Electrospinning parameters affecting fiber morphology.
\r\n\tCKs have crucial roles in various viral infections such as influenza, hepatitis B virus (HBV), hepatitis C virus (HCV), viral meningitis, human immunodeficiency virus (HIV), and SARS-CoV-2.
\r\n\tCKs mediate the directing of the transport of leukocyte cells into the tumor microenvironment to generate the host response against cancer. CKs can directly modulate tumor tissue expansion by inducing the proliferation of cancerous cells and inhibiting their apoptosis. They can also indirectly modulate the growth of tumor tissue through the effects of CKs on tumor stromal cells, by inducing the release of growth and angiogenic factors of cells that make up the tumor microenvironment.
The augmented number of dementia patients has been dramatic due to the aging of society in advanced countries. Alzheimer’s disease (AD) is the most common type of dementia and accounts for more than half (50–70% depending on the reports) of all dementia. AD is characterized by a gradual onset by developing neuronal damage and continuing cognitive decline related to stress-induced cell damage in the patient’s brain [1], which ultimately causes significant impairment to social and occupational functions. The mean duration from the onset of clinical symptoms to the death of the patient has been reported to be approximately 8.5 years [2].
\nAD is defined by the presence of plaques and tangles in the brain, thus the gold standard for the diagnosis of Alzheimer’s disease (AD) is set by means of the histological examination of brain tissue at autopsy, which is usually done after a patient has died, or, rarely, following brain biopsy. On the other hand, clinical diagnosis of AD during life has been performed with a sensitivity ranging from 70.9% to 87.3% and specificity from 44.3% to 70.8% [3]. It was also reported that dementia is often overlooked in community care settings [4].
\nFor objective diagnostic analysis, several biomarkers are available. The reliable biomarker candidates for AD include brain imaging studies using magnetic resonance imaging (MRI) or positron emission tomography (PET), and proteins in cerebrospinal fluid (CSF). MRI is utilized for structural imaging, PET for molecular imaging of amyloid deposition and fluoro-deoxy-D-glucose (FDG)-PET for metabolic imaging, while measurements of amyloid peptide (Aβ) and TAU protein in cerebrospinal fluid (CSF) are used for quantitative analysis. However, structural changes measured by MRI only become apparent in the late stage of AD. Moreover, structural MRI and FDG-PET images are not direct measures of the core pathological hallmarks of AD. PET imaging is relatively expensive and limited in availability. CSF Aβ and TAU might be nonspecific for AD depending on each case [5]. At present, it can be stated that the most well-characterized and validated biomarkers are Aβ and TAU in CSF: the decrease in Aβ with 42 amino acid residues (Aβ42) and increase in TAU and phosphorylated TAU (P-TAU) has been observed in AD patients in several of studies [6].
\nAn alternative method to the invasive CSF collection and expensive specialized facilities for diagnostic imaging is most desirable. Thus, plasma biomarkers have raised expectations because blood sampling is a much less invasive procedure. Blood-based biomarkers have the potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Due to the fact that preanalytical processing shows the largest variation in laboratory testing, there are currently no available standardized preanalytical guidelines. In this review, the primary focus is on the fluid biomarkers, especially blood plasma protein biomarkers, as indicators of AD development together with our study on results of a specific blood plasma candidate.
\nDiagnostic markers are anticipated to be present in secreted proteins followed by a result of cell damage in pathological states. Although CSF sampling by lumbar puncture definitely is known to be an invasive procedure, at present CSF is probably the most informative fluid in biomarker detection for neurodegenerative disease prognosis [7]. CSF has direct contact with the brain, and it does not easily escape from the brain owing to the fact that the blood-brain barrier (BBB) is tightly regulated. In general, if a biomarker candidate is identified in CSF, its possibility as a true biomarker for brain-specific activities, as well as disease pathology, would be considered to be more promising compared with any other body fluid biomarker candidate.
\nIt has been demonstrated that senile plaque formation and neuronal loss precede clinical onset of Alzheimer’s disease [8]. Senile plaques are polymorphous and comprise Amyloid β peptide (Aβ), a proteolytic product of amyloid precursor protein (APP) that accumulates in the brains of AD patients. Several species of Aβ peptide depending on the cleavage sites on APP have been identified in the body fluid. APP processing consists of initially proteolysis by β-secretase and then by β-secretase, which leads to the formation of Aβ peptides with 38–43 residues [9]. Of these, Aβ42 with 42 amino acid residues is the most remarkably focused due to its toxic effect. Aβ42 is highly hydrophobic and forms oligomers and fibrils that accumulate as extracellular plaques, which correlates inversely with plaque pathology [1, 10]. Attenuated activity of Aβ-degrading catabolic enzymes including neprilysin and insulin-degrading enzymes with age or abnormal production of Aβ due to gene mutation(s) of related proteins such as on APP have been identified, which in turn leads to the accumulation of Aβ42 in the brain tissue [11].
\nOn the other hand, TAU that is an intracellular protein, is believed to be involved in filament stabilization, and has been shown to aggregate to form filaments in neurons. In normal individuals, only a low concentration of TAU is present in CSF. The function of TAU is tightly regulated by a number of posttranslational modifications possibly due to phosphorylation at serine and threonine residues. Several studies have suggested that hyperphosphorylation and formation of neurofibrillary tangles (NFTs) is the pathophysiological phenomenon of the development of AD [12]. It is remarkable that functional loss of TAU following hyperphosphorylation, the dissociation of TAU from microtubule and subsequent polymerization into insoluble paired helical filaments (PHF) could result in the loss of axonal integrity in the neuronal cells [13, 14]. NFT formation and neuronal degradation is an essential part of AD pathology.
\nDue to significant disruption of the neuronal architecture, the TAU and its hyperphosphorylated form (P-TAU) could appear in CSF [15]. Therefore, the phenomenon of increased levels of TAU and P-TAU in CSF represents well with the onset of neurodegeneration in AD. The total TAU (t-TAU) concentration in CSF has been measured by the method of ELISA using monoclonal antibodies against all TAU isoforms. Several groups have indicated that t-TAU concentration in CSF of AD patients is significantly higher than control [15, 16]. On the other hand, the attenuation of the amount of Aβ42 in CSF has been noted due to accumulation in the brain [17]. Thus, decrease in level of Aβ42, increase in t-TAU and P-TAU have been utilized as CSF biomarkers contributing to the diagnosis of AD [18]. In addition, the development of imaging biomarkers has provided evidence of an ongoing AD pathophysiological process.
\nThe Aβ ratio (Aβ40 to Aβ42) in the AD group was significantly increased compared with that in the normal control group, the non-AD type dementia group, and the other neuronal disease group [19]. For the enhancement of the diagnostic relevance of AD, AD index that is calculated by multiplying TAU level by the Aβ ratio was shown to be useful for discrimination of AD patients from healthy controls with good sensitivity and specificity [19].
\nIt was reported that low CSF level of Aβ42 appeared to predict conversion of mild cognitive impairment (MCI) to AD, while a decrease in Aβ42 level has also been observed in other neurodegenerative disorders [20]. Furthermore, it was shown that levels of TAU and P-TAU at Ser181 (P-TAU181) in CSF, but not Aβ42, correlated oppositely with whole brain volume in the early stage of AD, whereas levels of CSF Aβ42, but not TAU or P-TAU181, was positively correlated with whole brain volume in nondemented controls [17].
\nIt is thought that the production and accumulation of unfavorable Aβ species proceeds over time as the disease progresses. Abnormal activity by the Aβ species is initiated before pathological change and reaches a plateau before the clinical symptoms appear. Thereafter, elevation of TAU and P-TAU that are the biomarkers for neuronal injury, dysfunction, and degeneration, become apparent in the later stage of the disease and correlate with clinical symptom severity [8]. On the other hand, MRI imaging is valuable as it is the last biomarker to show abnormality. As such, MRI retains a closer relationship with cognitive performance later on in the disease compared with other biomarkers. Moreover, none of the biomarkers is stable; that is, the rate of change for each biomarker is not linear over time [8].
\nThe revised guideline for AD diagnosis was released by a working group from the National Institute of Aging in 2011, in which both CSF and imaging biomarkers have been implemented. The new guideline provides evidence of an ongoing AD pathophysiological process, and it is also possible to make a preclinical diagnosis of MCI due to AD [21–23]. AD is classified into three separate stages: preclinical AD, MCI due to AD, and AD with dementia.
\nSince fluid biomarkers of either CSF or blood plasma can serve as objective criteria for dementia diagnosis, this guideline is aiming at early and reliable diagnosis. However, it is clear that at present no single biomarker plays a sufficient discriminatory role in screening for future development of late-onset AD or dementia.
