanism of eNOS “uncoupling” from the reduction of NO production and ROS generation involves the oxidative degradation of the cofactor BH4 (tetrahydrobiopterin), especially by peroxynitrite (ONOO−), which is produced in association with superoxide and nitric oxide. Several studies have shown that there is an increase in impaired eNOS‐derived oxidative stress in brain tissue exposed to systemic infection, NO consumption and capillary dysfunction [46, 47, 52, 53].
Interestingly, in experimental models of malaria [48] and sepsis (Reis et al., submitted) blood flow was recovered by treatment with statins. As reviewed by Giannopoulos et al. [54], statins are shown to enhance eNOS expression and can contribute to the restoration of brain capillary function.
Resident glial cells in the CNS (i.e., astroglia and microglia) express inducible nitric oxide synthase (iNOS) and produce high levels of NO in response to a wide variety of proinflammatory and degenerative
Data from our group show that the absence of the iNOS enzyme (knockout) or treatment with iNOS‐specific inhibitors (e.g., aminoguanidine) has a beneficial effect on the prevention of cognitive impairment (unpublished data) in experimental cerebral malaria. This could be due to the reduced production of the peroxynitrite radical and the subsequent reduction of tissue damage. Other studies are being conducted to clarify the impact of the synthesis of nitric oxide by iNOS in infectious diseases and in the development of cognitive decline. Weberpals et al. also observed that iNOS gene deficiency prevents cognitive decline in addition to promoting a reduction in gliosis (astrocytes and microglia), proinflammatory cytokines TNF‐α and IL‐1β release, and reduction of synaptic dysfunction in sepsis model [58].
The NMDA receptor is a key regulator during glutamatergic long‐term potentiation (LTP) response. During physiological conditions, glutamatergic ionotropic (e.g., kainate, NMDA, and AMPA) and metabotropic receptors (mGlut) are activated, delivering Ca2+ into neuronal cells and resulting in depolarization and the triggering of mitogen‐activated protein kinase (MEK)/extracellular signal‐regulated kinase (ERK) and phosphatidylinositol 3‐kinase (PI3K) signaling pathways. This then activates phosphoinositide‐dependent kinase 1 or 2 (PDK1/2), Akt, and mammalian target of rapamycin (mTOR) downstream signaling [59]. Additionally, calcium‐dependent kinase II (CAMKII) is rapidly activated and all events together lead to the activation of transcription factors (e.g., CREB) and an increase in the synthesis of neurotrophic factors (e.g., BDNF) and proteins associated with the long‐term potentiation (LTP) process.
Despite the major activity of NMDA receptors in LTP, several reports have related this receptor with excitotoxicity, which is a neurodegenerative process. This process has been associated with a different class of NMDA receptor: the extra‐synaptic receptor. As reviewed by Parsons and Raymond, synaptic NMDA (which expresses the subunit GlutN2A) is associated with LTP, whereas extra‐synaptic receptors (which express the subunit GlutN2B) is associated with excitotoxicity and cell death [42]. NMDARs recruit the calcium‐dependent enzyme nNOS via PSD95 (postsynaptic density: membrane‐associated guanylate kinase (MAGUK) scaffolding protein located in neural postsynaptic densities), which is also associated with the LTP process. This is considered a key contributor to excitotoxicity lesions in both stroke and neurodegenerative diseases [60]. nNOS is activated by calcium/calmodulin signaling and is PSD95 protein‐dependent [60]. During excitotoxicity, the activation of NMDA enhances intracellular calcium, leading to nNOS activation and NO production. Additionally, excessive intracellular calcium activates calpain 1, which then disrupts mitochondrial function, thereby triggering the intrinsic apoptotic pathway by releasing cytochrome C and activating apoptosomal protein complex [61]. NO can combine with superoxide, which results in peroxynitrite formation and cellular damage. Peroxynitrite can disturb cellular function by the nitration of proteins, which reduces or eliminates protein function, as described earlier, and by DNA damage via the activation of poly (ADP‐ribose) polymerase 1 (PARP‐1). The impact of PARP‐1 on intracellular concentration of its nicotinamideadenine dinucleotide substrate (NAD), creates a bioenergetic imbalance that culminates with ATP depletion, thereby triggering necrotic neuronal death [62, 63]. In addition, NO can drive the retraction of the synaptic button via the activation of small GTPase RhoA/ROCK signaling through a paracrine/retrograde‐signaling pathway [64]. Taken together, these events could contribute to neuronal dysfunction and death associated with cognitive decline.
