Importance of radiology imaging techniques in the diagnosis of brain tumours.
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The development of radiological imaging techniques for the evaluation of brain tumours has progressed significantly in recent years. Two modalities that play a crucial role in the evaluation of brain tumours in preoperative time to detach are computed tomography (CT) and magnetic resonance imaging (MRI).
Despite the new digital radiological techniques, which are used widely in clinical practice, imaging methods such as CT and MRI eliminate x-ray from the examination algorithm of brain tumours. An x-ray of the skull may detect changes that can lead to suspicion of a tumour in the intracranial space and subsequent examination using CT or MRI.
It is important to distinguish tumoural from non-tumoural lesions, and to determine their spatial location. New, advanced imaging CT and MRI techniques provide more detailed characteristics of brain tumours, and thus, more choices of appropriate therapeutic management of the patient. These techniques also play a significant role in monitoring the effect of the therapy.
Diagnosis of tumours has improved considerably due to the introduction of new imaging CT and MRI techniques. These techniques, and the contrast medium in particular, provide anatomical and structural information about brain tumours, and information about the physiology, metabolism, and haemodynamics of individual tumours. The importance of radiology imaging techniques, and their role, in the diagnosis of brain tumours are listed in Tables 1 and 2.
\n\t\t\t\t | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
CT | \n\t\t\tscreening method | \n\t\t
MRI | \n\t\t\tmethod of choice | \n\t\t
DSA | \n\t\t\tmostly used for determination of blood supply and embolization of hypervascular tumours | \n\t\t
US | \n\t\t\tintraoperative navigation | \n\t\t
X – ray | \n\t\t\tlimited | \n\t\t
Conventional invasive X – ray methods | \n\t\t\tobsolete | \n\t\t
Importance of radiology imaging techniques in the diagnosis of brain tumours.
\n\t\t\t\t | \n\t\t||
\n\t\t\t\t | \n\t\t\tDetection | \n\t\t|
Characterization | \n\t\t\tlocalization | \n\t\t|
size | \n\t\t||
margins | \n\t\t||
extension | \n\t\t||
midline shift | \n\t\t||
compression | \n\t\t||
contrast enhancement | \n\t\t||
vascularity | \n\t\t||
supplying vessels | \n\t\t||
perifocal oedema | \n\t\t||
Differentiation | \n\t\t\tbenign vs malignant | \n\t\t|
Staging | \n\t\t||
tumour embolization | \n\t\t||
surgical planing | \n\t\t||
\n\t\t\t\t | \n\t\t\tsurgical navigation | \n\t\t|
\n\t\t\t\t | \n\t\t\tmonitoring the effect of treatment | \n\t\t|
exclude recurrence | \n\t\t||
distinguishing recurrent tumour from radiation necrosis | \n\t\t
Role of radiology imaging techniques in brain tumours
For decades, diagnostic imaging dominated conventional non-invasive and invasive methods, and later invasive contrast x-ray techniques. During the second half of the twentieth century, a number of different projection x-ray radiographs of the head and their modifications, as well as complex invasive contrast imaging techniques, such as pneumoencephalography, ventriculography, and myelography, were improved [1]. Another imaging method is ultrasonography, which can be used for neuronavigation during operation of brain tumours.
In the past, conventional non-invasive x-ray examination (radiography of the head) was the basic diagnostic method in neuroradiology. The baseline projections are posteroanterior (PA) and lateral x-ray projections of the skull. A PA projection is centred by orbitomeatal lines and provides anatomical information about the skull and frontal structures. A lateral projection shows the configuration of the skull and the skull base.
Modification of a PA projection by Caldwell with an x-ray beam inclination of 15°–23°, caudal to the orbitomeatal line, provides a clearer view of the
Sella turcica (lateral projection): destruction by tumour
A submentovertical projection is an axial projection of the skull with the x-ray beam passing approximately perpendicular to the orbitomeatal line, and is suitable for imaging the
Pneumoencephalography is an imaging method in which the lumbar or suboccipital approach is used to instill air into the cerebral ventricles and the subarachnoid spaces after removing approximately 10–30 mL of cerebrospinal fluid [2].
Ventriculography is an imaging method in which, through a trepanation hole, air is introduced into each lateral brain ventricle after the collection of cerebrospinal fluid [3].
These imaging x-ray methods are currently not used in clinical practice.
Before the era of CT and MRI, panangiography was the essential imaging technique of neuroradiology in the diagnosis of brain tumours. A brain tumour manifests itself in angiographic images by indirect signs, such as dislocation of intracranial arteries, depending on tumour size and location; tumoural vessels filling with the contrast medium, tumour vascularization; or vascular occlusion and stenosis [2].
With the onset of CT and MRI, the position of angiography has gradually changed. Currently, due to a new generation of digital radiological technology and rapid development of intracranial catheterization techniques and instrumentation, digital subtraction angiography is a highly specialized imaging method in interventional radiology, with many therapeutic implications.
Ultrasound is a widely available, non-invasive diagnostic method without negative biological effects. Principally, it is applied, in the primary examination of the brain in prenatal and postnatal diagnoses, and in the examination of cerebral arteries. Currently, ultrasonography, used in planning operational strategy and choice of neurosurgery access, has been replaced by new, and more accurate, neuronavigation systems using MRI data. Ultrasound with a high-frequency transducer can be used to monitor changes during brain tumour operations in real time [1] (Figure 2.).
Intraoperative ultrasound navigation with colour flow mapping, showing peripheral vascularization of a brain tumour with solid and cystic parts
From its first test scan on a mouse, in 1967, to current medical practice, the CT scanner has become a core imaging tool. Initially financed by money from Beatles\' record sales, the first patient scan was performed in 1971. Only 8 years later, a Nobel Prize in Physics and Medicine was awarded to Gofrey Newbold Hounsfield and Allan McLeod Cormack for their discovery [4]. The prototype (EMI Ltd.) was installed at Atkinson Morley’s Hospital in South London where the first patient, a middle aged lady with a suspected frontal lobe tumour, was scanned on 1st October 1971 [5].
The rapid development of CT scanners, a new generation of CT devices, and advanced postprocessing technologies in recent years has enabled the creation of progressive, advanced CT protocols for the diagnosis of individual anatomical regions with respect to the pathological processes that can be diagnosed. Technological improvements and new CT applications in neuroradiology are mainly related to CT angiography and CT perfusion with a dynamic contrast agent bolus [1].
The basic CT examination of brain tumours involves standard non-contrast enhanced and contrast enhanced imaging (Figure 3.). Compared to MR, CT is superior in the detection of calcification and bone abnormalities, and it is also less time consuming.
In CT diagnosis, depending on the type of examination, iodinated contrast agents are administered, in different quantities and by different modes. Iodinated contrast agents are divided into ionic, high-osmolar contrast agents and non-ionic, low-osmolar or iso-osmolar contrast agents. Intravenous administration of contrast agents may cause various negative allergic reactions, which are divided into early (within 20 min) and late effects. In practice, non-ionic contrast media are generally preferred as, due to their low osmolarity, they result in significantly fewer negative effects [6].
Contrast enhanced CT of brain tumour: irregular peripheral enhancement of glioblastoma (the image displayed is of the same patient as displayed in
Examination of blood vessels using CT angiography is a non-invasive imaging method which is conducted in various ways: imaging individual sections, maximum-intensity projection (MIP), shaded surface display (SSD), the volume-rendering technique (VRT), multi-planar reconstruction (MPR), and virtual angiography. Improvement in the quality of CT angiography, and the new generation of CT equipment gives rise to the possibility of longer scans, faster scan times with display of the arterial phase of contrast filling with the lowest venous infiltration, and better resolution with improved vascular details.
CT perfusion (Figure 4.) in the diagnosis of brain tumours allows assessment of tumours on the microvascular level through a dynamic scanning sequence during an intravenous bolus injection of a contrast agent. This is a relatively new technique that is used in neuroimaging for quantitative and qualitative assessment of cerebral perfusion by the parameters of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP). Maps with colour-coded flow rates can be obtained by using postprocessing software. Due to this technique, it is possible to assess the state of vascularization and haemodynamics of brain tumours and their differentiation [7 - 9].
Historically, many scientists have contributed to the study of NMR (MRI), which led to construction of reliable MR scanners for clinical practice. Isidor Isaac Rabi in 1930 began by studying the magnetic properties of atomic nuclei (Nobel Prize in Physics in 1944) [10]. The first successful nuclear magnetic resonance experiment with NMR precision measurements was made independently in 1946 by Felix Bloch and Edward Mills Purcell (they jointly received the Nobel Prize in Physics in 1952). In 1971, Raymond Vahan Damadian, measured T1 and T2 relaxation times of excised normal and cancerous rat tissue and stated that tumour tissue had longer relaxation times than normal tissue. He is the inventor of the first MR Scanning Machine (1977) [11]. In March 1973 Paul C. Lauterbur published the first 2D NMR images of two 1 mm capillaries filled with water [10] and in 1974 the image of thoracic cavity of mouse. He called his imaging method zeugmatography. This term was later replaced by NMR imaging [12]. Peter Mansfield with Grannel described the use of magnetic field gradients to acquire spatial information in NMR. P.C. Lauterbur and Sir Peter Mansfield received the Nobel Prize in 1952. The first commercial MR scanner (Picker Ltd.) in Europe was installed in 1983 in Manchester Medical School.
CT perfusion of a brain tumour across the solid part of the tumour (the image displayed is of the same patient as displayed in
The main advantages of MRI are the possibilities of imaging individual anatomical regions in vivo with high tissue contrast, imaging in arbitrary planes, non-invasivity, and the absence of demonstrable detrimental effects on human health. Qualitative evaluation of tissues allows for four basic physical attributes: T1 and T2 relaxation, proton density, motion, and flow.
Conventional MRI techniques provide information about the anatomical conditions of brain tissue, the tumour itself, and its relationship with its surroundings. In contrast to CT, conventional MRI techniques are significantly more sensitive, but as they are nonspecific, they often provide limited information about tumour physiology.
The conventional MRI protocol in the diagnosis of brain tumours includes standard T1-weighted imaging (spin echo [SE], turbo spin echo [TSE], gradient echo, three-dimensional [3D] sequences, and dynamic studies), T2-weighted imaging (SE, fast spin echo [FSE] or TSE, and 3D sequences), “dark fluid” T2-weighted imaging (proton density [PD] and fluid-attenuated inversion recovery [FLAIR]), gradient echo (GRE T2, T2 * GRE, and GRE 3D T1), inversion recovery (IR) (FLAIR, T1 IR, and short-time inversion recovery [STIR]), and fat suppression (FS) (STIR and T1 FS) [13] (Figure 5.).
Sagittal non-contrast enhanced T1W image: hyperintense signal of pericallosal lipoma.
Brain tumours show variable pathomorphological manifestations in MRI, which depend on the structure of different types of tumours. They may have a homogeneous or an inhomogeneous structure, and depending on whether they are focal lesions or infiltrative and growing, they are sharply contoured or diffuse [14].
In general, brain tumours in T1-weighted imaging are hypo- or isointense and in T2-weighted imaging are hyper- or isointense. The tumour’s signal is modified by the intralesional proportion of individual components. Tumours may contain solid, cystic, necrotic, or haemorrhagic components, fatty tissue, or an increased proportion of protein in intracystic components. Not all tumours cause oedema of the brain tissue, which may have a different range [13, 15].