\nCompared with CSF, blood sampling is a less invasive procedure, more easily accessible, and cost reductive, thus the finding of reliable blood biomarkers for AD is being given the highest priority. There has been an increasing research effort to examine the potential biomarkers of AD in blood plasma. However, for blood-based biomarkers, it has to be noted that blood plasma contains several tens of thousands of different proteins. In addition, the range of protein concentrations are extremely varied (attaining to 12 orders of magnitude), and the lower the concentration, the greater the diversity of proteins [24, 25]. Moreover, none of the current methods allows us to directly detect components in the low concentration region [25]. These conditions make it extremely challenging or almost impossible to directly analyze blood, even though possible biomarker candidates are more likely to be present in the areas of low concentration. The change in concentration of the blood components may often be on a very small scale and cover a wide range of both peripheral and central processes. Additionally, the less abundant proteins may be masked by highly abundant plasma proteins such as albumin and immunoglobulin. Therefore, focusing on concentration change of a particular AD-specific marker, which may be in low concentration, can be the most challenging to discover [26, 27].
\nIt was reported that the BBB is disrupted resulting in increased permeability with aging and in AD [28, 29]. It is also thought that this event occurs in the relatively early stage of the aging brain, which is related to increased cognitive impairment. Although the relationship between an analyte found as a biomarker candidate in blood plasma and the behavioral changes in the brain is not easily demonstrated, there is the possibility of a connection due to BBB disruption during the early stage. This might lead one to expect the possible appearance of a brain component in the peripheral blood stream.
\nThe widely accepted CSF biomarker, Aβ peptides, have also been examined in blood, but its concentration in blood plasma is considerably lower than reported in CSF by about 100-fold [30]. Elevated plasma level of either Aβ40 [31, 32] or Aβ42 [33, 34] levels was used as an indicator for the development of AD, while the opposite results [35] or no association at all between plasma Aβ level and AD development [36, 37] were reported. Thus, results based on plasma Aβ as a biomarker have been inconsistent. A low plasma Aβ42 to Aβ40 ratio was utilized for the prediction of future AD [32, 38, 39], while contrary results, reporting a higher ratio [31, 33] in the nascent AD stage patients than the subjects who did not develop AD, and no significant differences were also shown [36].
\nAnother promising candidate of a plasma protein biomarker was identified by means of the proteomic approach. The protein clusterin/apolipoprotein J, which is involved in the clearance of cellular debris and apoptosis, was associated with both hippocampal atrophy and clinical progression [40]. Increased plasma concentration of clusterin indicated the prediction of greater fibrillary amyloid-β burden in the medial temporal lobe and AD patients had increased clusterin messenger RNA in blood. Moreover, in the transgenic AD mouse model (APP/PS1), increased plasma clusterin level, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques were shown [40, 41]. The recent finding is that increased plasma clusterin levels have been associated with increased risk of conversion to AD and the rate of cognitive decline [42]. Clusterin may have a role in Aβ aggregation and clearance [43, 44], and at high concentrations, clusterin may prevent Aβ aggregation through its binding to Aβ. Furthermore, clusterin possesses neurotoxic properties by involvement in noncanonical wnt signaling, which mediates Aβ toxicity [45]. Therefore, clusterin might fulfill different roles. Other plasma biomarker candidates have been reported, such as desmosterol [46], transthyretin [47], chitinase 3-like 1 protein [48], and matrix metalloproteinase 2 [49], which may be associated with AD. Using protein array technology, Ray et al. found 18 signaling proteins in blood plasma that can discriminate AD samples from control subjects with approximately 90% accuracy [50].
\nThe brain-derived proteins present in blood plasma are limited compared with those in CSF due to the presence of the BBB. It is also likely that if potential brain-derived proteins are present in blood plasma, it is conceivable they are considerably diluted in the large volume of plasma and underwent proteolysis and excretion. These possible events make the study more challenging. As mentioned previously, in plasma, there are several tens of thousands of different proteins present at concentrations in the millimolar to femtomolar or lower range. This extremely varied range of protein concentrations in plasma makes it almost impossible to directly analyze low concentration components.
\nTherefore, in our study, instead of direct examination of plasma, we initially utilized a cell culture model, mouse primary culture neuron. After Aβ-treatment, we identified proteins present outside of the cells (culture supernatant), in which Aβ-dependent secreted proteins are expected to be present, using a proteomic approach, and focused on the proteins that were increased by Aβ-treatment, and discovered a biomarker candidate. Ultimately, we verified the potential candidate with animal model (transgenic mice) and human plasma samples (Figure 1).
\nProcess of biomarker identification (our study).
The cytotoxicity due to Aβ42 is thought to be directly linked to neural cell death [1]. Amyloid-dependent neurotoxicity is known to perturb Ca2+ homeostasis in neuronal cells [51]. Possibly, Aβ impairs membrane Ca2+ pumps and enhances Ca2+ influx through voltage-dependent channels and ionotropic glutamate receptors (Figure 2).
\n\nBy focusing on this mechanism, we identified the Ca2+-related protein as a potential biomarker for AD using primary neurons as a cell culture model [52]. Since phosphatidylserine (PS) is flip-flopped and appears in the outer layer of the plasma membrane during the apoptotic process, we focused on PS-binding proteins in the culture supernatant and used a unique method to identify a potential biomarker candidate.
\nThermoresponsive magnetic nanoparticles disperse well in an aqueous solution at a temperature below 10°C and are aggregated and become responsive to magnets at 20°C or higher. In this study, we coated magnetic beads with thermoresponsive polymers (polyethyleneimine) together with myristate and then coated them with PS [52]. We mixed these particles with a culture supernatant in the presence of Ca2+ and collected the PS binding fraction with ethylene glycol-bis(β-aminoethyl ether)-N,N,N\',N\'-tetraacetic acid (EGTA). After running SDS-PAGE, we performed in-gel digestion with trypsin and analyzed the tryptic peptides by reverse-phase liquid chromatography coupled with MALDI TOF/TOF MS spectrometry and performed database analysis for peptide sequencing. From this proteomic approach, about 240 types of proteins were indicated to be increased in the Aβ42-treated sample, compared with the control, suggesting that they were upregulated by Aβ42. From among these proteins, we focused on annexin A5, one of the annexin family proteins that commonly bind Ca2+ and phospholipid. It was shown that annexin A5 was augmented in both the brain and blood plasma in an AD-model mouse (Tg2576 transgenic mice), overexpressing mutant human APP [52]. Technetium-labeled annexin A5 was detectable in the brain after intravenous injection in humans, showing that annexin A5 crosses the BBB [53].
\nAβ-dependent perturbation of calcium homeostasis in AD.
To quantify plasma annexin A5, we previously established the chemiluminescent enzyme immunoassay (CLEIA) system with two clones of monoclonal antibodies against human annexin A5: one clone was conjugated to a glass bead and used for trapping annexin A5 present in the blood plasma; the other clone was labeled with horseradish peroxidase (HRP) and used for quantification of the trapped annexin A5 [52]. The HRP catalyzes the oxidation of a luminol solution that includes a phenol-derivative acting as an enhancer, and produces light. This system was useful to quantify plasma annexin A5 in the range from 0.16 to 20.0 ng/ml [52]. We obtained blood samples from 150 AD, 50 DLB, 14 mild cognitive impairment (MCI), and six depression patients, and 298 healthy elderly individuals from the senior citizen’s clubs. AD patients met NINCDS-ADRDA [54] and DLB patients diagnosed as probable DLB according to the latest consensus diagnostic criteria [55]. Statistical analysis was done using JMP version 9.0.0 (SAS Institute Inc., Cary, NC, USA). The mean response of each experimental group was compared with its simultaneous control by unpaired Student’s
The plasma level of annexin A5 was significantly increased in AD patients compared to that of a control group (
Comparison of plasma levels of annexin A5 in AD, DLB, MCI, depression, and age-matched healthy control.
For quantification of plasma annexin A5, we used a previously established chemiluminescent enzyme immunoassay system with monoclonal antibodies against human annexin A5 [52] (see Section 4.1). Individual plasma annexin A5 concentration is plotted in (A). The probability of either AD, DLB, or MCI can be predicted by a logistic regression model with the plasma level of annexin A5. Receiver operating characteristic (ROC) curves are shown in (B)–(D). The areas under the curve are 86.3%, 83.8%, and 91.6% for AD (B), DLB (C), and MCI (D), respectively. AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; MCI, mild cognitive impairment.