The roles of NO in neuronal damage following insults, such as hypoxia, traumatic brain injury, and ischemia, have been well established. Recent evidence has implicated an imbalance of ROS and NO signaling in neurodegenerative disorders, such as Alzheimer\'s disease and Parkinson\'s disease, and in cognitive impairments associated with normal physiological aging [65–67]. Whereas mild oxidative/nitrosative (nitric oxide (NO)‐related) stress mediates normal neuronal signaling, the accumulation of free radicals is associated with neuronal cell injury or death.
As described above, NO from eNOS modulates blood flow in the brain, and its impairment could be associated with hypoxic events in the brain. Several degenerative and infectious diseases relate hypoxia to neuronal dysfunction and cognitive decline. Using partial eNOS knockout mice model, Tan et al. [68] showed that the development of spontaneous thrombotic cerebral infarction is followed by amyloid protein deposit and cognitive decline. Cognitive decline is a major cause of disability in stroke survivors [69]. We have shown that microvascular impairment in malaria, sepsis, and Chagas’ diseases may occur in response to other infectious agents [46–48]. Cerebral metabolism is dependent upon the glucose and oxygen that are delivered by blood, and it is clear that alterations in endothelial function can disrupt neuronal functions. Additionally, activation of endothelial cells by systemic cytokines, PAMP/DAMP and prooxidant molecules can contribute to eNOS dysfunction [70], blood flow disturbance and neuronal dysfunction, which subsequently results in cognitive decline.
The activation of glial cells that may be related with systemic inflammation associated to host response to pathogens can activate inducible isoforms of iNOS and subsequently generate cellular damage via the generation of peroxynitrite by the combination of NO and superoxide radicals. In this way, the induction of iNOS may result in the development of cognitive impairment [71]. Experimental models of sepsis [58] and malaria (unpublished data) have shown that the inhibition of iNOS has a beneficial effect on the central nervous system, particularly by abolishing cognitive decline.
The main enzyme target in the central nervous system seems to be nNOS. The NO generated by nNOS controls the release of neurotransmitters and is involved in synaptogenesis, synaptic plasticity, memory function, and neuroendocrine secretion. However, the overproduction of NO during NMDA‐excitotoxic events can lead to neuronal death and directly impact the cognitive function.
Death pathways are activated in mouse brains during experimental model of sepsis and malaria [72, 73]. Additionally, reduced levels of neurotrophic factors, impairment of neurogenesis, and synaptic dysfunction were observed [74–78]. However, the role of excitotoxicity and nNOS delivery during infectious diseases and long‐term cognitive impairment is not yet clear. Neuroinflammation can also induce cell damage/death, and the modulation of the activation of glial cells has been suggested to prevent neuronal damage and cognitive decline. Cognitive impairment is prevented by antioxidants and statin treatment [48, 53, 79], which suggests that the control of oxidative or inflammatory damage is also efficient to avoid cognitive decline.
NO is a key molecule involved in the regulation of CNS function in health and disease (Table 1). The impairment of enzymatic activity or the overproduction of NO under inflammatory/excitotoxic conditions can contribute to neurological sequela during systemic‐infectious diseases (Figure 3). The NO synthase complex can be considered a target of pharmacological intervention focusing on the prevention of cognitive sequela; however, this field requires further studies.
NOS isoform | Physiological effect on CNS | Pathological effect on CNS |
nNOS | Learning and memory | ↑—Neuronal death by excitotoxicity |
eNOS | Vasodilation and increased blood flow | ↓—Hypoxia |
iNOS | Sleep [ | ↑—Tissue damage |
Nitric oxide synthase enzymes functions on health/pathological conditions.