In some cases, visualization of brain tumours in non-contrast imaging can be difficult; therefore administration of a paramagnetic contrast agent is necessary. Contrast enhancement of brain tumours is variable and dependent on tumour neovascularization.
MRI shows intracranial arteries, veins, and venous sinuses at high-quality. Magnetic resonance angiography (MRA) can be implemented using several techniques: phase-contrast MRA (PC MRA), time-of-flight MRA (TOF MRA), and contrast-enhanced MRA (CE MRA) [16].
Tumour angiogenesis can be dynamically monitored in vivo by 3D-CTA and 4D-CE-MRA. Of the two methods, 3D-CTA has better spatial resolution, but 4D-CE-MRA allows temporal resolution of tumour angiogenesis [17].
MRA allows detailed evaluation of intracranial vascular structures, not only because of purely pathological changes of vascular origin, but also in relation to brain tumours.
In addition to non-contrast enhanced imaging, magnetic resonance examination is realized with contrast agents, which improves visualization and demarcation of the tumour. Contrast agents used in MRI are paramagnetic substances containing gadolinium chelates; they cause shortening of the T1 and T2 relaxation times, resulting in a stronger T1 and a lower T2 signal, and they also increase the contrast between two tissues with different quantities of the contrast agent. Increase of T1 signal is more significant, compared with the degree of weakness of the T2 signal; therefore T1-weighted sequences are used after contrast administration (Figures 6-8.).
Axial contrast enhanced T1W image: homogeneous enhancement of multiple meningiomas right supratentorial in patient with neurofibromatosis type 2.
Contrast agents for MRI can be divided into several categories: intravenous contrast agents, which include the majority of non-specific and specific contrast agents; oral contrast agents for display purposes of the gastrointestinal tract; and interstitial contrast agents. According to the space distribution of contrast agents, they are classified into extracellular organ-nonspecific and intracellular organ-specific contrast agents. In the diagnosis of brain tumours intravenous extracellular organ-non-specific contrast agents are used, which have the ability to pass through the blood–brain barrier [18].
Different types of contrast enhancement and common types of brain tumour are listed in Table 3.
First patient examination. Axial contrast enhanced T1W image displays almost no contrast enhancement in the right frontal
Second patient examination. Axial contrast enhanced T1W image displays irregular peripheral enhancement of right frontal tumour (the image displayed is of the same patient as displayed in
\n\t\t\t\t | \n\t\t|
no enhancement | \n\t\t\tLow grade astrocytoma | \n\t\t
diffuse homogeneous | \n\t\t\tMeningioma | \n\t\t
diffuse inhomogeneous | \n\t\t\tPleomorphic xanthoastrocytoma | \n\t\t
ring enhancement | \n\t\t\tMetastasis | \n\t\t
irregular peripheral enhancement | \n\t\t\tGlioblastoma | \n\t\t
mural nodule enhancement | \n\t\t\tHaemangioblastoma | \n\t\t
Different types of contrast enhancement of brain tumours and common types of brain tumour.
Early and accurate diagnosis is the first precondition of the successful treatment of brain tumours. The basic method of determining species diagnosis and grading is the histopathological examination. Biopsy is an invasive method with the risk of possible complications. At the time of the development and practical use of modern, advanced diagnostic techniques, the role of radiodiagnostic imaging modalities was not limited to the assessment of pathological-anatomical conditions [9].
Advanced magnetic resonance techniques in neuroradiology evaluate changes at the microvascular, haemodynamic, and cellular levels of brain tumours, and in addition to structural changes, evaluate changes at the metabolic and biochemical levels [19].
Incorporation of new diagnostic techniques, such as diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), tractography, perfusion-weighted imaging (PWI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI), into the diagnostic protocol allows us to obtain detailed information about tumour lesions. This presents the best possibility of accurate grading of brain tumours in the preoperative time, allowing us to select the most appropriate therapeutic management for the patients [20].
New techniques lead to better quality monitoring of the effects of therapy.
The theory of diffusion is based on constant, disordered, random motion of water molecules in all directions (Brownian motion). Biological tissues in which diffusion is the same in all directions is isotropic; if diffusion is restricted in one direction, tissues are anisotropic. The most common barrier to diffusion is the cell wall. Cerebrospinal fluid is the isotropic field; diffusion in gray matter in all directions compared to the liquor is limited but also isotropic. White matter is the anisotropic region because here diffusion progresses with greater intensity in the direction within axons [21].
DWI is echo-planar imaging that measures the random motion of water molecules (i.e. diffusion in biological tissue). The diffusion capacity of water protons is tissue-specific and creates a specific contrast on DWI. On diffusion sequences, the motion of water protons in biological tissue causes changes in the signal. These signal changes are quantified by calculating the apparent diffusion coefficient map (ADC) [22] (Figure 9.).
DWI, which is currently a routine part of imaging protocols, plays an important role in the assessment of the cellularity of biological tissue. In the diagnosis of brain tumours, DWI is applicable in differential diagnosis of cystic lesions, abscesses, necrosis, and metastases. In addition, DWI has a fundamental role in the evaluation of the age of brain ischemia, in imaging of traumatic changes, and in evaluation activities of demyelinating lesions [23].
Possibilities of using the ADC in differential diagnosis of intracranial tumours, and differentiating peritumoural oedema and infiltration, have been studied since the beginning of the 21st century. Most studies have concluded that the ADC is useful for distinguishing peritumoural infiltration only and cannot provide information on the degree of differentiation of glial tumours. However, they found that in tumour tissue with high cellularity, ADC values were reduced compared to tumours with low cellularity; thus the probability of higher grading is reduced for solid tumours with high values of the ADC. For tumours with a cystic component, such as glioblastoma multiforme, the relationship between the ADC and the grading is below the level of statistical significance [24].
Axial ADC map showing the right frontal hyperintensity of a tumour (the image displayed is of the same patient as displayed in
DTI is an advanced magnetic resonance technique that allows visualization of white matter tracts, and describes the movement of water molecules by using two parameters, mean diffusivity (MD) and fractional anisotropy (FA), which represent the directionality of water diffusion [25].
The postprocessing of DTI data using software generates maps of FA and ADC using DWI images. Reduction of FA surrounding white matter of the tumour indicates the suspicion of peritumoural white matter infiltration by tumoural elements [26]. Using 3D software applications, 3D image tracts are created, allowing imaging of the spatial configuration of white matter structures, such as the corticospinal tract, and configuration of the
Thus, DTI provides other important information that can help distinguish infiltrative growing tumours from bounded tumours and, together with assessment of the ADC and conventional MRI with a contrast agent, the grading of tumours can be better specified [28 - 30].
DTI: destruction and deviation of white matter tracts by anaplastic astrocytoma.
The rapid growth of cells is a result of the increased metabolic demands of a tumour. Cellular hypoglycaemia and hypoxia result in the production of cytokines of angiogenesis (vasoactive endothelial growth factor) followed by tumour neovascularization, which leads to a higher volume of blood flow through tumour tissue. Tumour neovascularization and haemodynamic changes are the basic principles of perfusion MRI, which evaluate the blood supply to brain tissue by four parameters: CBV (the quantity of blood in a given volume in mL/100mg), CBF (the blood flow in brain tissue in mL/100g/min), MTT (the average time for arteriovenous passage of blood in a given volume in seconds), and TTP (the average time to maximum density in the scanning area in seconds) [31, 32].
PWI uses fast, dynamic, epiplanar imaging sequences with a bolus of a paramagnetic contrast agent, 0.2 mmol/kg body weight, at an injection rate of 5 mL/s, approximately 5-10 seconds after the start of imaging sequences, followed by an injection of 20-30 mL of saline. The passage of the contrast agent through vascularized parts of the tumour leads to a reduction in signal intensity. Converting the values of individual parameters by postprocessing to the colour range creates maps with different blood flows. Regional cerebral, and tumour, vascularity is correlated with the CBV.
With PWI it is possible to determine tumour grading non-invasively. In general, high-grade tumours have higher CBV values than low-grade tumours. PWI is also used for localization of the parts of a tumour with a high degree of vascularity for the purpose of stereotactic biopsy. PWI helps to define the edge of a tumour, which is important in planning surgical treatment radiotherapy. PWI is also used to monitor the effect of treatment on patients. In the field of radiation changes, using conventional magnetic resonance techniques, it is difficult to differentiate the eventual recurrence of a tumour. Postirradiation changes have lower CBV values, and through PWI, it is possible to detect areas with increased perfusion, which correspond to tumour recurrence. Increasing specificity in these cases allows the combination of PWI with MRS [33].
Based on recent achievements in the field of MRS, the diagnostic proportion of proton MRS has significantly increased, in the past decade progressing from basic and clinical research to routine clinical practice. MRS is a non-invasive method and currently is part of the advanced diagnostic protocol in neuroradiology. MRS can determine pathological changes in brain tissue long before conventional techniques [34].
MRS provides biochemical and metabolic information about brain tumours and their surrounding tissues. Thus MRS, contributes significantly to the distinguishing of tumour from non-tumour lesions, the type of diagnosis and tumour grading in preoperative time, oedema from infiltrative growing tumours, the monitoring of tumour response to treatment and distinguishing postirradiation necrosis from tumour recurrence [35].
MRS by non-invasive and non-destructive methods detects, in vivo in brain tissue, diagnostically important compounds such as those containing choline (Cho – a key marker of cell membrane stability), creatine (Cr – an indicator of the energy status, often used as a reference value),
Changes in biochemical processes at the cellular level precede macroscopic changes; therefore, MRS is able to detect the development of pathological processes in brain tissue before conventional MRI techniques. MRS and MRI use magnetic characteristics of the atomic nucleus; in obtaining the signal, they work on the same physical principle, but the data processing and interpretation for each are different. MRI provides detailed information about the pathological-anatomical state of brain tissue [37].
Whereas, MRS detects metabolic signals and results in a spectrum in which the position of the signal of a specific metabolite is expressed on the horizontal axis in chemical shifts specified in parts per million (ppm), and the vertical axis reflects the intensity of the signal. The chemical shift and shape of the signal is characteristic for each metabolite [38] (Figure 11.).
MRS: a typical sample 1H MR spectrum in the lesion. Cre2, Cho, Cre, NAA, lac (the image displayed is of the same patient as displayed in
In practice, there are two basic techniques of MRS, single voxel spectroscopy (SVS) and chemical shift imaging (CSI). The result of SVS is one spectrum, which shows the overall distribution of individual metabolites in a limited volume of tissue (voxel) in a volume of 2-8 mL. CSI measures the concentration of metabolites in a selected volume of brain tissue divided into many small voxels. The result is an individual spectrum for each voxel, and the imaging of the distribution of the concentration of individual metabolites in the examined area is produced as a spectroscopic map (Figure 12.).
In clinical practice, MRS is realized through the anatomical imaging of brain tissue using conventional MRI. The spectra are displayed together with conventional MRI images, which characterize the anatomical location of the measured area selected for spectroscopy [38].