\nAs annexin A5 binds not only phospholipids but also Ca2+, it might have a role in protecting against Ca2+-induced damage by chelating elevated intracellular Ca2+. A defensive role against apoptosis induced by the participation of annexin A5 was also reported, in that annexin A5 plays a role in reducing the toxicity of the amyloidogenic proteins through interaction with them, such as amyloid polypeptides and α-synuclein [56].
\nOn the other hand, dementia with Lewy bodies (DLB) shares clinical and pathological features with other dementia subtypes such as AD, vascular dementia, and Parkinson’s disease (PD), which makes it difficult to distinguish in clinical practice. Lewy bodies are often found in the brains of AD patients. Also, the lack of valid and reliable methods for assessing the core clinical symptoms of both AD and DLB makes its identification even more difficult. We analyzed plasma level of annexin A5 in DLB. When average concentrations of plasma annexin A5 are compared among AD, DLB, and control groups, the values of AD and DLB were significantly higher than healthy control subjects (Figure 3A). Moreover, the ROC analyses showed good separation of patients with either AD or DLB from the control group (healthy volunteers) (Figure 3B and C) [57]. These suggest that annexin A5 is a potential biomarker for both AD and DLB. There is a similarity between AD and DLB. Lewy bodies are often found in the brains of AD patients. The therapeutic agent, acetylcholinesterase inhibitor, is effective not only in AD but also in DLB. From these results, annexin A5 reflects the above-mentioned similarity of AD and DLB.
\nTo examine when annexin A5 becomes elevated during the course of disease development, we analyzed plasma samples from MCI patients (early stage of dementia). Average concentration was significantly higher than for the control group and the level was comparable with that of AD (Figure 3A). The areas under the ROC curve was 91.6% (
We next tracked plasma level of annexin A5 over a 3-year period in late stage AD patients. The plasma level of annexin A5 tended to be unchanged or slightly decreased, which indicates that biosynthesis of annexin A5 might be downregulated during the late stage, due to the progression of neuronal cell damage (data not shown).
\nSince annexin A5 is also expressed in peripheral blood lymphocytes [58, 59], the effect of physical stress (such as osmotic pressure and temperature changes) upon blood cells may induce leakage of annexin A5. In fact, if a prolonged period of time passes (such as 12 h) after collecting blood, prior to centrifugation, the amount of plasma annexin A5 increases compared with a shorter period (such as within 6 h) (data not shown). Therefore, blood samples should be centrifuged within a specified period of time after collection. In our study, we did this within 6 h after blood collection. However, the lack of consistent technical standard for blood sampling in plasma biomarker studies may induce complicated and inconsistent observations depending on the study groups [60]. With respect to some conditions, such as anticoagulant reagent (EDTA or others), needle gauge, and 6-h fasting, standards should be proposed. For plasma preparation, a time limit until plasma separation after blood sampling may be critical to avoid induction of unwanted component leakage. Centrifugation speed (gravity force), duration, temperature, and number of spins, sample storage conditions may also require specification, though most common plasma samples are stored immediately at a temperature of –80°C for long-term storage. There will also be a number of factors that apply to subjects (patients and other participants involved): such as demographics (age, sex, and race/ethnicity), life style, overall health conditions (chronic drug administration, dietary supplements), smoking, and alcohol consumption.
\nSeveral risk factors for AD have been indicated. Genetic factors are increasingly recognized as major risk factors for dementia. The most remarkable factor for AD from numerous studies is the ApoE gene on chromosome 19. ApoE, which is a major component of lipoproteins with 299 amino acid residues, plays a role in the metabolism and redistribution of cholesterol [61]. ApoE constitutes three major common isoforms, designated ApoE2, ApoE3, and ApoE4. ApoE isoforms interact differently with Aβ isoform-specific effects on Aβ-clearance. In ApoE4, domain interaction occurs as a result of a putative salt bridge, leading to tight structural formation. This interaction is unlikely to take place with ApoE2 and ApoE3 [62, 63]. ApoE4 is associated with an increased risk for AD along with early onset of the disease [64]. It was reported that ApoE4 carrier frequency was the highest in AD among AD, DLB, and control groups, and it was also higher in DLB than in the control groups [65]. Other findings have shown that ApoE4 carrier and allelic frequencies were comparable for those with AD and DLB with respect to Japanese subjects [57, 66].
\nRecently, a single nucleotide polymorphism in triggering receptor expressed on myeloid cells 2 (TREM2), an innate immune receptor expressed on the surface of microglia, were associated with both reduced hippocampal volume in healthy older adults and MCI [67, 68]. It was also shown that increased CSF sTREM2 levels were associated with higher CSF total TAU and phospho-TAU181P [69].
\nBiomarkers are usually employed as an indicator of processes related to the onset of a disease, specific disease conditions or response to therapeutic interventions [70]. However, it is clear that at present no single biomarker plays a sufficient discrimination role in screening for future development of late-onset AD or dementia. During development of the disease, the time when each unique biomarker becomes elevated will vary. Therefore, it is imperative to be able to determine when specific biomarkers need to be measured in order to provide timely therapeutic intervention.
\nBlood testing for measuring biomarkers will be easy and widely accepted due to the ease of collection and low cost. Moreover, the increasing availability of large sample sets obtained from a variety of technologies might contribute to diagnosis, prediction, and monitoring the progression of AD [71]. If a standardization of sample collection, standard operating procedures, comprehensive data management, and exchange of scientific findings is established, and if collaborative studies continue to progress, these should lead to a reduction in the variability and fragmentation of data. It is very likely that we may see plasma biomarkers become a reliable indicator for diagnosing AD.
\nBiomarkers of disease presence, subtypes (i.e., endophenotypes), treatment response, and progression are needed to advance therapeutic and preventative opportunities for this rapidly growing health care crisis.
\nIn spite of the fact that reliable biomarkers have been established in CSF, no blood-based biomarker has been fully validated or qualified, even though an increasing number of plasma biomarker candidates have been reported. However, promising candidates have been emerging due to the progress in the field. Longitudinal studies from collaborative research and from the use of a variety of technologies and study designs are expected.
\nWe are indebted to Kenneth E. Hartmann for critical reading of the manuscript. This study was supported in part by grant from the Ministry of Health, Labour and Welfare of Japan and from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant number 24591686). All authors are free of any conflicts of interest.
\nElectrospinning is the most preferred method because of its low cost compared to nanofiber production methods, production of long and continuous nanofibers, controllable nanofiber diameter, and industrial processing potential. When all these properties are evaluated, it would be appropriate to produce a nanofiber for wound healing by electrospinning. On the other hand, in recent years, interest in polymer materials obtained by the electrospinning method has increased significantly. Materials such as polymers and nanofiber composites can be produced directly by electrospinning. The post-processing of electrospun fibers forms other materials, such as ceramics and carbon nanotubes [1]. Polymer nanofibers obtained by the electrospinning method have a high surface area-volume ratio, flexible in surface functions, have superior mechanical performance, and are versatile in design [2].
Because of all these advantages, the most common and simple method used for tissue framework production is electrospinning. The principle of operation is based on filling the syringe with the polymer solution or melting in the high potential area and spraying it from the tip of the syringe to the collector by applying a voltage to an electrode connected to the tip of the syringe (Figure 1). Here, since the solution sprayed from the syringe is subjected to an electrical field, it elongates at the tip of the needle, and a conical appearance called a Taylor cone is obtained. A typical electrospinning process must be between a high voltage source with positive or negative polarity and a grounded surface so that the fibers can clump together. Spraying the solution in the syringe starts when the potential difference applied from the voltage source reaches the threshold value and equalizes to the electrostatic forces, and is completed by spraying it on the grounded surface. Since the fibers collected on the surface are sprayed with a high amount of pulling, they should be in a fine and regular structure [3, 4, 5].
Schematic representation of the electrospinning process.
The surface tension of the liquid (γ), and the gravitational force (Fg) affect the droplet when the solution, which is the first step of the electrospinning process, comes out of the syringe by forming a droplet. The capillary of internal radius (R), density of the liquid (ρ), and gravitational constant (g) values of the pipe through which the polymer flows are effective in the formation of the radius of the droplet (r0).
When a sufficiently high voltage is applied, the electric force FE, the gravitational force Fg encounter surface forces (Fγ = FE + Fg), and the radius of the droplet decreases from (r0) to r (r < r0) [6].