Red cells (RCs), also called as erythrocyte, are the most abundant cells in the body and highly specialized in gas transportation [1]. RCs deliver oxygen from the lungs to all body tissues and carry carbon dioxide to the lungs. For the delivery of the gases, RCs circulate through blood vessels to the whole body without being trapped inside narrow capillary vessels (5–10 μm in diameter) which are smaller than the size of RCs [2]. Also, RCs do not get attacked by immune system such as mononuclear phagocytic system (MPS) and complement system (CS) [3, 4]. The unique characteristics of the RCs come from specialized microstructure of RC. The microstructure of RC has a biconcave disc-like shape and is fully packed with hemoglobin instead of nucleus and intracellular organelles. Also, various membrane proteins and carbohydrates are embedded in the cell membrane which characterizes intrinsic functionalities of RCs [5]. The biconcave disc-like shape maximizes the surface area of the cell, which increases the gas exchanges between internal and external gases. Hemoglobins are oxygen-transport metalloproteins that bind gases such as oxygen and carbon dioxide. Especially, membrane proteins of RC are responsible for numerous characteristics such as permeability to specific molecules (e.g., glucose, urea, and gases), immune evasive properties, unique biconcave disc-like structure, flexibility, and deformability [4, 6]. Recently, it is reported that membrane proteins of RC can be utilized by manipulating the cell membrane [7]. The RC membrane (RCM) inside the whole blood of mice or human contains membrane proteins, which were extracted and purified. Accordingly, intriguing researches were conducted together. For example, just like RC does, RCM-coated nanoparticles showed long circulation in the blood by evading immune responses such as MPS and CS [7, 8]. Also, RCM-coated glucose sensors showed high permselectivity to glucose [9]. As a result, the sensor was barely affected by interfering molecules such as saccharides and antioxidants. Likewise, the utilization of the functionalities of membrane protein of RC advances nanobiotechnology in the field of drug delivery system and biosensor. In this chapter, we investigate the various membrane proteins expressed on RC and its functionalities. The techniques for extraction and functionalization of cell membrane have been researched. Also, we discuss about the application of RCM functionalization for the last decade.
\nMembrane proteins are essential components allowing specific functionalities for cells. There are three categories classified by its function. Membrane proteins perform as receptors, transporters, and cell adhesion molecules. Table 1 represents major membrane proteins on RCM classified by their function [5].
\nProtein | \nGene | \nFunction | \n
---|---|---|
\n | \n | |
CD55 (aDAF) | \nCD55 | \nDecay-accelerating factor that prevents the activation of complement system | \n
CD59 | \nCD59 | \nbMAC-inhibitory protein that prevents complement membrane attack complex | \n
\n | \n | |
AE1 (band 3) | \nSLC4A1 | \nAnion transporter | \n
RhAG | \nRhAG | \nAmmonia transporter | \n
Nucleoside transporter | \nSLC29A1 | \nNucleoside transporter | \n
Urea transporter | \nSLC14A1 | \nUrea transporter | \n
Glucose transporter | \nSLC2A | \nGlucose transporter | \n
\n | \n | |
CD47 | \nCD47 | \n“do not eat me” signal protein that interacts with cSIRPα to inhibit phagocytosis | \n
Various membrane proteins in RCs [5].
DAF, decay-accelerating factor.
MAC, membrane attack complex.
SIRPα, signal regulatory protein alpha.
Membrane receptors consist of CD55 and CD59; transporters consist of AE1, RhAG, nucleoside transporter, urea transporter, and glucose transporter; cell adhesion molecule consists of CD47.
Membrane receptors are one of integral membrane proteins. They mediate cell signaling via binding extracellular molecules. Specifically, membrane receptors allow communication between the cell and external environment. Hormones, cytokines, cell adhesion molecules, and immunoproteins are examples of the extracellular molecules. The ligand bound of the membrane receptor may induce changes in the metabolism or activity of the cell. In RC, CD55 (decay-accelerating factor) and CD59 are well-known membrane receptors which inhibit CS preventing hemolysis (Figure 1) [10]. In detail, CS is composed of proximal and terminal complement (Figure 2) [4]. The proximal CS has three pathways converged at the step of complement component 3 (C3) activation. The terminal complement is initiated with complement component 5 (C5) and ended with formation of membrane attack complex (MAC). In this cascade, CD55 inhibits C3 activation by deactivating C3 convertase [11]. CD59 inhibits terminal complement activation by preventing the formation of MAC that starts with the activation of C5 [12]. The absence of CD55 and CD59 may lead to hemolysis of RC via complement activation [4].