The results of the spectra are evaluated by the relative intensity of the signals and the ratios of observed metabolites are typically set to creatine or choline (for example, NAA/Cr, NAA/Cho, or NAA/Cr + Cho). Different types of tumours are manifested by a characteristic spectroscopic profile. Primary tumours are characterized by reducing the concentrations of NAA and
MRS: Coloured metabolic map of the metabolic ratio of total cholines to the signal of the total NAA signal (not resolved to its components), tCho:tNAA (the imaged displayed is of the same patient as displayed in
Functional magnetic resonance imaging (fMRI) is an MRI procedure that indirectly measures the brain activity by means of deoxyhaemoglobin concentration or blood perfusion changes.
The 1st technique, known as BOLD (blood oxygenation level dependent), is the most popular and frequently used [39]; a relative decrease in deoxyhaemoglobin concentration in the active brain tissue, due to an excessive increase of regional blood flow, and corresponding increase of oxyhaemoglobin. Oxyhaemoglobin is, however, less effectively deoxygenated by active brain tissue compared to inactive brain tissue in physiological conditions. Relative changes of diamagnetic oxyhaemoglobin and paramagnetic deoxyhaemoglobin can be easily measured by fast T2-weighted echo-planar (EPI) acquisitions. Their temporal resolution, approximately 100 ms per image slice, is good enough to compare several brain images in rest and active (performing sensory, motor or cognitive task) conditions. The statistical maps that result from this, coregistered with structural MRI (Figure 13.), can provide precise information (in the order of millimetres) about the position and the size of brain regions involved in the processing of each respective task, and, sometimes the dynamics of such processing.
The 2nd group of techniques can evaluate the changes of blood flow in brain tissue using special exogenous diffusible tracers like fluorinated halocarbons, deuterated water, 17O -water and 13C-hydrocarbons, or magnetically labelled endogenous blood water (arterial spin labelled perfusion, ASL). The latter technique is non-invasive and very promising for future clinical applications. It can substitute some nuclear medicine diagnostic methods while providing images with better spatial and temporal resolution. Compared to BOLD techniques, ASL can provide not only relative differential maps, but it also provides quantifiable information about absolute blood flow values (in ml/g/min) in selected brain regions [40]. Thus, it can show the regions activated by some tasks, and also pathological tissue with increased or decreased perfusion compared to normal brain tissue [41]. However, the intrinsic signal-to-noise ratio of ASL is lower compared to BOLD measurements, and currently the majority of scanners are not equipped with the respective product sequences to perform routine clinical ASL procedures.
fMRI: activation of motor cortex during physical stimulation.
Presently, in tumour imaging, fMRI is used predominantly for the preoperative localization of eloquent cortical regions that may have been displaced, distorted or compressed by the tumour [42]. FMRI can provide an alternative to invasive mapping techniques (IMTs), with many benefits, particularly in those patients that are unable to undergo awake craniotomy or other stereotactic diagnostic procedures. FMRI data can be very helpful in neuronavigation, especially if the eloquent region is hidden in the depth of sulci and/or cannot be stimulated during the surgery [43].
The sensitivity of fMRI recordings can be increased by the use of stronger magnetic fields. A shorter scanning procedure, higher signal-to-noise-ratio, and increased spatial resolution of the resultant images favour the usage of 3T and are stronger compared to conventional 1,5T scanners [44].
However, the limitations of fMRI are not a result of poor engineering or the low power of the scanners; the main pitfalls are due to complicated functional brain organization and inappropriate diagnostic protocols that ignore this organization [45]. There are always several brain regions involved in the processing of every sensory/motor/cognitive task. It is upon the examiner to choose the best one, to adjust the statistical thresholds of the fMRI map (which determines the number and the size of activated brain regions), and to recognize which regions are eloquent.
A coregistration of the data provided by several different functional and/or structural MRI techniques (e.g. BOLD, ASL, diffusion tensor imaging, MR spectroscopy, 23Na-MRI) is suitable for future improvements of functional MRI diagnostics.
Introduction of CT, MRI, and microsurgical operating techniques into clinical practice have resulted in progress in the neurosurgical therapy of brain tumours. The application of new MRI techniques and microsurgery allows for the resection of tumours in functionally important brain regions.
Neuronavigation is a common method of preoperative localization of brain tumours. It uses imaging materials of preoperative MRI examinations, 3D sequences and DTI and fMRI data, that are transferred to a computer database of a neuronavigation device; which, after data processing and registering of the patient\'s head position, allows for planning of an optimal trajectory for operating on the brain tumour [46].
According to the virtual reality planning, neurosurgeons could obtain more anatomic information and choose the best approach for tumour resection, which would result in a better prognosis for patients [47].
The disadvantage of current navigation systems is that it is impossible to update data during the neurosurgical procedure. A shift in brain structures and tracts of white matter as a result of the evacuation of cerebrospinal fluid, tumour resection, or gravity makes navigation inaccurate. These disadvantages deal intraoperative using of imaging methods – intraoperative ultrasonography and MRI [48].
Intraoperative MRI displays actual dynamic changes in deformable brain tissue during surgery, and helps in early detection of potential tumour residue. Data transfer from intraoperative MRI to the neuronavigation system is possible, and data for neuronavigation can be updated repeatedly. For this purpose, different types of magnetic resonance devices are used. The presence of a magnetic field requires the use of compatible surgical instruments.
Intraoperative ultrasonography with new devices and high resolution is a cheaper alternative to MRI, with the advantage of imaging in real time; it provides actual images of the tumour, surrounding structures, and major blood vessels during surgery [1].
Digital subtraction angiography (DSA) is a computer-assisted x-ray technique that subtracts images of bone and soft tissue to permit viewing of the cardiovascular system [49].
At the beginning of the process of subtraction, an image (the mask) is obtained before arrival of contrast material at the area of interest, and the mask image is placed into one of two digital memories. Then, one or more subsequent images are obtained after the arrival of a contrast bolus and placed into a second digital memory. The mask image is digitally subtracted from the succeeding contrast image, resulting in contrast-filled structures that are rendered visible free of background detail. Subtraction is performed in real time [50].
Iodine contrast media are used for the visualization of vessels, however cerebral angiography using gadolinium as an alternative contrast medium in a patient with severe allergy to iodinated contrast medium may be performed [51].
Radiation, today known as X-rays, was discovered by the German physicist Wilhelm Röntgen (March 27, 1845–February 10, 1923) on November 8, 1895 [52]. Discovery of X-rays is ranked as one of the best discoveries in medicine. X-rays are electromagnetic waves. The range of wavelengths corresponding to diagnostic imaging span from about 0.1 nm (at 12.4 keV) to 0.01 nm (at 124 keV) [53]. This type of radiation is ionizing.
In a vacuum X-ray tube, the electrons that make up the beam are emitted by a heated cathode filament. The electrons are then focused and accelerated towards the focal spot by a high voltage that is applied between the cathode filament and the anode. A generator is used to supply the X-ray tube with a controlled high voltage between the cathode and anode, and a controlled current to the cathode. The electron beam strikes the rotating anode “target” and part of its kinetic energy (less than 1%) is converted into X-ray photons, while the rest is converted into heat, which heats up the anode. The X-ray beam leaves the tube through the tube window and passes onto the patient. Some of the X-rays pass through the patient, while some are absorbed. The resulting radiation pattern is detected by a flat panel digital X-ray detector (FPD).
FPD system is superior to the image intensifier as it visualizes small intracranial vessels combined with a significant reduction of radiation dose, and is able to create high-quality 3D DSA images on which high spatial resolution allows precise visualization of small vessels, such as perforating vessels [54]. DSA images are then displayed on the LCD monitor with high resolution and different screen layouts, which can be connected to several image sources.
The first carotid angiography was performed by Portuguese Egas Moniz (1874-1955) in 1927; he is considered as a pioneer of cerebral angiography. He reported the first case of cerebral angiography at the Societe de Neurologie in Paris on July 7, 1927 [55]. Surprisingly, most angiograms were performed to visualize the intracranial portion of the carotids in cases of tumours, to look for abnormal displacement of arterial branches, with little interest in the vascular disease itself [56].
The technique, how to obtain safe access to blood vessels was published by Sven-Ivar Seldinger (1921-1998) in 1953 [57]. DSA is an invasive technique, performed using a catheter; the most commonly used approach is the transfemoral approach. At the end of angiography, the puncture site can be safely closed by a closure device [58].
DSA is used to detect the blood vessels supplying the brain tumours, and also to control the hypervascular tumour embolization (meningiomas, paragangliomas, haemangiopericytomas, juvenile nasopharyngeal angiofibromas and intraaxially located tumours: haemangioblastomas (Figure 14.), hypervascularized metastases and ependymomas). Presurgical or palliative embolization of a tumour can be performed by either an intraarterial catheterization approach or direct puncture of the tumour artery [59].
DSA may also be used for a balloon occlusion test [60]. Although 4D-CE-MRA may be useful for evaluating tumour stain in hypervascular brain, head and neck tumours, it is not able to replace DSA in planning interventional procedures [61].
Modern biplane DSA devices are very useful for neurovascular interventions, which also allows: 2D and 3D navigation for advanced embolization guidance; overlay of a DSA reference image over the matching live fluoro for guidance with less contrast media and less dose; cross-sectional imaging to view anatomical structures of tumours in combination with the feeding vessels of the tumour; single-colour vascular flow visualization from a 2D DSA image series to visualize tumour perfusion tumour vascularization, tumour blush and demonstrate postembolization result; to fuse the dataset with a preprocedural CT, MR or PET image to show tumour activity; synchronize the 3D image to the gantry position; PACS connectivity; the reporting of patient exposure following an intervention.
Modern systems update dynamically to movements of the C-arm, table, zoom and source-to-image distance to facilitate efficient workflow during interventional procedures. By providing more effective and faster guidance, this potentially reduces the use of contrast agents and radiation dose. Pulse frequencies can be adapted to clinical needs according to the ALARA principle (As Low as Reasonably Achievable).
DSA (right vertebral angiogram): intra-axial hypervascularized haemangioblastoma supplied mainly by right anterior inferior cerebellar artery.
Radiology has an important role in the diagnosis of brain tumours. A significant factor for success in the treatment of brain tumours is the determination of the extent of the tumour and infiltration of important structures using the CT and MRI imaging methods. Currently, conventional CT protocols, and particularly MRI protocols, have been expanded by sophisticated new techniques that are used in practice. They have significantly contributed to the more detailed species diagnosis of tumours, and to a more accurate estimate of their malignant potential and relationship to the surrounding tissue. With the new techniques, we can evaluate not only detailed tumour morphology, but also the character of the tumour at the microvascular, haemodynamic and cellular level, and the metabolic and biochemical level. With new methods of imaging, exact operational planning approaches on brain tissue can be achieved. Postoperative monitoring of the effect of therapy is highly refined, with more accurate detection of tumour recurrence, and differentiation from postoperative and postradiation changes. Some characteristics of selected brain tumours are presented in Tables 4 and 5.
Hybrid systems have presented new possibilities in brain tumour imaging. The hybrid brain PET/MR allows for molecular, anatomical and functional imaging with uncompromised MR image quality and a high accordance of PET results between PET/MR and PET/CT [62].