After droplet formation, the polymer solution overcomes the surface forces under the influence of Coloumb repulsive forces, forming a Taylor cone with an apex angle of 49.3°. Initially straight, the jet segment may become unstable over time and may show twisting and undulating movements as it passes toward the collector. The jet in this region exhibits components of predominantly non-axial electrostatic repulsion forces. Three types of instability can occur as demonstrated by the polymer jet. These instability forms are listed as classical Rayleigh instability, axisymmetric electric field current, and whipping instability. Whipping instability results in a radial torque from the center of the jet, resulting in a high degree of bending instability. The resulting radial jets push each other and separate from the main jet. The interaction between increasing charge density on the one hand and viscous and surface tension forces resisting elongation on the other determines the complexity of the resulting instability [6, 7].
This chapter focused that the electrospinning process, parameters affecting the process such as solution and ambient. After then, it was explained herbal extracts were used to obtain nanofibers by electrospinning method and their application areas. This chapter will provide an overview of the principles of the electrospinning process with various herbal extracts for potential applications in many fields especially biomedical areas.
There are three main parameters of the electrospinning process. These are due to the polymer solution, process, and environmental conditions. In this section, the factors affecting each parameter will be discussed in detail. These parameters and their effects in Table 1 are also shown.
Parameters | Effect of Fiber Morphology |
---|---|
Solution Viscosity ↑ | Fiber Diameter ↑ (within the optimum range) |
Surface Tension↓ | Fiber Diameter ↑ |
Solution Conductivity ↑ | Fiber Diameter ↓(wide diameter distribution) |
Solution Dielectric Constant↑ | Fiber Diameter ↓ |
Voltage ↑ | Fiber Diameter ↓ later ↑ |
Flow Rate ↑ | Fiber Diameter ↑ (if the flow rate is too high, a bead appearance occurs.) |
Temperature↑ | Fiber Diameter ↓ (as the viscosity will decrease) |
Distance Between Tip and Collector↑ | Fiber Diameter ↓ (if the distance between the tip and the collector is too short, a bead appearance occurs) |
Humidity (Moisture) ↑ | Fiber Diameter ↑ (with the optimum range) |
Electrospinning parameters affecting fiber morphology.
To carry out the electrospinning process, the polymer must be in liquid form, in the form of a molten polymer or polymer solution. The physical and chemical properties of the solutions play an active role in the electrospinning process and the resulting fiber morphology. During the electrospinning process, the polymer solution is drawn from the tip of the needle. For this reason, the electrical properties, surface tension, and viscosity of the solution determine the amount of stress in the solution. The evaporation rate also affects the viscosity of the solution as it is stretched. The solubility of the polymer in the solvent determines not only the viscosity of the solution but also the types of polymers that can be mixed with each other [1].
Viscosity is the most important factor determining the flow rate of the solution. In the electrospinning process, the flow rate increases at low viscosity [8]. However, when the viscosity of the solution is too low, fluidity may occur and polymer particles may form instead of fibers. In solutions with lower viscosity, the polymer chain is generally less synthesized with each other [9], less chain entanglement occurs, and thus jet stability is lost. The fibers are collected into the collector as droplets, which first turn into spindle-like structures and then into beaded nanofibers [3]. As the viscosity increases, the formation of the bead structure decreases, and more regular nanofibers are obtained [9]. Therefore, factors that affect the viscosity of the solution also affect the electrospinning process and the resulting fibers.
The molecular weight of the polymer used in the electrospinning process has a direct effect on properties such as viscosity, surface tension, and conductivity, and this interaction determines the nanofiber formation. Molecular weight is explained as the length of the chains of the polymer from which nanofibers will be obtained [4]. The length of the polymer chain will determine the amount of entanglement of the polymer chains in the solvent [1]. Since the viscosity will be higher in polymer solutions with high molecular weight, the formation of beads decreases [10]. Although the increase in molecular weight provides regular fiber formation, if this increase is high, it causes the formation of microstrip structure [11, 12].
When a very small drop of waterfalls into the air, the droplet usually takes on a spherical shape. The liquid surface property that causes this phenomenon, which occurs when the electrical forces are around zero, is known as surface tension [1]. An excessive increase in surface tension adversely affects the electrospinning process. Some surfactants with low concentrations are used to lower the surface tension. The decrease in the surface tension of the solution ensures the formation of finer and smoother fibers and a problem-free electrospinning process [4]. The concentration change in the solutions used directly affects the surface tension [13].
Electrospinning is a method of obtaining nanofibers that repel the charges on the surface by stretching the solution and transfer the electric charge from the electrode to the polymer solution [1, 14]. In the electrospinning system, low electrical conductivity can form beaded fibers as it will create instability and cause the jet to not be able to extend sufficiently, while with high electrical conductivity, the polymer jet can stretch more with the loads it carries and form fibers with a smoother and finer structure [3]. For this reason, it is aimed to increase the electrical conductivity by increasing the concentration. Some additives can also be added to increase conductivity in low-concentration or insufficiently ionic solutions [4]. If the conductivity of the solution increases, the electrospinning jet can carry more charge. For example, the conductivity of the solution can be increased by the addition of ions [1]. By adding salt to an uncharged solution, although electrical neutrality is maintained, salt molecules can dissociate into independently acting positive and negative ions, thereby increasing the electrical conductivity of a solution [15, 16]. These ions can also be obtained by dissolving most drugs or proteins in water. As a result, when a small amount of salt or polyelectrolyte is added to the solution, the increased loads carried by the solution will increase the stretching of the solution and the formation of beaded fibers will be prevented [1].
The insulation constant or dielectric constant is defined as a coefficient that measures the ability of a material to store charge on it [17]. As the dielectric constant of the solutions increases, the charge distribution across the surface of the bubble formed at the needle tip will be more uniform, as there will be more net charge density. Therefore, the ordered structure of the obtained nanofiber is also increasing [3, 4]. It is thought that as the dielectric constant increases, obtaining finer and smoother fibers is due to the application of more tension force to the fluid jet [18].
Another important parameter affecting the electrospinning process is various external factors applied to the electrospinning jet. These factors are voltage, flow rate, temperature, collector effect, nozzle diameter, and the distance between the tip and the collector. Although these parameters are less important than solution parameters, they have a certain effect on fiber morphology.
Voltage is a parameter that induces charges in the solution, overcomes electrostatic forces, and initiates the electrospinning process [1]. As the amount of applied voltage increases, the diameters of the obtained nanofibers will decrease [4]. There are three main reasons for this. The first reason is because of a higher voltage will lead to greater stretching of the solution due to the larger columbic forces in the jet and the stronger electric field. This will reduce the fiber diameter. The second factor is that by using a lower viscosity solution, at a higher voltage, the formation of secondary jets during electrospinning is achieved. Thus, the fiber diameters can become narrower. Another factor that can affect the fiber diameter is the flight time of the electrospinning jet. A longer flight time will allow more time for the fibers to stretch and elongate before being placed on the collecting plate. Therefore, at a lower voltage, the diminished acceleration of the jet and the weaker electric field can increase the flight time of the electrospinning jet, facilitating the formation of finer fibers [1].
In many studies [19, 20, 21], it was observed that the formation of beads on the surface formed with the increase of voltage increased. The increase in bead density due to tension is explained because of increased instability of the jet as it is drawn into the syringe needle in the Taylor cone [1]. Here, bead formation occurs with the excessive acceleration of voltage increase, jet movement, and evaporation [4]. It is also suggested that increasing voltage will increase bead density and at even higher voltage, beads will form fibers of thicker diameter [1].
Despite these studies that the voltage increase creates a bead surface, it has been observed that the production of nanofibers at very low voltage also creates a beaded surface [22]. In this sense, the important thing is to work at a voltage where the flow balance will be stable. With the increase in voltage, the jets coming out of the cone tip reach the collector in an orderly manner, increasing their speed in the electrical field. Here, excessive speed increase or decrease is a factor that will lead to the formation of a beaded surface. In other words, the applied voltage must have an upper and lower limit.
The feeding rate determines the amount of feed in the electrospinning system. A certain feeding rate is needed to maintain the Taylor cone in the system. When the feeding rate increases, there will be an increase in the fiber diameter or the size of the beads formed in the fibers, as there will be more solution volume at the nozzle tip [1]. At low feeding rate, nanofiber production will not be possible because there will not be sufficient feed for the Taylor cone.
As the applied voltage changes, the resulting Taylor cone will also change. At low applied voltages, a hanging drop forms at the tip of the array. The Taylor cone is then formed at the tip of the array. However, as the applied voltage increases (moving from left to right), the volume of the hanging drop decreases until a Taylor cone is formed at the tip of the array. Increasing the applied voltage results in the ejection of the spray through the syringe, which is associated with an increase in bead formation [5].