\nHemolysis mechanism of paroxysmal nocturnal hemoglobinuria (PNH) via the complement system [
Complement system signal cascade [
Transporters are involved in the movement of specific molecules or ions across cell membrane. The proteins are involved in the movement of molecules by active transport or facilitated diffusion. It is revealed that anion, gas, nucleoside, urea, and glucose transporters are expressed on the RC. In detail, (AE1, also called band 3) is responsible for mediating the exchange of chloride ion with bicarbonate (HCO3ˉ) across RCM [13]. Rh-associated glycoprotein (RhAG) is a gas transporter which permeates carbon dioxide [1]. Nucleoside transporter mediates the transport of nucleoside substrates like adenosine [14]. Urea transporter is specialized in urea transportation, which is activated by antidiuretic hormone (vasopressin) [15]. Glucose transporter (GLUT) is a uniporter that transports glucose toward intracellular orientation (Figure 3) [16]. GLUT is an essential protein for glucose uptake of the cell by catalyzing facilitative diffusion. Especially, RC expresses a large number of GLUT compared to other cells because the cell lacks mitochondria and the energy is produced by glycolysis of glucose [17].
\n(a) Overall structure of human glucose transporter-1 (GLUT1) and (b) working model for GLUT1 [
Cell adhesion molecules interact with membrane receptors of various cells. RC has CD47 as a cell adhesion molecule [18]. CD47 belongs to the immunoglobulin superfamily and sends a “
The cocrystal structure shows human CD47 (hCD47) with human signal regulatory protein α (hSIRPα). The left panel depicts that the occurrence of phagocytosis depends on the reaction between hCD47 and hSIRPα [
RC can easily be extracted from whole blood of mice or human. Normally, the whole blood is extracted at vacutainer tube (evacuated tube) containing anticoagulant such as heparin, citrate, or ethylenediaminetetraacetic acid (EDTA) according to the purpose (Table 2). Heparin collection tubes are preferred for peripheral blood in cytogenic studies. Heparin activates antithrombin III which deactivates thrombin and serine endopeptidase, which are essential enzymes for coagulation [20]. Citrate collection tubes are employed for blood transfusion and coagulation assays because citrate reversibly binds to calcium which is an essential molecule in many steps of coagulation cascade [21]. EDTA collection tubes are usually used for complete blood count (CBC) test because EDTA is a strong anticoagulant that irreversibly binds to calcium [22]. Since coagulation requires RC to form blood clot, EDTA collection tubes are mostly used for RC extraction [7, 8, 23].
\nAnticoagulant | \nUsage | \nMechanism | \n
---|---|---|
Heparin | \nCytogenetic studies | \nActivate antithrombin III which deactivates serum clotting factors (factors aIIa and bXa) | \n
Citrate | \nCoagulation assays, blood transfusion | \nBind to calcium reversibly (not as strong as EDTA) | \n
Ethylenediaminetetraacetic acid (EDTA) | \nmolecular genetic studies, complete blood counts | \nStrongly bind to calcium irreversibly. The absence of calcium | \n
Vacutainers with various anticoagulants.
Factor IIa, thrombin.
factor Xa, serine endopeptidase.
The procedure for extracting RC from whole blood is as follows [23]. Whole blood withdrawn from mice or human is centrifuged at 800–1000 g for 5 min at 4°C in order to remove the plasma and the buffy coat. The resulting sediment is washed three times with ice-cold 1× PBS to remove blood proteins adsorbed on RCs. To extract cell membrane from RCs, hypotonic treatment, homogenize, or sonication is conducted for hemolysis. Hypotonic treatment is the most convenient hemolysis procedure without disruption of membrane and membrane proteins. Washed RCs are suspended in 0.25× PBS for 20 min at 4°C. As hemolysis progresses, hemoglobin is released from RCs, and RC ghosts (empty cell membrane without cytoplasmic contents) are formed [24]. As a result, RC ghost can be verified with phase contrast microscope. To remove the hemoglobin, hemolyzed solution is centrifuged and washed. Then the RCM is collected with light pink pellet. The resulting RCM concentrate is stored in −70°C before use.