\n\t\t\t\t | \n\t\t||||||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tSupratentorial tumours | \n\t\t\tAstrocytoma | \n\t\t\tinfiltrative / non-infiltrative types | \n\t\t\tNo contrast enhancement in low-grade astrocytomas | \n\t\t|
Meduloblastoma | \n\t\t\thighly malignant | \n\t\t\tvariable contrast enhancement | \n\t\t||||
Infratentorial tumours | \n\t\t\tPosterior fossa astrocytoma | \n\t\t\tPilocytic astrocytoma | \n\t\t\tmost common (85% of cerebellar astrocytomas); solid/cystic focal lesion | \n\t\t\twell-demarcated cysts with a contrast enhancing mural nodule | \n\t\t||
Brainstem astrocytoma | \n\t\t\t95% of brainstem neoplasms | \n\t\t\tvariable MR appearance (may be totally or partly solid with a cystic, necrotic, or haemorrhagic component) | \n\t\t||||
Meduloblastoma | \n\t\t\thighly malignant, frequently disseminate into the leptomeninges; cystic components may be present in up to 80%; hydrocephalus is often observed | \n\t\t\tvariable contrast enhancement | \n\t\t||||
Ependymoma | \n\t\t\tarise from the ependyma of the fourth ventricle | \n\t\t\tfoci of high intensity (necrotic areas and cysts) and low intensity (calcifications or haemorrhage) on T2-WI | \n\t\t||||
Haemangioblastoma | \n\t\t\tUncommon except in patients with von Hippel Lindau disease | \n\t\t\tsmall contrast-enhancing nodule with or without cyst | \n\t\t||||
Teratoma | \n\t\t\tin infants, second most commoon type of germ cell tumours, occurs more common in males, may contains calcification, cysts; fatty components can cause a chemical meningitis | \n\t\t\tvariable signal on T1-WI and T2-WI | \n\t\t||||
\n\t\t\t\t | \n\t\t\tSupratentorial tumours | \n\t\t\trare | \n\t\t||||
Sella region | \n\t\t\tCraniopharyngioma | \n\t\t\tmay contain cysts, lipid components, and calcification | \n\t\t\tvariable signal on T1-WI and T2-WI | \n\t\t|||
Infratentorial tumours | \n\t\t\trare | \n\t\t
Characteristics of selected intracranial tumours in children
\n\t\t\t\t | \n\t\t|||||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t\t | \n\t\t\tIntra-axial tumours (located in the brain or brainstem) | \n\t\t\tSupratentorial tumours | \n\t\t\tMTS (metastases) | \n\t\t\tapproximately 33% of intracranial tumours | \n\t\t\tcircumscribed sphenoid peripheral to nodular enhancing lesion, often multiple, axonal oedema | \n\t\t
Glioblastoma | \n\t\t\tmost common primary CNS tumour, highly malignant, can cross corpus callosum | \n\t\t\tirregularly marginated tumour with necrosis and peripheral oedema | \n\t\t|||
Astrocytoma | \n\t\t\tinfiltrative / non-infiltrative types | \n\t\t\tNo contrast enhancement in low-grade astrocytomas | \n\t\t|||
Lipoma | \n\t\t\tbenign fatty lesion commonly affecting corpus callosum | \n\t\t\tdensity of fat, high T1-WI signal, signal suppression on FS (fat suppression) or STIR method | \n\t\t|||
Oligodendroglioma | \n\t\t\tuncommon slow-growing gliomas | \n\t\t\tclump-like calcification | \n\t\t|||
Infratentorial tumours | \n\t\t\tCerebellar metastases | \n\t\t\tespecially lung and breast cancer, also melanoma, thyroid malignancies, and renal cell cancer; can present with obstructive hydrocephalus | \n\t\t\tmelanoma MTS – high T1-WI signal | \n\t\t||
Haemangioblastoma | \n\t\t\ttypically multiple in patients with von Hippel-Lindau disease | \n\t\t\tsmall contrast-enhancing nodule with or without cyst | \n\t\t|||
Lymphoma | \n\t\t\tprimary CNS lymphoma – more common than secondary (can involve the leptomeninges), B cell lymphoma more common; in immunocompromised patients | \n\t\t\tdiffuse leptomeningeal enhancement | \n\t\t|||
Choroid plexus papilloma | \n\t\t\tChoroid plexus papilloma of fourth ventricle, rare neoplasm, usually prominent contrast enhancement, calcifications may be associated, hydrocephalus | \n\t\t\tMR features of choroid plexus carcinoma and papilloma overlap | \n\t\t|||
Extra-axial tumours (arise from the skull, meniges, or tissues other than brain) | \n\t\t\tSupratentorial tumours | \n\t\t\tMeningioma | \n\t\t\tmost common extraaxial tumour, usually benign, multiple in neurofibromatosis type 2 | \n\t\t\tdural-based lesions (the dural tail sign), prominent enhancement, calcifications may be associated | \n\t\t|
Sella region | \n\t\t\tPituitary adenoma | \n\t\t\tcommon benign slow-growing, endocrine abnormalities | \n\t\t\tmicroadenomas typically enhance less than normal pituitary tissue – early phase of dynamic imaging | \n\t\t||
Infratentorial tumours | \n\t\t\tAcoustic schwanoma | \n\t\t\t90% of intracranial schwannomas 75% of lesions in the cerebellopontine angle cisterns multiple seen with neurofibromatosis type 2 | \n\t\t\tprominent contrast enhancement; can be heterogeneous in large lesions | \n\t\t||
Meningioma | \n\t\t\tcan result in compression of dural venous sinuses; rarely invasive – malignant type | \n\t\t\tsame as supratentorial | \n\t\t|||
Paraganglioma | \n\t\t\tlesions, also referred to as chemodectomas, arise from paraganglia | \n\t\t\tprominent contrast enhancement; tubular zones of flow voids; often erosive bone changes | \n\t\t
Characteristics of selected intracranial tumours in adults
Tables 4 and 5 are modified according to [13 – 14, 63 - 64].
Evolution, expansion and transformation of several wild crops via domestication and breeding have blessed the humans and animals with never ending wide varieties of plant-based foods around the globe [1]. Nevertheless, ~ 1 billion population around the world combat with hunger and malnutrition as they are unable to consume important vitamins/minerals thus affecting food and nutritional security in many developing countries [2]. These nutritional deficiencies could be due to the increased inclination towards consumption of specific crops as majority of the peoples relies on wheat, rice and maize for their food [1]. Several lines of literatures have documented that around 50% of total world population relies on above crops for catering while other crops like legumes are cultivated and consumed by marginal communities [3]. The crops cultivated by marginal communities are referred as neglected and underutilised crop species (NUCS) and rich source of vitamins, minerals and secondary metabolites having pharmaceutical properties [4]. These NUCS have the potential to counteract malnutrition by ensuring health/nutritional security, alleviate poverty by increasing resilience and sustainability to the farming systems [1]. However, compare to mainstream crops, less focused have been given towards the genetic improvement of NUCS.
Hyacinth bean (
Furthermore, the seeds of hyacinth bean are also abundant in carbohydrate myoinositol that are exceptional in ovarian function in women by controlling oligomenorrhea and polycystic syndrome [8]. Additionally, the seeds also contain brassinolide which is a steroid which is clinically proven to cure prostate cancer in humans. The alkaloid spermidine found in hyacinth bean seeds is comprehensively used as a biomarker for the perception of skin cancer where as another alkaloid spermine is commonly used in the treatment of cancer/tumours [9]. Trigonelline another alkaloid found in its seed has demonstrated its role in the treatment of diabetes mellitus and also possess antimicrobial property against
Despite of its pharmaceutical/therapeutic importance and catering food requirements of both humans and animals, hyacinth bean still lack focused research for its genomic improvement as compared to other mainstream crops (wheat, rice maize etc.). The genomic improvement through state-of -the art tools and techniques will not only reform its architectural growth but will also pave the way for rewiring the biosynthesis of imperative metabolites which will significantly impact its growth, yield and therapeutic potential. Therefore, this chapter provides valuable insights about the different state-of -the art tools and techniques that can be employed for the genetic improvement of hyacinth bean and how they can be exploited to inspire its therapeutic potential. Further, role of biotic and abiotic elicitors in stimulating the production of important metabolites in hyacinth bean has also been critically reviewed.
Being sessile in nature, plants have to withstand against various adverse climatic conditions to maintain their growth and developmental architecture. The plants are able to survive stressful conditions by synthesising diverse range of secondary metabolites and protease inhibitors that improve their adaptability [13]. Hyacinth bean for example, produces higher level of trypsin inhibitor (14–27 unit/mg) which is a unique property of this orphan legume crop compared to any other major legumes [14]. Like other serine inhibitors, trypsin inhibitor could also function as antifeedant or could also be responsible for strengthening growth, development and productivity by efficiently modulating proteolytic events with in hyacinth bean, mechanism of which has yet to be revealed [15]. Besides this, hyacinth bean also contains wide range of alkaloids, phenols and flavonoids which can be used in treatment of various chronic diseases essentially arthritis, nephritis sepsis as well as skin diseases thus significantly contributing towards human and animal health. All these nutritional and therapeutic properties make hyacinth bean a prime source of food, forage and cash crop in arid and semi-arid areas. However, till date the genes encoding these secondary metabolites are still ambiguous as the crop it self is considered as “orphan crop” for its genome revolution [1]. Further, both conventional and molecular breeding techniques also have been futile in the identification/linking of quantitative trait loci (QTLs) with production of these imperative secondary metabolites [4]. Therefore, all the above information’s have reinstated the need to implement advance omics technology for unleashing the genetic constituent of hyacinth bean and to identify genes/proteins involved in the biosynthesis of important secondary metabolites.