The temperature parameter consists of three environmental variables: melt temperature, solution temperature, and ambient temperature. As the melt temperature increases, less tension is required due to the decrease in viscosity and fiber diameters decrease [7]. Similar to melt temperature, the temperature of a solution has the effect of both increasing the evaporation rate and reducing the viscosity of the polymer solution. This is because the solution has a lower viscosity and greater solubility of the polymer in the solvent, allowing the solution to be stretched more evenly. With a lower viscosity, Columbic forces can exert a greater tensile force on the solution, thus resulting in smaller diameter fibers [1].
There must be an electric field between the source and the collector (collector) for the electrospinning process to start. Therefore, in most electrospinning systems, the collector plate is made of a conductive material such as aluminum foil, which is electrically grounded such that there is a constant potential difference between the source and the collector. If a non-conductive material is used as a collector, charges from the electrospinning jet will quickly build upon the collector, resulting in less fiber deposition. Fibers collected on non-conductive material generally have a lower packing density than those collected on a conductive surface. This is due to the repulsive forces of the loads that build upon the collector as more fibers accumulate. For a conductive collector, the loads on the fibers are distributed so that more fibers are drawn into the collector. As a result, the fibers can be wrapped closely together [1].
The most commonly used collector types in the electrospinning method are generally flat plates, grids and frames. Apart from these, rotating cylinder, rotating disc, rotating cones, parallel rings, liquid bath and wrapper, pyramid-shaped platform, conveyor belt, two parallel frames, rotor, and thin conductive rod are listed as [7].
The nozzle diameter has a certain effect on the electrospinning process. As the nozzle diameter gets smaller, it provides clogging of the diameter and reduces the amount of beads on the nanofibers. The reduction in occlusion is due to less exposure of the solution to the atmosphere during electrospinning. The decrease in the inner diameter of the hole causes a decrease in the diameter of the nanofibers. As the size of the droplet at the tip of the hole decreases, the surface tension of the droplet increases. It reduces jet acceleration when the same amount of voltage is applied, allowing more time for the solution to stretch and stretch before the collector. The nanofibers formed in this way are finer [1].
The nozzle could be blockage when electrospinning with electrospinning chloroform solutions of PLA. When more than one nozzle is formed, the solvent density may increase, but this will increase the difficulty of solvent removal and nozzle cleaning and compose the deposition of nonwoven fiber in thicknesses >10 mm [23].
The distance between the needle tip and the collector provides the necessary time for the solvent in the polymer jet sprayed from the nozzle tip to evaporate [4]. Changing the distance between the tip and the collector has a direct effect on both the flight time and the electric field strength. As the distance between the tip and the collector decreases, the jet will have a shorter distance to travel before reaching the collector plate. In addition, the electric field strength will increase at the same time, which will increase the acceleration of the jet going to the collector. As a result, there may not be enough time for solvents to evaporate when they hit the collector. When the distance is too low, excess solvent causes the fibers to coalesce where they come into contact [1].
Environmental conditions in the electrospinning process are the factors affecting the electrospinning process. In this sense, humidity, atmospheric type, and pressure cause physical and morphological changes in the formed fibers.
The increase in humidity in the environment adversely affects the electrospinning process. High humidity causes circular pores to form on the nanofiber surfaces obtained. The pore depth increases with increasing humidity. However, the depth, diameter, and number of pores remain constant above a certain humidity [1]. It is not possible to carry out the electrospinning process at very high humidity values [3]. As the humidity level decreases, volatile solvents evaporate quickly, causing drying and making the electrospinning process difficult [9]. For this reason, keeping the humidity level at an optimum level is an important factor.
The type of atmosphere in which the electrospinning process takes place is very important for the smooth running of the process. Different gases have different behavior under the high electrostatic field. For example, helium decomposes under a high electrostatic field and therefore electrospinning is not possible [1]. For another example, with excessively volatile solvents the Taylor cone could dry out. To prevent evaporation in the cone, it is feasible to introduce a local stream of solvent-saturated gas around the cone [23]. The decrease in pressure in the environment adversely affects the electrospinning process [1].
Pressure changes in the electrospinning process make it difficult to ensure the stability of the drafting process. The reduction in pressure surrounding the electrospinning jet adversely affects the electrospinning process. When the ambient pressure drops below atmospheric pressure, the polymer solution in the syringe will have a greater tendency to flow through the needle, resulting in an unstable spray start. As the pressure decreases, rapid solution foaming occurs at the needle tip. At very low pressure, electrospinning is not possible due to the direct discharge of electric charges [1].
Reasons such as health problems, population density, environmental pollution, and increased consumption have encouraged people to seek natural solutions. The use of herbal products in the field of health for their healing properties is increasing day by day. In recent years, plants derived from natural substances such as flavonoids, terpenoids, steroids have received considerable attention due to their different pharmacological properties, including antibacterial, antioxidant, and anticancer activity.
The olive leaf plant, which draws attention with its biocompatible, biodegradable, antioxidant, and antimicrobial properties, has been used by many researchers [24, 25, 26, 27] in the electrospinning process for use in the biomedical field. Similarly, because of its biocompatible, biodegradable and antimicrobial properties, and rosemary plant [28, 29] has been used as a bioactive packaging material and to obtain nanofibers by electrospinning for use in the biomedical field. Many plant extracts such as aloe vera [30, 31], thyme [10], grape seed [32], chamomile [33], green tea [34], grewia mollis [35], gotu kola [36], calendula [37], mangosteen [38], lavender [39] are mixed with different polymers and used in the production of nanofibers for use in the medical field.
The fact that different plants grow in every geography, each plant has different and many effects and the ability to obtain biocompatible, sustainable, organic, and environmentally friendly products have encouraged researchers to work in this field. The use of plants obtained from natural sources as active agents is increasing day by day in areas such as wound healing, tissue engineering, and drug release.
The skin forms the largest part of body weight and is very vulnerable to external forces and effects such as tissue traumas and injuries. Today, wound dressings play a vital role in the healing of such wounds, and wound healing depends on several factors such as selection of wound dressing, physiological state of the wound, and degree of damage. An ideal wound dressing should facilitate wound healing, remove exudates from the wound bed, be non-toxic and allergenic, and act as a barrier against microbes [4, 30]. Conventional wound dressings are generally used to close the wound and absorb the excess discharge. Although in previous studies, it was stated that the dressing should keep the wound dry, it is known that a warm and moist environment on the wound increases the healing of the wound [40]. However, it is a fact that excessive moisture causes wetting and softening of the scar tissues and prolongs the wound healing process [4]. Keeping the humidity level at an optimum level is very important for wound treatment. In addition to the ideal moisture level of modern wound dressings, effective oxygen circulation, air permeability, and low bacterial contamination are the essential qualities sought [40].
Modern wound dressings are composed of water-absorbent granular hydrocolloids, alginate containing mannuronic and guluronic acids, and hydrogel, in which water-absorbing polymers are structured into a three-dimensional network [40]. In recent years, with the rapid development of tissue engineering, nanofiber-based ECM (extracellular matrix) scaffold structures have become widespread [4]. ECM is a collagenous substance commonly found in skin, tendons, cartilage, and bone [11]. Compared to other wound dressings, nanofiber wound dressings have advantages such as hemostasis, high porosity, good fluid absorption capacity, small pore sizes, and large surface area [4]. Hyaluronic acid, collagen, chitosan-based nanofibers are generally used in new generation nanofiber-containing bioactive wound dressings due to their biocompatible, biodegradable, and antibacterial properties [40]. Thus, it ensures the healing of the wound by releasing the active substance in the nanofiber structure onto the wound in a controlled manner.
In recent studies [24, 29, 41, 42, 43], herbal extracts seem to be helpful in fighting infection and accelerating the wound healing process. The use of herbal extracts as wound dressings can nourish the wound site with healing properties such as antimicrobial, anti-inflammatory, analgesic, and tissue regeneration [30]. The long-term toxicity and harmful side effects of herbal extracts are generally insignificant compared to synthetic drugs. The main disadvantage of herbal medicines is that they need to be used in higher dosages than synthetic medicines. Large amounts of herbal medicines extracted from plants reduce their solubility in water or other chemical solvents. Therefore, dissolution of plant extracts almost never occurs in polymer-carriers such as capsules, nanofiber mats, and casting films containing herbal medicines. This may cause adverse effects in applications such as drug release behavior. Despite these problems, herbal drugs promise great success compared to chemical drugs due to their superior performance in wound treatments [10]. The important point here is to extract the herbal extracts in a suitable solvent, to obtain a biocompatible polymer and a nanofibrous structure that preserves its existing effects such as anti-inflammatory and antibacterial and supports the repair of opened wounds.