\nCell membrane coating technology comes from phospholipid manipulation technique which forms liposome and solid-supported lipid bilayer because the phospholipids are the main component of cell membrane. Although the phospholipid manipulation technique was developed quite a while ago, cell membrane coating techniques on nanoparticles were first reported in 2011 (Figure 5) [7]. Researchers prepared RCM-coated nanoparticles by RCM vesicle-nanoparticle fusion [25, 26]. Specifically, the extracted cell membrane was adequately diluted (membrane extraction was described in Section 3.1.). For the membrane vesicle derivation, outer forces are applied to the diluted membrane. Sonicating the membrane is the easiest way to make membrane vesicle, but it is hard to regulate the size of the vesicle. Alternatively, extrusion methods can control the size of the membrane vesicle by porous polymer membrane with various pore sizes. Next, membrane coating onto nanoparticles is conducted with the same procedure to vesicle formation (i.e., sonication or extrusion). In detail, the prepared membrane vesicles are mixed with nanoparticles. Then the sonication or extrusion of the mixture can lead to the coating of membrane onto the nanoparticles by the principle of vesicle fusion.
\nThe schematic illustration of the preparation of RBC membrane-coated polymeric nanoparticles [
The cell membrane coating on solid surface is similar to that on nanoparticles described above. The coating procedure is based on vesicle fusion method (Figure 6) [27]. The only different procedure for solid surface coating is that thermal energy is employed instead of mechanical energy (i.e., sonication or extrusion) [9, 28]. Specifically, the cell membrane vesicles with adequate concentration were placed on solid surface and incubated for 45 min at 50°C. The thermal energy induces the membrane vesicle to collide and fuse onto the solid surface. It is noted that the temperature for vesicle fusion should be lower than the denaturation temperature of proteins to avoid the deactivation or misfolding by high thermal energy [29].
\nFusion of a lipid vesicle on solid surface [
RCM-coated nanoparticles, also called RC-camouflaged nanoparticles, have been developed for drug delivery system since they were devised by Zhang and his group in 2011. It was found that immune evasive properties of RCM-coated nanoparticles are superior to conventional nanoparticles. The membrane proteins confer the advantages of the immune avoidance properties described in Section 2. RCM coating has been applied to various core nanoparticles such as gold, poly(lactic-co-glycolic acid) (PLGA), silica, and iron oxide nanoparticles [30]. Also, RCM can be utilized as permselective filter for glucose biosensor taking advantage of GLUT on RCM [9].
\nIn drug delivery system related with nanomaterial, long-term circulation of nanoparticles in vivo is one of the most important characteristics because various immune responses clear the foreign molecules in the body and blood [31]. Especially, MPS and CS are major immune systems eliminating drug delivery carriers. Conventionally, to evade the immune systems, the drug carriers are functionalized with polyethylene glycol (PEG) which slows clearance in blood and avoids non-specific binding of blood proteins [32, 33]. In our body, however, there is an anti-PEG immunological response which removes PEGylated nanoparticles [34]. By contrast, the RCM-coated nanoparticles showed prolonged circulation in blood. The result is exactly attributed to membrane receptors and cell adhesion molecules, which were abundant and diverse on RCM. In this regard, the immune evasive properties of RCM-functionalized nanomaterials have great potential as clinical drug delivery carriers. In particular, it is researched that the RCM-functionalized nanoparticles showed good dispersion stability in serum and great biodistribution in mice model up to 72 h (Figure 7) [7]. Indeed, it is demonstrated that the RCM inhibits macrophage uptake. RCM-coated gold nanoparticles showed ~4 times higher immune evasive properties than bare gold nanoparticles [8].