The phytochemicals or secondary metabolites synthesised by various under-utilised crops have the potential to boost innate immune response in humans as well as in animals thus providing immunity against infection, injury and irritation [7]. Several lines of literatures have strongly substantiated that various fruits, vegetables and food legumes synthesise various phytochemicals which are effectively exploited for the treatment of anti-inflammatory disorders, however their mechanism of action is still vague and needs to explored [13]. Various legumes such as soybean, mung bean, moth bean including hyacinth bean have diverted the attention of plant science community due to the presence of functional biological compounds which not only have health benefits and can also be simultaneously used for the treatment of various chronic diseases [8]. Researchers have analysed, tested and confirmed that the crude extracts of mung bean, hyacinth bean and soybean checks the synthesis of nitric oxide (NO) which is an inflammatory mediator thus significantly reducing the ear edema in mice caused by up-accumulation of arachidonic acid [16]. Likewise, another researcher evaluated crude extract of
The phenols present in the dry seeds of legumes such as hyacinth bean have also been implicated to exaggerate anti-inflammatory response upon their adequate consumption [18]. A plethora of research have well indicated that seed and other ethanolic extract of food legumes is rich source of polyphenols and natural antioxidants capable of stimulating anti-inflammatory activity by suppressing the expression of 15-LOX as well as modulating the expression of cyclooxygenase −1 (COX-1) and COX-2 [19]. Similar findings have also been reported by Zhu et al. [16] in pinto bean, black bean and common bean where seed extract was effective in regulating the expression of interlukin-6 (IL-6), interferon-γ (IFN- γ) and IL-17A thus effectively ameliorating acute colitis in mice. In addition to phenolic compounds, these legumes also contain lectins which is protein capable of showing anti-inflammatory response after binding reversibly to carbohydrates [20]. For example, lectins isolated and purified from
The flavonoids such as flavanones, flavanols, anthocyanidins, flavones and isoflavones present in fruits and vegetables have delineated themselves as key players in the treatment of cardiovascular diseases, diabetes and cancers [22]. Various legumes are also a rich source of dietary flavonoids that can regulate carbohydrate digestion, glucose uptake and insulin signalling via various signalling pathways [23]. Among all the flavonoids, dietary isoflavones
Some researchers have also reported neutral to moderate effect of soy food and methanolic extract of hyacinth bean rich in isoflavones in controlling plasma lipid profile thereby confirming anti-diabetic effect of isoflavones could act differentially under
Genistein have also been documented to stimulate the expression of protein kinase A and cAMP cascade which play important role in the proliferation of INS1 and pancreatic β-cells thus efficiently regulating glucose metabolism in mice [31]. However, in addition to isoflavones, anthocyanidin found in soybean seeds rich in cyanidin, delphinidin and petunidin have also demonstrated anti-diabetic effect in streptozotocin induced diabetic rats [32]. Researchers have used methanolic extract of anthocyanidin to diabetic mice and observed that the anthocyanidin effectively raised serum insulin concentration and glucose metabolism in rats. The possible reason behind the anti-diabetic effect of anthocyanidin could be due to the enhance translocation of GLUT4 (glucose transporter) which in turn have stimulated glucose uptake or anthocyanidin could have improved insulin signalling by causing phosphorylation of insulin receptor [33]. Similarly, in another study, researchers have also documented the beneficial effect of anthocyanidin by analysing it on diabetic animal model where they observe that diabetic animal treated with soybean anthocyanidin showed enhanced plasma insulin levels and low triglyceride content [34]. Furthermore, researchers continued their observation up to 12 weeks and observed that the diabetic mice exhibited reduced body weight, blood glucose level, triglyceride levels as revealed by lower expression of lipogenic gene expression in liver and fat [35]. Although, various studies have demonstrated the anti-diabetic effect of both isoflavones and anthocyanidin on animal system, there effect on controlling diabetes in humans are still limited. Therefore, efforts are needed to expand the dimension of research involving structural, biochemical and molecular characterisation of important therapeutic compounds obtained from underutilised legume crops for their efficient use in the human and animal welfare.
The bioactive peptides found in certain legumes and cereals crops has been implicated to regulate growth and development of crops plants by imparting biotic and abiotic stress tolerance [36]. Further, researchers have also isolated and purified some of the plant bioactive peptides and demonstrated their pivotal impact on human health and immune response [37]. Lunasin, a 43 amino acid peptide initially identified and isolated from soybean has shown its tremendous competency in inhibiting cell division in tumour/cancer cells and protect DNA damage by delaying histone acetylation in mammalian cells under oxidative stress [38]. Later, lunasin was also identified in cereals and pseudo-cereals such as rice, wheat, barley and amaranth, however, its present in extremely low quantity as compared to soybean [39]. Being a rich source of lunasin, soybean has been extensively investigated in order to get valuable insight into its structure and function properties, mode action in preventing cancer and the ecological factors that can influence its biosynthesis and transport [37]. Initially, lunasin was identified as chemo-preventive agent but in-depth investigations by several researchers demonstrated that lunasin can effectively suppress skin tumorigenesis in mouse by delaying foci formation in DMBA NIH/3 T3 cells [40].
In addition, researchers have also well documented the chemo-preventive property of lunasin in breast cancer affected mice where they observed significant reduction (30–40%) in tumour cells after treating the mice with lunasin for two months [37]. However, not much research has been focused on lunasin therapeutic properties in soybean as well as in other underutilised legumes still researchers have hypothesised its broad-spectrum role in the treatment of lung cancer, colon cancer and leukaemia [36]. One of the possible mechanisms by which lunasin block cell division in cancer cells could be due to its ability inhibits cell cycle at G2 phase thereby inducing apoptosis in the affected cells [40]. Initial studies on lunasin’s mode of action revealed that it can bind to hypoacetylated histone cores in cancer cells and inhibit acetylation in breast cancer cells and prostrate cancer cells [37]. Recently, researchers have made striking discovery claiming that lunasin binding can suppress the integrin signalling in cancer/tumour cells thereby inhibiting focal adhesion kinase/protein kinase B (FAK/AKT) and extracellular signal-regulated kinase 1 (ERK1) signalling in cancer cells [41]. Certain plant protease inhibitors such as Bowman-Birk inhibitors and flavonoids such as flavon-3-ols found in soybean and other legumes have also demonstrated their role in controlling breast and colon cancer [41]. However, detailed characterisation of their structural and functional properties in many legume crops is still ambiguous and need extensive research by employing advance omics technology for their potential application.
Hypertension is one of the most important factors (apart from diabetes and high cholesterol level) causing cardiovascular disease in humans which is characterised by the increase in systolic/diastolic arterial pressure [42]. Studies have well documented that healthy diet/lifestyle i.e. reduce sodium intake and physical exercise are important factors controlling blood pressure, hypertension and ultimately risk of cardiovascular disease [42]. Various major and underutilised legumes are rich source of secondary metabolites, fibres and micronutrients thus forming an important framework of plant’s bioactive compounds for healthy diet [43]. For example, some bioactive peptides from food as well as grain legumes have demonstrated their potential to combat both hyper and hypotensive effects. Peptides having Glu-Phe, Ile-Arg and Lys-Phe dipeptides identified form legume crops have shown anti-hypertensive effect by inhibiting the activity of Angiotensin-I- Converting Enzyme (ACE) [36, 44]. Similarly, proteins like tyrosinase and lupin present in legume crops have also shown their remarkable ability control both systolic/diastolic blood pressure in peoples suffering from hypertensive disorder [44].
The hypertensive property of both lupin and tyrosinase have also been extensively investigated under in vivo conditions in Goto-Kakizaki rats suffering from hypertension due to excessive consumption of Na rich diet. The researchers fed the hypertensive rats with both lupin and tyrosinase for two weeks and then observed significant reduction in the systolic/diastolic pressure in both the groups [45]. However, lupin treatment also significantly improved endothelium-dependent vasodilation in hypertensive rats more efficiently as compared to tyrosinase [45]. A large body of literatures have also indicated that these bioactive peptides/proteins do not only possess hypertensive and ACE inhibitory effect but are also actively involved in lowering cholesterol and lipid levels [44]. Researchers have also extensively studied hypocholesterolaemia by using bioactive peptides and proteins and identified that the peptide Ile-Ala-Val-Pro-Gly-Glu-Val-Ala was compellingly involved in lowering cholesterol and triglycerides levels by stimulating the activity of bile salts [46]. Furthermore, other studies have also well documented the role of soybean peptides/proteins in efficiently controlling high cholesterol and lipid levels by efficiently modulating ratio of low density/high density lipo-proteins and expression of beta-very-low-density lipoprotein (β-VLDL) receptors thus minimising risk factors for cardiovascular disease [46]. Researchers have identified and evaluated several of these bioactive peptides from other legumes crops as well, however efforts are needed for in-depth characterisation of their function and mode of action in other underutilised legumes such as in hyacinth bean.
Reactive oxygen species (ROS) generated as a consequence of oxidative stress are concomitantly involved in the onset and progression of various chronic diseases. Increased level of ROS has been shown to instigate severe damage to nucleic acids, cause membrane damage via lipid peroxidation and inhibit protein synthesis thus causing cell death or apoptosis [47]. Several crop plants including legumes contains various bioactive compounds such as flavonoids, phenols and some peptides that can efficiently scavenge ROS thus ameliorating stress induced oxidative damages [48]. Flavonoids such as flavanones and flavon-3-ols present in the seeds of certain leguminous plants such soybean and hyacinth bean have been reported to have antioxidative effect as demonstrated by both animal and cell culture studies [49]. In a study conducted by Babu et al. [50] oral infusion of flavanones and flavon-3-ols to an alloxan induced insulin dependent diabetic mouse, significantly enhanced the activity of hepatic catalase, superoxide dismutase and glutathione reductase enzymes thereby confirming their function as antioxidants. Similarly, in another study, researchers orally administered a flavonoid rich compound apigenin to streptozotocin-induced diabetic rats that significant reduction in the triglyceride levels which could be due the antioxidative effect of apigenin that effectively maintained ion/osmotic homeostasis [51]. Moreover, like apigenin, researchers also used anthocyanidin and luteolin treatment to diabetic rats which ultimately protected rat cells from oxidative damage via controlling the synthesis of iterlukin-1β and interferon-γ [52]. Like other flavonoids, anthocyanidin is also extensively present in legume plants which have received significant recognition owing to their health benefits and potential antioxidative properties [52].
Antioxidant peptides like His-Trp-Tyr-Lys have demonstrated to play exceptional role in ameliorating stress induce oxidative damage by efficiently regulating the scavenging of ROS [53]. Moreover, several studies have shown that thiol group of Cys residue can efficiently chelate metallic ions thus lowering the effect of oxidative stress and minimising the onset of chronic disease [53]. A study conducted by Morales-Medina et al. [54] reported that Val and Leu residues present at N-terminus of a peptide and Tyr and Trp residues present at C-terminus of same peptide have antioxidative properties that were effective in minimising lipid peroxidation and strengthening ion homeostasis. Furthermore, it is also well documented that seeds and leaves of legume plants are rich source of other bioactive compounds such as anthocyanins, polyphenols with antioxidative properties and are also capable of performing metal sequestration and stimulate the expression of other stress responsive genes [55]. Additionally, Zhu et al. [56] evaluated various other peptides from soybean and wheat having Leu-Leu-Pro-His-His repeat for its antioxidative activity by using distinct experimental procedure and conditions. The results indicated that the peptide was effective in stimulating 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity, expression of enzymatic and non-enzymatic antioxidants such as catalase, superoxide dismutase, peroxidase and ascorbate thus controlling the level of ROS generation and minimising the chance of severe disease. Lunasin peptide found in soybean and other legume has also been extensively investigated for its antioxidative properties where the researchers documented that lunasin was effective in scavenging both hydrogen peroxide and superoxide anion thereby protecting cell from oxidative damage [42].