Tissue engineering is a field that aims to heal damaged or diseased tissues/organs, to maintain, regenerate and develop the functions of normal tissues/organs, and to form tissue scaffolds with repair capability for this purpose. Electrospinning is an application with high potential in many tissue engineering fields such as vasculature, bone, neural, and tendon/ligament. With the electrospinning process, the ability to form aligned scaffolds for anisotropic mechanical and biological properties in the field of vascular grafts, as well as the ability to inhibit smooth muscle cell migration, is provided. In addition, possibilities have been presented to improve vascular grafts with tissue scaffolds that can be obtained by tissue engineering [5, 44].
Nanofibers in tissue engineering must have such as biocompatible, biodegradable (with an acceptable shelf life), tissue-appropriate degradation rate, tissue-appropriate mechanical (strength, stiffness, and modulus) and structural (pore sizes, shape, and structure) properties, and sterilizability [45]. Tissues consist of multiple cell types and works in conjunction with the cell-surrounding extracellular matrix (ECM), which is the tissue scaffold, concealed by regular, micro-sized cells. The ECM is responsible for providing the cells with the needed mechanical support and protecting the cells. The materials used in tissue engineering applications should allow a certain interaction with the cell, the cell’s attachment, proliferation, change, ECM production, and proper progression of this process should be ensured. It should form a supporting function in the formation of new tissues [3, 44].
Approximately, 25% of current prescription drugs are derived from trees, medicinal plants, shrubs, and herbs in nature. The use of herbal extracts with nanofibers produced by electrospinning provides a good potential to form scaffolds for skin regeneration [46]. For example, it has been seen that the nanofibrous structure of the chamomile plant supports collagen fiber accumulation and tissue formation in the dermis [33], and the olive leaf plant has a good potential for tissue scaffolding in biomedical applications thanks to its high antioxidant effect [3]. There are studies on tissue scaffolds containing edible, non-toxic, biocompatible, biodegradable plant extracts with many different contents. It is thought that the applications of plant-based tissue scaffolds will increase in future studies.
Drug delivery systems aim to deliver the drug to the unhealthy region in a controlled and regular manner and to ensure its effectiveness in this region. While drug delivery is generally associated with the delivery of therapeutic agents for the treatment of certain disease states such as cancer, the delivery systems for tissue engineering applications can also apply to the delivery of bioactive agents such as proteins and DNA [5].
In conventional drug delivery systems, successive doses of the drug cause a fluctuating profile of the drug concentration in the blood throughout the treatment period. Therefore, at certain times, concentrations may exceed the recommended maximum (Cmax) concentration with the risk of biotoxicity or fall below the minimum concentration (Cmin), limiting the therapeutic effect. To obtain the highest therapeutic value from the drug, the optimum concentration (C), (Cmin < C < Cmax) in body tissue should be maintained throughout the entire treatment period. Via controlled delivery techniques, the bioavailability of the drug has been designed throughout to be close to this optimum value. In addition, the amount of drug required to be administered is relatively lower in the controlled release mode, minimizing potential side effects [6].
In tissue engineering, the design of the polymer scaffold requires the release of growth factors and other bioactive substances into the growing tissue over a period of time. In nanofiber applications such as wound dressings or artificial leather, the local controlled release of antibiotic substances can aid the healing process. Polymer-based delivery systems can produce controlled drug release by diffusion or chemical bioerosion of the matrix or biodegradation of the linkages connecting the drug to the matrix [6]. These advantages are of great importance in their preference and use.
Polymer-based drug delivery systems; nano or microparticles, hydrogels, micelles, and fibrillar systems. Fibrillated systems form nanofiber-based drug release systems [3]. The release kinetics of the drug is controlled by the morphology of the polymer/drug composite as well as the semi-crystalline structure of the polymer. First, the drug is dissolved at the molecular level in the polymer matrix. The drug is separated as crystalline or amorphous particles in the polymer matrix [6, 47].
The use of herbal-based nanofiber structures in drug delivery systems has increased in recent years. There are different applications such as designing coaxial nanofibers by using olive leaf extract as a bioactive agent [25], producing nanofiber membranes containing aloe vera [48], using nanofibers prepared using the bark of Tecomella undulate (rohida) plant in in-vitro drug release [49]. It is expected that nanofiber drug delivery systems containing herbal extracts will increase therapeutic efficacy, reduce toxicity and ensure compatibility with patients by delivering drugs to the affected area at a controlled rate for a certain period.
Electrospinning is a nanofiber production method that is the most preferred because it is simple, economical, and environmentally friendly, and has many production parameters including solution, process, and environmental conditions. Production of nanofibers by electrospinning process; It is a subject that draws attention with its applications in many fields such as tissue engineering, drug release, filtration, automotive, energy, food industry, cosmetics, agriculture, biosensing. Although polymer contents with synthetic infrastructures are generally preferred in these applications, approaches to using natural agents with few side effects, biocompatible, sustainable, economical, biodegradable, and free from toxic components are increasing [10, 27, 33, 41, 42]. The use of natural components containing active agents in the production of nanofibers is becoming more and more common in the fight against potential health problems that may occur due to the rapidly increasing world population and environmental pollution. Herbal extracts are promising in electrospinning applications with their biodiversity, ability to maintain their biological functionality even after exposure to high electrical voltage, and wound healing effects against pathogenic microorganisms. In addition, it is thought that the use of herbal extracts in different applications in the field of health will become widespread, as they have fewer side effects, and versatile therapeutic properties compared to chemical agents.
The authors declare no conflict of interest.
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Every year, the number of palm oil mills increases rapidly, thus increasing the capacity of fresh fruit bunch waste or effluent discharge. Based on the data from the Malaysian Palm Oil Board in 2012, Malaysia produced 99.85 million tons of fresh fruit bunch (FFB) per year. However, about 5–5.7 tons of water was required in order to sterilize the palm fruit bunches and clarify the extracted oil to produce 1 ton of crude palm oil resulting in 50% of the water turning into palm oil mill effluent (POME). POME is one of the major environmental pollutants in Malaysia. The characteristics of POME and its behavior, if discharged directly, in water are described in this chapter. The suspended solid and nutrient content in POME could be able to support the growth of algae. This chapter aims to demonstrate that POME could be used as a main source for algae production, and this effluent is one of the main environmental problems in the tropical region especially in Malaysia.",book:{id:"6730",slug:"palm-oil",title:"Palm Oil",fullTitle:"Palm Oil"},signatures:"Hesam Kamyab, Shreeshivadasan Chelliapan, Mohd Fadhil Md Din,\nShahabaldin Rezania, Tayebeh Khademi and Ashok Kumar",authors:[{id:"225957",title:"Dr.",name:"Hesam",middleName:null,surname:"Kamyab",slug:"hesam-kamyab",fullName:"Hesam Kamyab"},{id:"237449",title:"Dr.",name:"Shreeshivadasan",middleName:null,surname:"Chelliapan",slug:"shreeshivadasan-chelliapan",fullName:"Shreeshivadasan Chelliapan"},{id:"241504",title:"Dr.",name:"Mohd Fadhil",middleName:null,surname:"Md Din",slug:"mohd-fadhil-md-din",fullName:"Mohd Fadhil Md Din"},{id:"241505",title:"Dr.",name:"Shahabaldin",middleName:null,surname:"Rezania",slug:"shahabaldin-rezania",fullName:"Shahabaldin Rezania"},{id:"241506",title:"Dr.",name:"Tayebeh",middleName:null,surname:"Khademi",slug:"tayebeh-khademi",fullName:"Tayebeh Khademi"},{id:"241508",title:"Dr.",name:"Ashok",middleName:null,surname:"Kumar",slug:"ashok-kumar",fullName:"Ashok Kumar"}]},{id:"38711",doi:"10.5772/51238",title:"Hydrogen Storage for Energy Application",slug:"hydrogen-storage-for-energy-application",totalDownloads:12184,totalCrossrefCites:17,totalDimensionsCites:40,abstract:null,book:{id:"2873",slug:"hydrogen-storage",title:"Hydrogen Storage",fullTitle:"Hydrogen Storage"},signatures:"Rahul Krishna, Elby Titus, Maryam Salimian, Olena Okhay, Sivakumar Rajendran, Ananth Rajkumar, J. 