\nBiodistribution of RCM-coated gold nanoparticles in mice [
In biosensors, not only sensitivity but also specificity (selectivity) is important because numerous molecules coexist in the biological samples that may interfere the detection [35]. For example, blood contains ions, saccharides, proteins, and blood cells which hinder accurate glucose detection. Enzymatic glucose biosensors, most widely used, employ glucose oxidase or glucose dehydrogenase for selective detection of glucose. However, the enzymes react with glucose and other similar structured molecules (mono- and disaccharides) such as fructose, galactose, and maltose in blood. For this reason, glucose sensors are interfered by the molecules. It is reported that RCM which has glucose transporter was employed as glucose-selective permeable membrane by taking advantage of GLUT (Figure 8) [9]. The RCM-coated sensor showed high selectivity to glucose compared to uncoated sensor. In detail, the uncoated sensors are highly affected by the increment of interfering molecules (e.g., ascorbic acid, uric acid, and galactose), whereas the RCM-coated sensors exhibit consistency in glucose detection. In particular, RCM-coated sensor showed that the signals of glucose with interfering molecules barely change from that of glucose without interfering molecules (Figure 9) [9].
\nSchematic illustration of RCM-coated glucose sensor [
Selectivity test of RCM-coated glucose sensors under competitive interactions between glucose and each interfering molecule [
The RCM has various types of membrane proteins such as membrane receptor, transporter, and cell adhesion molecules. Each type of membrane proteins is full in potentials to be applied in various fields such as drug delivery system and biosensor. The well-evolved functionality of membrane proteins can be easily utilized by coating the RCM on nanomaterial and solid surface of sensors. Currently, drug delivery system is the major field of RCM application because the membrane can confer the immune evasive properties of RCM to the nanomaterials. In the future, it is expected that the RCM will be increasingly applied in development of highly selective biosensors utilizing various transporters on RCM.
\nThis work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (No. NRF-2016R1A2B4010269, NRF-2017R1A6A3A11034311 and NRF-2018M3C1B7020722). This material is also supported by the Ministry of Trade, Industry and Energy (MOTIE, Korea) under Industrial Technology Innovation Program (No.10079316). Gyudo Lee is thankful for the financial support by Korea University Grant.
\n"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
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\\n\\nLicense
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\\n\\nOA Publishing Fees
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\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
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\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{paginationCount:5,paginationItems:[{id:"11672",title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",hash:"c00855833476a514d37abf7c846e16e9",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 6th 2022",isOpenForSubmission:!0,editors:[{id:"14794",title:"Prof.",name:"Murat",surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11674",title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",hash:"5d7d49bd80f53dad3761f78de4a862c6",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 6th 2022",isOpenForSubmission:!0,editors:[{id:"238047",title:"Dr.",name:"Gaia",surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11670",title:"Chitin-Chitosan - Isolation, Properties, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11670.jpg",hash:"69f009be08998711eecfb200adc7deca",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 26th 2022",isOpenForSubmission:!0,editors:[{id:"176093",title:"Dr.",name:"Brajesh",surname:"Kumar",slug:"brajesh-kumar",fullName:"Brajesh Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11673",title:"Stem Cell Research",coverURL:"https://cdn.intechopen.com/books/images_new/11673.jpg",hash:"13092df328080c762dd9157be18ca38c",secondStepPassed:!1,currentStepOfPublishingProcess:2,submissionDeadline:"July 13th 2022",isOpenForSubmission:!0,editors:[{id:"203598",title:"Ph.D.",name:"Diana",surname:"Kitala",slug:"diana-kitala",fullName:"Diana Kitala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"12215",title:"Cell Death and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/12215.jpg",hash:"dfd456a29478fccf4ebd3294137eb1e3",secondStepPassed:!1,currentStepOfPublishingProcess:2,submissionDeadline:"July 29th 2022",isOpenForSubmission:!0,editors:[{id:"59529",title:"Dr.",name:"Ke",surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82212",title:"Protein Prenylation and Their Applications",doi:"10.5772/intechopen.104700",signatures:"Khemchand R. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. 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