Since ancient times legumes have been ascribed to have pharmaceutical/therapeutic values far beyond than providing essential nutrition in the form of amino acids [57]. In recent years, various proteins/peptides form several legume species have been included in the category of nutraceuticals i.e., food or products derived from them having medicinal or therapeutic role in the prevention of disease along with nutritional benefits [57]. Various legume-based bioactive proteins/peptides have been isolated and characterised for their functional role such as Bowman-Birk inhibitors (BBIs), Kunitz inhibitors (KIs) and alpha amylase inhibitors (AAIs) which are also commonly known as anti-nutritional compounds [58]. Several researchers during their early epidemiological studies observed that the protease such as Bowman-Birk inhibitors isolated from soybean seeds were highly effective in the counteracting tumour growth under both
Furthermore, AAIs have demonstrated themselves has a suitable candidate for controlling triglyceride levels thus keeping obesity under check whereas lectins obtained from the seeds of legumes have also shown immense therapeutic potential displaying cytotoxic and anti-cancer activity [60]. For example, concanavalin lectin obtained from the seeds of
Several major and underutilised legumes are rich source of bioactive phenolic compounds or polyhydroxylated compounds with immense anti-nutritional and therapeutic potential [46]. These phenolic compounds also play significant role in the stimulation of immune response, protect cells from oxidative damage and other pathogenic diseases [64]. Several studies have documented that some phenolic compounds isolated from seeds of legume crops are indispensably involved in the treatment of cancer disease, microbial/pathogenic attack, inflammatory disease thus providing potential health benefits [46]. Phenolic compounds are large group of compounds comprising phenolic acids, flavonoids, tannins and stilbenes [64]. Several recent studies have well documented the anti-microbial activity of phenolic compounds obtained from Faba bean, broad bean, adzuki bean and Dolichos bean in their crude methanolic extract of leaf and seeds [65]. The total antioxidant activity (TAA) of methanolic extract of various phenolic compounds and tannins obtained from adzuki bean and lectins have been shown to exhibit anti-microbial activity against several bacterial strains showing average zone of inhibition of 8–20 mm [66]. In addition, these methanolic extract have also shown potential anti-fungal activity against
In addition to phenolic compounds, several bioactive peptides have also been instigated to play important role in regulating various biological activities along with antimicrobial and anti-inflammatory effects [57]. Studies have well reported that several of the ACE-inhibitory peptides containing Arg-Lys residues at C-terminus have shown enhanced anti-microbial activities against pathogenic microorganism [44]. Similarly, peptide containing Leu-Leu-His-His residues also have been shown to posses anti-microbial and anti-oxidative properties. Moreover, a group of researchers working on legume bioactive proteins attempted to used bioactive peptides in conjunction with phenolic compounds and ascertain that the amalgamation of both stimulate the defence mechanisms of plants against pathogenic attack [44]. Similarly, a protein dolichin extracted from hyacinth bean exhibited strong anti-microbial activity against
Plants act as factories that synthesises wide array of nutritional and secondary metabolites with complex structure and functions. Essentially, therapeutic/pharmaceutical secondary metabolites are often extensively isolated and purified from wild plant species or under-utilised crops as compared to cultivated species. However, the chemical synthesis of these medicinally important metabolites is a daunting challenge and is not economically feasible. Recent advancement in the system biology tools have pave the way to exaggerate their synthesis in tissue culture plants, but still their applications are limited to certain plant species because of the complex nature of technological standardisation in respective crops and lack of proper understanding of biosynthetic pathway. In this section, we will be discussing recent advancements made in the system and synthetic biology tools to provide detailed glimpse of the biosynthetic pathways and to explore the unprecedented possibilities of their application for the human welfare. These cutting-edged technologies can be successfully exploited for the improvement/enhancement of secondary metabolites production or could also help in the identification of novel metabolites in cultivated plants as well.
The phenotype exhibited by plants at certain stages of growth/developments are the function of gene × environment interaction that govern a peculiar trait of interest expressed from the plant’s genome [67]. The term “phenotype” corresponds to precise and rigorous recording of the distinct phenotypic parameters from single cell to whole plant level, which if conducted explicitly can help facilitate identification/classification of novel traits in several plant species. Phenomics is a sub-discipline of plant biology that deals with phenotyping under controlled green-house conditions as well as field experimentation using advanced imaging technologies and imaging tools [67]. Phenomics study is a three-step process involving (i) setting up experimental plot, light intensities, nutrition acquisition and temperature (ii) rigorous monitoring/phenotyping such as growth, stress response, photosynthesis, chlorophyll and secondary metabolite contents etc. using advanced imaging tools and (iii) computer-assisted data visualisation, interpretation and storage [68]. Recent technological advancements have paved the way for the development of high-resolution imaging platforms aided with advanced bio-informatic tools for the phenotyping several important traits in plants for cellular and functional analysis [69]. Therefore, phenomics has now been recognised as an indispensable tool that can provide valuable insights into plant’s morphology and physiology which can be further integrated with functional genomics data for analysing key traits such as secondary metabolites production and other economically important traits [68].
Several informatorily databases and analytical toolkits have been developed to facilitate phenomics and taxonomic studies in various cultivated and under-utilised crops at a greater pace. For example., PlantCLEF (2019) is an online repository that contain wide variety of images of plant’s organs with the sole purpose to facilitate identification and classification of underutilised crop plants having distinct features [70]. PlantCLEF act like a real-life computerised program that can identify and classify plant species using raw images by extracting similar traits/characteristics and matching them defined plant species and family [70]. Similarly, MPID (Medicinal plant images database) which is a premium database maintained by Hong Kong Baptist University that is known to accommodate vast range of phenotypic data related to medicinal and therapeutically important plants [71]. Furthermore, in addition to phenotypic data, it also acts as a repertoire of scientific/botanical names, therapeutic values, physiological and ecological parameters of more than 1000 medicinal plants. Likewise, MPDB (Medicinal plant database of Bangladesh) database is also specifically dedicated to store phenotypic and physiological data associated with medicinal and aromatic plants found in Bangladesh [72].
Apart from databases, several computer-based analytical tools and techniques have also been developed and implemented for recording high-resolution images and morpho-physiological parameters in selected plants [70]. Plant computer vision (PlantCV) is a freeware software package written explicitly in python language that provide valuable algorithms for analysing phenotypic data [71]. It can analyse phenotypic data for multiple plant species and compare them with in the database for identification of novel traits/characteristics in genetically un-explored crops [67]. Similarly, ImageJ is a Java based program equipped with various algorithms such as image enhancer, graphic correction, segmentation and measurement to facilitate accurate phenotyping of plant species [73]. HTPheno is an algorithm of ImageJ that allows monitoring of plant’s growth and development in terms colour spectrum. It captures image related to growth and fitness by various angles, time period and temperature/light conditions in the form high-resolution images [74]. However, despite of these technological breakthroughs, the implantation of these state-of-the art techniques are limited certain plant species. Therefore, efforts are needed to establish, standardise and implement these advanced phenomics techniques in various under-utilised medicinally important crops in order to facilitate comprehensive analysis of their physiological, morphological and cellular functions.
Identification of hereditary determinants governing morphological, physiological and biochemical properties are of astute importance to uncover genetic potential of plant species. With the advent of next-generation sequencing techniques it has now become possible to perform in-depth studies on economically/therapeutically important under-utilised crops [75]. Till date whole genome sequencing projects has led to the development of draft genomes and chloroplast genomes of various medicinally important plants which can be efficiently exploited in-conjunction with advanced bio-informatic tools to obtain information about gene families, gene regulatory networks, miRNA and non-coding RNAs involved in gene regulation in those plants whose genome sequence is not available [76]. Furthermore, it can also result in the development of DNA markers for DNA fingerprinting and DNA barcoding to facilitate efficient taxonomic identification of plant under study using specific region of DNA [77]. Several DNA fingerprinting/barcoding primers such as 18-S-rRNA, 5S-rRNA, rupture of the cranial cruciate ligament (rccl), maturase K (matK), internal transcribed spacer (ITS), intergenic spacer (trnH-psbA) have been successfully implemented for identification and classification of medicinal plants. In addition, several dominant and co-dominant markers such as single nucleotide polymorphism (SNP), sequence characterised amplified region (SCAR), amplified fragment length polymorphism (AFLP), inter simple-sequence repeat (ISSR) and random amplified polymorphic DNA (RAPD) have also facilitated identification and authentication of medicinal plants [76].
Transcriptome-wide profiling of genes of regulatory pathways can help researchers gain valuable insight into the functional mechanisms of plant’s biosynthetic pathways. In the recent years, researchers have exploited expressed sequence tags (ESTs) for transcriptome wide analysis of important medicinal plants [77]. Later, the scientists began to use microarray which is probe hybridization-based technique for studying regulation of gene expression and candidate gene discovery [78]. Recently, various transcriptome-wide analysis studies have been conducted in several medicinally important plants and their sequencing and expression profiling data are available in various online databases such as GarlicESTdb (garlic EST database), GEO (gene expression omnibus), ArrayExpress, RASP (RNA atlas of structure probing), AgriSeqDB (RNA sequence database), EGENES (EST database) that can help expedite transcriptomic research in those plants in which transcriptome wide analysis has yet not been completed [79]. Likewise, several toolkits have also been designed that explicitly analyse microarray data and can also be used in conjunction with other phenomics, transcriptomics, proteomics and epigenomics for the identification of functional biological pathways liked with secondary metabolite synthesis [79]. Notably used toolkits are iArray, BRB-Arraytools, KEGG (Kyoto encyclopaedia for genes and genomes), GENEVESTIGATOR, PLEXdb, ExPath are the ones which offers various features for microarray data analysis, visualisation, interpretation and annotation in the form of heat map, graph and tables [80].
In addition, few databases have also been developed such as CroFGD (
Several protein-coding genes have also been qualitatively and quantitatively analysed for their corresponding products to generate a profile of their proteome to help researchers gain valuable insights into the mechanisms underlying cellular and metabolic pathways in medicinal plants [86]. Fewer studies have been conducted to develop a complete proteome map in the medicinal plants describing the proteins involved in the regulation of secondary metabolite synthesis. For example, a study conducted by Jacobs et al. [87] identified various proteins involved in alkaloid biosynthesis in
S. No | Legumes | Genes/Transcription factors (TFs) | Secondary metabolites | Pathway involved | Technique used | References |
---|---|---|---|---|---|---|
1. | Fatty acid desaturase 2 (FAD2) | Linoleic acid | Octadecanoid pathway | Generation of mutant followed by LC–MS analysis | Liu et al. [89] | |
2. | Cytochrome 72A67 (CYP72A67), lateral organ boundaries domain TFs | Saponins | Isoprenoid pathway | Generation of mutant followed by GC–MS | Biazzi et al. [90] | |
3. | Apetella 2/ ethylene responsive factor (AP2/ERF TF) | Quinolizidine alkaloids | Decarboxylation of lysine | Transcriptome de-novo assembly and QTL mapping | Kroc et al. [91] | |
4. | 13-hydroxylupanine O-tigloyltransferase (HMT/HLT), Lysine/ornithine decarboxylase (LDC) and 4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) | Quinolizidine alkaloids | Decarboxylation of lysine | Transcriptome de-novo assembly and QTL mapping | Kroc et al. [91] | |
5. | R2R3-MYB TF (TaMYB14) | Proanthocyanidin | Flavonoid biosynthetic pathway | Gene silencing followed by LC–MS analysis | Hancock et al. [92] | |
6. | MYB TF and MtLAR and MtANR | Proanthocyanidin | Flavonoid biosynthetic pathway | Targeted mutagenesis by HPLC analysis | Cañas and Beltrán [93] | |
7. | Uridine diphosphate glucosyltransferases (UGT73K1 and UGT71G1) | Saponins and isoflavonoids | Triterpenoid saponins biosynthetic pathway | Localization through prokaryotic expression system followed by microarray analysis | Achnine et al. [94] | |
8. | Hyp 1 – Hyp 7 | β-amyrin and mimosine | Triterpenoid saponins biosynthetic pathway | Microarray analysis | Honda and Borthakur [95] | |
9. | TM1624.23 | Phenylpropanoid derivatives and pro-anthocyanidin metabolism | Phenylpropanoid pathway | Gas chromatography coupled to electron impact ionisation/time-of-flight mass spectrometry | Sanchez et al. [96] | |
10. | CaUGT | Isoflavonoids | methylerythritol phosphate pathway | Next generation sequencing followed by marker assisted breeding | Jha et al. [97] | |
11. | Trc genes | Trigonelline, | Tryptophane-kynurenine pathway. | Gene cloning and mutagenesis | Boivin et al. [98] | |
12. | mtPAR, isoflavone synthase (IFS), mtTT8 and mtWD40 1 | proanthocyanidin | Flavonoid biosynthetic pathway | Cloning, gene expression and microarray analysis | Li et al. [99] | |
13. | GmF3H1, GmF3H2 and GmFNSII-1 | Isoflavones | Flavonoid biosynthetic pathway | CRISPR/Cas9-mediated metabolic engineering | Zhang et al. [82, 83] | |
14. | No apical meristem-Arabidopsis transcription activator factor-Cup shaped cotyledon (NAC TF) NAC 4, NAC 29, NAC 25 and NAC 72 | Abscisic acid and secondary metabolite synthesis | Biosynthetic pathway | Multi-OMICS platform | Jha et al. [100] | |
15. | GmCHS1–GmCHS9 | Flavonoids and isoflavonoids | Flavonoid biosynthetic pathway | Cloning, gene expression and microarray analysis | Dastmalchi and Dhaubhadel [101] | |
16. | 2-hydroxyisoflavanone synthase (CYP93C), 2,7,4 0-trihydroxyisoflavanone 4 0-O-methyltransferase/isoflavone 4 0-O-methyltransferase (HI4OMT) and isoflavone-7-O-methyltransferase (7-IOMT) | Flavonoids and isoflavonoids | Flavonoid biosynthetic pathway | Whole genome sequencing, assembly and gene expression | Mochida et al. [102] |
List of putative genes/transcription factors and functional genomics tools involved in regulating biosynthesis of secondary metabolites in legumes.