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Many common products and foods are derived from oil palm, its making them one of the most economically important plants. On the other hand, declining supply of raw materials from natural resources has motivated researchers to find alternatives to produce new materials from sustainable resources like oil palm. Oil palm waste is possibly an ideal source for cellulose-based natural fibers and particles. Generally, oil palm waste such as oil palm empty fruit bunches, oil palm trunk, oil palm shell and oil palm ash are good source of biomaterials. Lack of sufficient documentation of existing scientific information about the utilization of oil palm waste raw materials for biomaterial production is the driving force behind the this chapter. Incorporation of various types of biomaterial derived from oil palm waste resources as reinforcement in polymer matrices lead to the development of biocomposites products and this can be used in wide range of potential applications. Properties and characterization of biomaterial from oil palm waste will not only help to promote further study on nanomaterials derived from non-wood materials but also emphasize the importance of commercially exploit oil palm waste for sustainable products.",book:{id:"6730",slug:"palm-oil",title:"Palm Oil",fullTitle:"Palm Oil"},signatures:"Rudi Dungani, Pingkan Aditiawati, Sri Aprilia, Karnita Yuniarti, Tati\nKarliati, Ichsan Suwandhi and Ihak Sumardi",authors:[{id:"220081",title:"Dr.",name:"Pingkan",middleName:null,surname:"Aditiawati",slug:"pingkan-aditiawati",fullName:"Pingkan Aditiawati"},{id:"234728",title:"Dr.",name:"Rudi",middleName:null,surname:"Dungani",slug:"rudi-dungani",fullName:"Rudi Dungani"},{id:"249537",title:"Dr.",name:"Sri",middleName:null,surname:"Aprilia",slug:"sri-aprilia",fullName:"Sri Aprilia"},{id:"249539",title:"Dr.",name:"Karnita",middleName:null,surname:"Yuniarti",slug:"karnita-yuniarti",fullName:"Karnita Yuniarti"},{id:"249541",title:"Dr.",name:"Tati",middleName:null,surname:"Karliati",slug:"tati-karliati",fullName:"Tati Karliati"},{id:"249542",title:"Dr.",name:"Ichsan",middleName:null,surname:"Suwandi",slug:"ichsan-suwandi",fullName:"Ichsan Suwandi"},{id:"249543",title:"Dr.",name:"Ihak",middleName:null,surname:"Sumardi",slug:"ihak-sumardi",fullName:"Ihak Sumardi"},{id:"256251",title:"Dr.",name:"Sri",middleName:null,surname:"Hartati",slug:"sri-hartati",fullName:"Sri Hartati"}]},{id:"52155",doi:"10.5772/64828",title:"EOR Processes, Opportunities and Technological Advancements",slug:"eor-processes-opportunities-and-technological-advancements",totalDownloads:5447,totalCrossrefCites:16,totalDimensionsCites:33,abstract:"Enhanced oil recovery (EOR) processes are well known for their efficiency in incrementing oil production; however, the selection of the most suitable method to adopt for specific field applications is challenging. Hence, this chapter presents an overview of different EOR techniques currently applied in oil fields, the opportunities associated with these techniques, key technological advancements to guide the decision‐making process for optimum applicability and productivity and a brief review of field applications.",book:{id:"5143",slug:"chemical-enhanced-oil-recovery-ceor-a-practical-overview",title:"Chemical Enhanced Oil Recovery (cEOR)",fullTitle:"Chemical Enhanced Oil Recovery (cEOR) - a Practical Overview"},signatures:"Lezorgia Nekabari Nwidee, Stephen Theophilus, Ahmed Barifcani,\nMohammad Sarmadivaleh and Stefan Iglauer",authors:[{id:"37799",title:"Dr.",name:"Stefan",middleName:null,surname:"Iglauer",slug:"stefan-iglauer",fullName:"Stefan Iglauer"},{id:"179076",title:"Dr.",name:"Lezorgia",middleName:"Nekabari",surname:"Nwidee",slug:"lezorgia-nwidee",fullName:"Lezorgia Nwidee"},{id:"179077",title:"Prof.",name:"Ahmed",middleName:null,surname:"Barifcani",slug:"ahmed-barifcani",fullName:"Ahmed Barifcani"},{id:"179078",title:"Prof.",name:"Stephen",middleName:null,surname:"Theophilus",slug:"stephen-theophilus",fullName:"Stephen Theophilus"},{id:"189371",title:"Dr.",name:"Mohammad",middleName:null,surname:"Sarmadivaleh",slug:"mohammad-sarmadivaleh",fullName:"Mohammad Sarmadivaleh"}]}],mostDownloadedChaptersLast30Days:[{id:"52155",title:"EOR Processes, Opportunities and Technological Advancements",slug:"eor-processes-opportunities-and-technological-advancements",totalDownloads:5449,totalCrossrefCites:16,totalDimensionsCites:33,abstract:"Enhanced oil recovery (EOR) processes are well known for their efficiency in incrementing oil production; however, the selection of the most suitable method to adopt for specific field applications is challenging. Hence, this chapter presents an overview of different EOR techniques currently applied in oil fields, the opportunities associated with these techniques, key technological advancements to guide the decision‐making process for optimum applicability and productivity and a brief review of field applications.",book:{id:"5143",slug:"chemical-enhanced-oil-recovery-ceor-a-practical-overview",title:"Chemical Enhanced Oil Recovery (cEOR)",fullTitle:"Chemical Enhanced Oil Recovery (cEOR) - a Practical Overview"},signatures:"Lezorgia Nekabari Nwidee, Stephen Theophilus, Ahmed Barifcani,\nMohammad Sarmadivaleh and Stefan Iglauer",authors:[{id:"37799",title:"Dr.",name:"Stefan",middleName:null,surname:"Iglauer",slug:"stefan-iglauer",fullName:"Stefan Iglauer"},{id:"179076",title:"Dr.",name:"Lezorgia",middleName:"Nekabari",surname:"Nwidee",slug:"lezorgia-nwidee",fullName:"Lezorgia Nwidee"},{id:"179077",title:"Prof.",name:"Ahmed",middleName:null,surname:"Barifcani",slug:"ahmed-barifcani",fullName:"Ahmed Barifcani"},{id:"179078",title:"Prof.",name:"Stephen",middleName:null,surname:"Theophilus",slug:"stephen-theophilus",fullName:"Stephen Theophilus"},{id:"189371",title:"Dr.",name:"Mohammad",middleName:null,surname:"Sarmadivaleh",slug:"mohammad-sarmadivaleh",fullName:"Mohammad Sarmadivaleh"}]},{id:"60752",title:"Biomaterial from Oil Palm Waste: Properties, Characterization and Applications",slug:"biomaterial-from-oil-palm-waste-properties-characterization-and-applications",totalDownloads:2823,totalCrossrefCites:22,totalDimensionsCites:38,abstract:"Oil palm are among the best known and most extensively cultivated plant families, especially Indonesia and Malaysia. Many common products and foods are derived from oil palm, its making them one of the most economically important plants. On the other hand, declining supply of raw materials from natural resources has motivated researchers to find alternatives to produce new materials from sustainable resources like oil palm. Oil palm waste is possibly an ideal source for cellulose-based natural fibers and particles. Generally, oil palm waste such as oil palm empty fruit bunches, oil palm trunk, oil palm shell and oil palm ash are good source of biomaterials. Lack of sufficient documentation of existing scientific information about the utilization of oil palm waste raw materials for biomaterial production is the driving force behind the this chapter. Incorporation of various types of biomaterial derived from oil palm waste resources as reinforcement in polymer matrices lead to the development of biocomposites products and this can be used in wide range of potential applications. Properties and characterization of biomaterial from oil palm waste will not only help to promote further study on nanomaterials derived from non-wood materials but also emphasize the importance of commercially exploit oil palm waste for sustainable products.",book:{id:"6730",slug:"palm-oil",title:"Palm Oil",fullTitle:"Palm Oil"},signatures:"Rudi Dungani, Pingkan Aditiawati, Sri Aprilia, Karnita Yuniarti, Tati\nKarliati, Ichsan Suwandhi and Ihak Sumardi",authors:[{id:"220081",title:"Dr.",name:"Pingkan",middleName:null,surname:"Aditiawati",slug:"pingkan-aditiawati",fullName:"Pingkan Aditiawati"},{id:"234728",title:"Dr.",name:"Rudi",middleName:null,surname:"Dungani",slug:"rudi-dungani",fullName:"Rudi Dungani"},{id:"249537",title:"Dr.",name:"Sri",middleName:null,surname:"Aprilia",slug:"sri-aprilia",fullName:"Sri Aprilia"},{id:"249539",title:"Dr.",name:"Karnita",middleName:null,surname:"Yuniarti",slug:"karnita-yuniarti",fullName:"Karnita