Metabolomics is also a functional genomics tool with the sole purpose to provide in-depth understanding of different cellular and metabolic pathways in various organisms. Metabolomics is an advanced system biology tool with improved analytical methodologies, sensitivity and resolution that has been successfully exploited to understand biosynthesis of important metabolites in various plant species [103]. Several researchers have used this technique to discover candidate genes/proteins involved biosynthesis of specialised metabolites [104]. Furthermore, it has also provided great depth of understanding about the structural properties and diversity that exists among different metabolites as well as has facilitated to gain valuable insight into the type active ingredients that gives each metabolites its specific nutritional and medicinal properties [103]. Recent decades have witnessed the detailed characterisation of various medicinally important metabolites such as paclitaxel, artemisinin, vincristine, vinblastine, camptothecin and accuminata etc. from Pacific yew tree,
Several metabolomic studies have been conducted in model as well as crop legumes such as
Systemic workflow depicting the application of integrated OMICS tools as well as role of different biotic/abiotic elicitors for improving the biosynthesis known bioactive compounds and identification of novel therapeutic metabolites in legume crops. In this process, tissue culture plants or plants grown in field are treated with different biotic or abiotic elicitors either independently of in combination. The plants are then analysed for the differential expression of genes involved in the regulation of secondary metabolites using integrated OMICS techniques. Candidate genes are discovered using various techniques such as cDNA-AFLP, SAGE, analysed by bioinformatics tools and are rewired using synthetic biology tool. The transformed plants are then exploited for sustainable production of important bioactive metabolites. GWAS: Genome wide association studies; MAS: Marker assisted selection; SNP: Single nucleotide polymorphism; QTLs: Quantitative trait loci’s; miRNA: microRNA; siRNA: Small interfering RNA; NMR: Nuclear magnetic resonance; HPLC: High performance liquid chromatography; GC: Gas chromatography; LC: Liquid chromatography; MALDI-TOF-MS: Matrix assisted laser desorption ionisation-time of flight-mass spectrometry; cDNA AFLP: Complementary DNA amplified fragment length polymorphism (RNA finger printing technique); SAGE: Serial analysis of gene expression; DdPCR: Differential display PCR; SM: Secondary metabolites; CRISPR-CAS 9: Clustered regulatory interspaced short palindromic repeat, CRISPR associated protein 9; TFs: Transcription factors.
In plants, increase synthesis and accumulation of secondary metabolites occur upon their exposure to adverse climatic conditions which not only strengthen their growth but also revamp their innate immune response [107]. Several studies have indicated that distinct physical, chemical and microbial factors could act as abiotic/biotic elicitors for stimulating genes of metabolic pathways which will in turn result in the increase production important/specialised metabolites [108]. Now a day’s elicitation is extensively used as a biotechnological tool to induce the biosynthesis of medicinally important metabolites in various tissues and organs of tissue cultured plants. The functional mechanism behind elicitor’s elicitation involves signal perception by the receptors designed specifically to initiate signal transduction of the genes/transcription factor involved in the biosynthetic pathway (Figure 2) which in turn enhance the production and accumulation of different metabolites [107]. This section briefly describes different biotic/abiotic elicitors that can be employed for enhancing the production of secondary metabolites in medicinal as well as crop plants. A list of different biotic/abiotic elicitors involved in the regulation of bioactive metabolites in legumes are presented in Table 2.
Schematic representation of mechanisms by which biotic/abiotic elicitors signalling pathways involved in the biosynthesis of important bioactive metabolites in plants. The elicitors are perceived by the receptors which then interacts with various components of signal atransduction pathway. This interaction activates certain transcription factors which in turn regulate the expression of various biosynthetic genes/proteins thus stimulating enhanced production of important therapeutic metabolites. SA: Salicylic acid; NO: Nitric oxide; MeJA: Methyl jasmonate; ROS: Reactive oxygen species; CDPKs: Calcium dependent protein kinases; MAPKs: Mitogen activated protein kinases; IP3: Inositol triphosphate; DAG: Diacyglycerol; TFs: Transcription factors.
S. No. | Legumes | Abiotic/biotic elicitor used | Secondary metabolite elicited | Pathway involved | Probable role | References |
---|---|---|---|---|---|---|
1. | Chitosan (0.12%), Salicylic acid (800 μM) and potassium cyanide (400 μM) | Isoflavonoid genistein | Phenylpropanoid pathway | Treatment of cancer, osteoporosis, and ischemic heart disease | Kneer et al. [109] | |
2. | UV light (30-50 W for 5, 10 and 15 hr) | Phenolics and L-Dopamine | Pentose phosphate pathway | Act as neuromodulator and used for treatment of Parkinson’s disease | Shetty et al. [110] | |
3. | UV light (5.5 min at 8000 J m−2), Methyl jasmonate (50 mM), Yeast | Triterpene saponins and other primary metabolites | Phenylpropanoid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Broeckling et al. [111] | |
4. | Methyl jasmonate (at 0.1 kg/m3) | Genistein and Daidzein, and β-glycosidic type isoflavonoids | Phenylpropanoid pathway | Treatment of cancer, osteoporosis, and ischemic heart disease | Gueven and Knorr [112] | |
5. | cadmium (at 10 mg/l) and lead (at 150 mg/l) | 2′-hydroxygenistein glucoside and 2′-hydroxygenistein 7-O-glucoside | Phenylpropanoid pathway | Treatment of cancer, osteoporosis, and ischemic heart disease | Pawlak-Sprada et al. [113] | |
6. | Fungal spore suspension (2 × 106 spores/ml, approximately 5 ml/plant) | Isoflavone phytoalexins or their precursors | Phenylpropanoid pathway | Treatment of cardiovascular disease, osteoporosis, hormone-dependent cancer and loss of cognitive function | Wojakowska et al. [114] | |
7. | Ascorbic acid (500 μM) Folic acid (50 μM) and glutamic acid (5 mM) | Phenolic composition and angiotensin I converting enzyme (ACE) | — | Treatment of hypertension and cardiovascular disease, inhibition of cholesterol synthesis | Dueñas et al. [115] | |
8. | Sucrose, gibberellins and proline | Quercetin-3O-glucoside, malvidin-3O-glucoside, and soyasaponins | Phenylpropanoid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Díaz-Sánchez et al. [116] | |
9. | AgNO3 and H2O2 | Glyceollin and Isoflavones | Phenylpropanoid pathway | Act as anti-tumour, treatment of cardiovascular disease and other chronic diseases | Kalli et al. [117] | |
10. | 6-Prenyl daidzein and phaseol | Phenylpropanoid pathway | Menopausal relief, treatment of osteoporosis, blood cholesterol, and lowering the risk of some hormone-related cancers, and heart disease | Kalli et al. [117] | ||
11. | Arbuscular mycorrhizal fungal inoculum and exogenous methyl jasmonate | Trigonelline and diosgenin | Acetyl coenzyme A through the mevalonate pathway | A novel multitarget based chemo-preventive or therapeutic agent neuroprotective, anti-diabetic | Irankhah et al. [118] | |
12. | Sodium silicate | Flavonoids and phenolic acids | Phenylpropanoid and shikimic acid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Dębski et al. [119] | |
13. | Sodium silicate + Fe EDTA | Flavonoids and phenolic acids | Phenylpropanoid and shikimic acid pathway | Act as anti-tumour, treatment of cardiovascular disease and other chronic diseases | Dębski et al. [119] | |
14. | Sodium silicate | Flavonoids and phenolic acids | Phenylpropanoid and shikimic acid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Dębski et al. [119] |
List of different abiotic/biotic elicitors used for eliciting secondary metabolites production in legume crops.
Biological materials such as proteins, carbohydrates, inactivated enzymes, and polysaccharides etc. whether of plant, fungi or bacterial origin either in crude or purified form is used to induce the synthesis of secondary metabolites are termed as biotic elicitors [120]. Researchers have well indicated that proteins/enzymes are being explicitly used to stimulate the defence system of plants by increasing the synthesis of secondary metabolites involved in the regulation of stress responsive genes [121]. In tissue culture generated plants, several glycoprotein elicitors have been shown to elicit the production of phytoalexin, lectins and agglutinins that tremendously ameliorate the stress-induced oxidative damage [122]. Similarly, various fungal elicitor proteins such as PebC and PevD1 from
Polysaccharides such as xyloglucans, oligogalacturonides, hemicellulose and pectin derived from plant, bacterial or fungal cell wall could also be exploited as an elicitor to stimulate secondary metabolite synthesis in plants [124]. For instance, a polysaccharide derived from
Various phytohormones/signalling molecules such as salicylic acid (SA), nitric oxide (NO) jasmonic acid (JA), ethylene (ET) and abscisic acid (ABA) which can serve as an elicitor to elicit secondary metabolites production and stress-induced defence response in various plant species [127]. Among all, the role of SA, NO and JA have been extensively investigated for the elicitation of secondary metabolites synthesis and imparting resistance against biotic/abiotic stress induced oxidative damage in plants [128]. Methyl-jasmonate a derivative of jasmomic acid precisely activated the production of indole glucosinolate, β-thujaplicin and terpenes indole alkaloids in
Various plant growth promoting rhizobacteria (PGPR) and arbuscular mycorrhizal fungal inoculum in conjunction with methyl jasmonate have been shown to enhance production of various secondary metabolites in
Elicitation of secondary metabolite synthesis by using substance of non-biological such as inorganic salts of heavy metals (VOSO4, NiSO4, CdCl2, AgNO3, CuCl2), UV-radiation, heat, light etc. is known as abiotic elicitation and the substance used are known as abiotic elicitors. Abiotic elicitors such as high temperature, salt, drought, light and heavy metals etc. have also been successfully used as physical and chemical stimuli to elicit the biosynthesis of medicinally important metabolites in various plants [122]. These abiotic elicitors have been successfully used either independently or in combination either by foliar spray, irrigation or as hydroponics under both open field or controlled conditions for secondary metabolite production in medicinally important plants [122]. Present section deciphers the functional mechanism by which these different abiotic based elicitors elicit the production of therapeutically important compounds.