Yuniarti"},{id:"249541",title:"Dr.",name:"Tati",middleName:null,surname:"Karliati",slug:"tati-karliati",fullName:"Tati Karliati"},{id:"249542",title:"Dr.",name:"Ichsan",middleName:null,surname:"Suwandi",slug:"ichsan-suwandi",fullName:"Ichsan Suwandi"},{id:"249543",title:"Dr.",name:"Ihak",middleName:null,surname:"Sumardi",slug:"ihak-sumardi",fullName:"Ihak Sumardi"},{id:"256251",title:"Dr.",name:"Sri",middleName:null,surname:"Hartati",slug:"sri-hartati",fullName:"Sri Hartati"}]},{id:"66623",title:"Catalytic Dehydration of Glycerine to Acrolein",slug:"catalytic-dehydration-of-glycerine-to-acrolein",totalDownloads:1418,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"The biodiesel production yields glycerine as a by-product in quantities around 10 vol% of produced biodiesel. Acrolein can be obtained from glycerine by a dehydration reaction. Catalytic processes in gas phase have been developed to obtain acrolein from a renewable feedstock using heterogeneous catalysts. The main process variables are the reaction temperature, the concentration of glycerol in water, and the space velocity in fixed-bed reactors. A thermodynamic study of the equilibrium has been made to estimate the conversion to equilibrium as a function of temperature. The reactors have been heated usually between 523 and 603 K. Generally, an aqueous glycerol solution is preheated in a preheating zone at a temperature enough to vaporize the feedstock, between 473 and 533 K, depending on the concentration of reactant required in the feed. Some of the most active catalysts in the gas-phase reaction (yield >70%) were NH4-La-β zeolite, Pd/LaY zeolite, hierarchical ZSM-5, WO3/ZrO2, WO3/TiO2, ZrOx-NbOx, WOx-NbOx, WO3-SiO2/ZrO2, NbOx-WOx/Al2O3, H3PO4-MCM-41, SAPO-40, NbPSi, Pd-H3PW12O40/Zr-MCM-41, H3PW12O40/Cs-SBA-15, H3PW12O40/Nb2O5, Cs-doped H4SiW12O40/Al2O3, H4SiW12O40/TiO2, and H4SiW12O40/SiO2.",book:{id:"8448",slug:"glycerine-production-and-transformation-an-innovative-platform-for-sustainable-biorefinery-and-energy",title:"Glycerine Production and Transformation",fullTitle:"Glycerine Production and Transformation - An Innovative Platform for Sustainable Biorefinery and Energy"},signatures:"Israel Pala Rosas, Jose Luis Contreras Larios , Beatriz Zeifert and José Salmones Blásquez",authors:[{id:"94936",title:"Dr.",name:"José Luis",middleName:null,surname:"Contreras",slug:"jose-luis-contreras",fullName:"José Luis Contreras"},{id:"284261",title:"Ph.D.",name:"Israel",middleName:null,surname:"Pala-Rosas",slug:"israel-pala-rosas",fullName:"Israel Pala-Rosas"},{id:"284262",title:"Dr.",name:"Jose",middleName:null,surname:"Salmones",slug:"jose-salmones",fullName:"Jose Salmones"},{id:"284263",title:"Dr.",name:"Beatriz",middleName:null,surname:"Zeifert",slug:"beatriz-zeifert",fullName:"Beatriz Zeifert"},{id:"295779",title:"Prof.",name:"Jose Luis",middleName:null,surname:"Contreras",slug:"jose-luis-contreras",fullName:"Jose Luis Contreras"}]},{id:"64816",title:"PVT Properties of Black Crude Oil",slug:"pvt-properties-of-black-crude-oil",totalDownloads:1561,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Precise PVT studies and behavior of phase-equilibrium of petroleum reservoir fluids are essential for describing these fluids and appraising their volumetric behavior at several pressure stages. There are numerous laboratory studies that can be performed on a reservoir sample. The amount of data desired determines the number of tests to be performed in the laboratory. Generally, there are three laboratory tests which characterize hydrocarbon fluids, namely primary study, constant mass depletion, and differential vaporization test. Generally, PVT properties are determined either experimentally or calculated theoretically through published correlations. This chapter presents different PVT laboratory tests that are required to understand the phase behavior of black oils.",book:{id:"7323",slug:"processing-of-heavy-crude-oils-challenges-and-opportunities",title:"Processing of Heavy Crude Oils",fullTitle:"Processing of Heavy Crude Oils - Challenges and Opportunities"},signatures:"Abdelaziz El-Hoshoudy and Saad Desouky",authors:[{id:"201556",title:"Dr.",name:"Abdelaziz",middleName:"Nasr",surname:"El-Hoshoudy",slug:"abdelaziz-el-hoshoudy",fullName:"Abdelaziz El-Hoshoudy"},{id:"210639",title:"Dr.",name:"Saad M.",middleName:null,surname:"Desouky",slug:"saad-m.-desouky",fullName:"Saad M. Desouky"}]},{id:"64885",title:"Environmental Challenges Associated with Processing of Heavy Crude Oils",slug:"environmental-challenges-associated-with-processing-of-heavy-crude-oils",totalDownloads:876,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"The petroleum industry is one of the largest industries in the world and plays a pivotal part in driving a nation’s economy. However, the exploration and exploitation of heavy crude oil have raised series of environmental challenges and caused increased concern for the communities where the oil refineries are cited. Activities such as gas flaring and oil spillage have led to the release of toxic organic and inorganic pollutants, which has resulted in acid rain, climate change, and contamination of soil, water, and air. These environmental hazards have caused adverse effects directly or indirectly to the ecosystem. This chapter offers a general overview of the processes involved in the processing and some of the potential environmental challenges associated with heavy crude oil processing.",book:{id:"7323",slug:"processing-of-heavy-crude-oils-challenges-and-opportunities",title:"Processing of Heavy Crude Oils",fullTitle:"Processing of Heavy Crude Oils - Challenges and Opportunities"},signatures:"Samuel O. Sojinu and Onome Ejeromedoghene",authors:[{id:"265172",title:"Dr.",name:"Samuel",middleName:null,surname:"Sojinu",slug:"samuel-sojinu",fullName:"Samuel Sojinu"},{id:"275861",title:"Mr.",name:"Onome",middleName:null,surname:"Ejeromedoghene",slug:"onome-ejeromedoghene",fullName:"Onome Ejeromedoghene"}]}],onlineFirstChaptersFilter:{topicId:"702",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,annualVolume:11407,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031RJmlQAG/Profile_Picture_1600760167494",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung in Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture in college. Dr. Chen's research interests are bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published over 60 research papers, reviewed over 260 manuscripts, and edited at least 150 papers in international peer-review journals.",institutionString:null,institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:25,paginationItems:[{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81271",title:"The Diversity of Parvovirus Telomeres",doi:"10.5772/intechopen.102684",signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:22,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"80187",title:"Potential Utilization of Insect Meal as Livestock Feed",doi:"10.5772/intechopen.101766",signatures:"Sipho Moyo and Busani Moyo",slug:"potential-utilization-of-insect-meal-as-livestock-feed",totalDownloads:101,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Animal Feed Science and Nutrition - Production, Health and Environment",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",subseries:{id:"20",title:"Animal Nutrition"}}},{id:"79909",title:"Cryopreservation Methods and Frontiers in the Art of Freezing Life in Animal Models",doi:"10.5772/intechopen.101750",signatures:"Feda S. Aljaser",slug:"cryopreservation-methods-and-frontiers-in-the-art-of-freezing-life-in-animal-models",totalDownloads:160,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Animal Reproduction",coverURL:"https://cdn.intechopen.com/books/images_new/10664.jpg",subseries:{id:"28",title:"Animal Reproductive Biology and Technology"}}}]},overviewPagePublishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"7233",title:"New Insights into Theriogenology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",slug:"new-insights-into-theriogenology",publishedDate:"December 5th 2018",editedByType:"Edited by",bookSignature:"Rita Payan-Carreira",hash:"74f4147e3fb214dd050e5edd3aaf53bc",volumeInSeries:1,fullTitle:"New Insights into Theriogenology",editors:[{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}}]},{type:"book",id:"7144",title:"Veterinary Anatomy and Physiology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7144.jpg",slug:"veterinary-anatomy-and-physiology",publishedDate:"March 13th 2019",editedByType:"Edited by",bookSignature:"Catrin Sian Rutland and Valentina Kubale",hash:"75cdacb570e0e6d15a5f6e69640d87c9",volumeInSeries:2,fullTitle:"Veterinary Anatomy and Physiology",editors:[{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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