Drought is one of the most prevalent abiotic stress that alter plant growth and productivity around the globe [108]. Researchers have also indicated that in order to cope up with drought induced oxidative stress, plants synthesise certain metabolites such as glycine betaine and proline as mean to strengthen their defence system [122]. Based on this notion, researchers are using mannitol, calcium chloride and polyvinyl pyrrolidone (chemical which are used to induce drought stress) as a physical elicitor to induce the production of terpene indole alkaloids up to 2-fold in treated
Salinity is also known to affect wide array of physiological and biochemical properties in plants thus affecting their growth and development [137]. Prolong exposure to salinity stress causes cellular dehydration and generation of oxidative stress in plants thus limiting their ion/osmotic homeostasis [122]. However, in order to withstand to salinity stress, plants synthesised various secondary metabolites like phenols, alkaloids and terpenes as an ameliorative mechanism to overcome oxidative damage. For instance, researchers observed significant increase in the biosynthesis of terpene indole alkaloids (TIAs) in
High light intensity and temperature are also able to alter the course of secondary metabolites production in plants [138]. Prolong exposure of both high light and temperature can induce oxidative stress in plants that can have adverse effect growth, ontology and development. High temperature can also lead to the induction of premature leaf senescence, stomatal closure and can stimulate transpiration rate to a greater extent [137]. Nonetheless, despite affecting plant’s growth these physical factors have also been reported to stimulate the biosynthesis of important secondary metabolites in the root of
Increasing bioaccumulation of heavy metals such as As, Cd, Cu, Ni, Co and Ag have significantly impacted the agricultural lands and productivity. These heavy metals when presence in excess amount adversely affects plant growth and development [137]. However, at low levels these heavy metals act as co-enzymes/co-factors in various cellular and metabolic pathways thus stimulating secondary metabolite production in plants [122]. Several researchers have well documented the role of heavy metals in stimulating oil content, shikonin/digitalin levels in
In the present era, hyacinth bean has been recognised as an omnipotent legume crop which has the ability to conquer malnutrition, food/hunger index and several chronic diseases all around the globe. Being rich source of genetic and genome resources, the information’s reviewed here can significantly contributes towards unravelling its structural, biochemical and molecular genomics which can lead to the identification of signalling pathways involve in the biosynthesis of important therapeutic metabolites/compounds. Furthermore, the implementation of multi “OMICS” techniques are the need of the hour which can transform hyacinth bean and other underutilised legume crops from being “orphan” to “model crop” by exploiting them in the breeding programs. These underutilised legumes hold the potential for developing sustainable agriculture which can lead to hunger and disease-free world in the era of global warming/pandemic. Therefore, synergistic use of multi OMICS tools are of ultimate requirement for expanding the current horizons of underutilised legume crops to address important problems relevant to Nations be it on health, nutrition and environment.
The authors are also thankful to DST (Department of Science and Technology), and DBT-ISLS facility, BHU, Govt. of India (Grant No. DST/BHU/PURSE 2017-2018 and DST/BHU/FIST 2016-2017) for financial support. KKR is also thankful for financial support in the form of Research Associate by National Academy of Sciences India, Prayagraj is gratefully acknowledged.
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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Taguchi method is a broadly accepted method of DOE, which has proven in producing high-quality products at subsequently low cost.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Rahul Davis and Pretesh John",authors:[{id:"199438",title:"Mr.",name:"Rahul",middleName:null,surname:"Davis",slug:"rahul-davis",fullName:"Rahul Davis"}]},{id:"14634",doi:"10.5772/15998",title:"The Application of FT-IR Spectroscopy in Waste Management",slug:"the-application-of-ft-ir-spectroscopy-in-waste-management",totalDownloads:6652,totalCrossrefCites:18,totalDimensionsCites:34,abstract:null,book:{id:"1574",slug:"fourier-transforms-new-analytical-approaches-and-ftir-strategies",title:"Fourier Transforms",fullTitle:"Fourier Transforms - New Analytical Approaches and FTIR Strategies"},signatures:"Ena Smidt, Katharina Böhm and Manfred Schwanninger",authors:[{id:"20376",title:"Dr.",name:"Katharina",middleName:null,surname:"Böhm",slug:"katharina-bohm",fullName:"Katharina Böhm"},{id:"22840",title:"Dr.",name:"Ena",middleName:null,surname:"Smidt",slug:"ena-smidt",fullName:"Ena Smidt"},{id:"22915",title:"Dr.",name:"Manfred",middleName:null,surname:"Schwanninger",slug:"manfred-schwanninger",fullName:"Manfred Schwanninger"}]},{id:"15157",doi:"10.5772/15959",title:"Fourier Transform Mass Spectrometry for the Molecular Level Characterization of Natural Organic Matter: Instrument Capabilities, Applications, and Limitations",slug:"fourier-transform-mass-spectrometry-for-the-molecular-level-characterization-of-natural-organic-matt",totalDownloads:4351,totalCrossrefCites:6,totalDimensionsCites:34,abstract:null,book:{id:"122",slug:"fourier-transforms-approach-to-scientific-principles",title:"Fourier Transforms",fullTitle:"Fourier Transforms - Approach to Scientific Principles"},signatures:"Rachel L. Sleighter and Patrick G. Hatcher",authors:[{id:"22676",title:"Dr.",name:"Rachel L.",middleName:null,surname:"Sleighter",slug:"rachel-l.-sleighter",fullName:"Rachel L. Sleighter"},{id:"23168",title:"Dr.",name:"Patrick G.",middleName:null,surname:"Hatcher",slug:"patrick-g.-hatcher",fullName:"Patrick G. Hatcher"}]},{id:"60097",doi:"10.5772/intechopen.75381",title:"Robust Optimization: Concepts and Applications",slug:"robust-optimization-concepts-and-applications",totalDownloads:2569,totalCrossrefCites:23,totalDimensionsCites:31,abstract:"Robust optimization is an emerging area in research that allows addressing different optimization problems and specifically industrial optimization problems where there is a degree of uncertainty in some of the variables involved. There are several ways to apply robust optimization and the choice of form is typical of the problem that is being solved. In this paper, the basic concepts of robust optimization are developed, the different types of robustness are defined in detail, the main areas in which it has been applied are described and finally, the future lines of research that appear in this area are included.",book:{id:"6587",slug:"nature-inspired-methods-for-stochastic-robust-and-dynamic-optimization",title:"Nature-inspired Methods for Stochastic, Robust and Dynamic Optimization",fullTitle:"Nature-inspired Methods for Stochastic, Robust and Dynamic Optimization"},signatures:"José García and Alvaro Peña",authors:[{id:"227809",title:"Ph.D.",name:"Jose",middleName:null,surname:"Garcia",slug:"jose-garcia",fullName:"Jose Garcia"},{id:"240407",title:"Dr.",name:"Alvaro",middleName:null,surname:"Peña",slug:"alvaro-pena",fullName:"Alvaro Peña"}]}],mostDownloadedChaptersLast30Days:[{id:"59209",title:"Utilization of Response Surface Methodology in Optimization of Extraction of Plant Materials",slug:"utilization-of-response-surface-methodology-in-optimization-of-extraction-of-plant-materials",totalDownloads:5477,totalCrossrefCites:66,totalDimensionsCites:100,abstract:"Experimental design plays an important role in several areas of science and industry. Experimentation is an application of treatments applied to experimental units and is then part of a scientific method based on the measurement of one or more responses. It is necessary to observe the process and the operation of the system well. For this reason, in order to obtain a final result, an experimenter must plan and design experiments and analyzes the results. One of the most commonly used experimental designs for optimization is the response surface methodology (RSM). Because it allows evaluating the effects of multiple factors and their interactions on one or more response variables it is a useful method. In this section, recent studies have been compiled which aim to extraction of plant material in high yield and quality and determine optimum conditions for this extraction process.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Alev Yüksel Aydar",authors:[{id:"218870",title:"Dr.",name:"Alev Yüksel",middleName:null,surname:"Aydar",slug:"alev-yuksel-aydar",fullName:"Alev Yüksel Aydar"}]},{id:"74096",title:"Time Frequency Analysis of Wavelet and Fourier Transform",slug:"time-frequency-analysis-of-wavelet-and-fourier-transform",totalDownloads:1291,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Signal processing has long been dominated by the Fourier transform. However, there is an alternate transform that has gained popularity recently and that is the wavelet transform. The wavelet transform has a long history starting in 1910 when Alfred Haar created it as an alternative to the Fourier transform. In 1940 Norman Ricker created the first continuous wavelet and proposed the term wavelet. Work in the field has proceeded in fits and starts across many different disciplines, until the 1990’s when the discrete wavelet transform was developed by Ingrid Daubechies. While the Fourier transform creates a representation of the signal in the frequency domain, the wavelet transform creates a representation of the signal in both the time and frequency domain, thereby allowing efficient access of localized information about the signal.",book:{id:"10065",slug:"wavelet-theory",title:"Wavelet Theory",fullTitle:"Wavelet Theory"},signatures:"Karlton Wirsing",authors:[{id:"325178",title:"Dr.",name:"Karlton",middleName:null,surname:"Wirsing",slug:"karlton-wirsing",fullName:"Karlton Wirsing"}]},{id:"60864",title:"Statistical Methodology for Evaluating Business Cycles with the Conditions of Their Synchronization and Harmonization",slug:"statistical-methodology-for-evaluating-business-cycles-with-the-conditions-of-their-synchronization-",totalDownloads:1377,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The importance of the topic of business cycle research and their interaction is due to the fact that the cyclical nature of development is a universal feature of the market economy (regardless of the level of development of the country’s economy and the principles of its organization). In all cases, cyclical ups and downs depend not only on internal system cyclical processes and their factors in countries but also on the consequences of intercountry interaction. The ability to measure and predict business cycles, taking into account their mutual influence, is a prerequisite for the development of an adequate business policy of countries and their associations.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Elena Zarova",authors:null},{id:"54366",title:"Solution of Differential Equations with Applications to Engineering Problems",slug:"solution-of-differential-equations-with-applications-to-engineering-problems",totalDownloads:6882,totalCrossrefCites:5,totalDimensionsCites:8,abstract:"Over the last hundred years, many techniques have been developed for the solution of ordinary differential equations and partial differential equations. While quite a major portion of the techniques is only useful for academic purposes, there are some which are important in the solution of real problems arising from science and engineering. In this chapter, only very limited techniques for solving ordinary differential and partial differential equations are discussed, as it is impossible to cover all the available techniques even in a book form. The readers are then suggested to pursue further studies on this issue if necessary. After that, the readers are introduced to two major numerical methods commonly used by the engineers for the solution of real engineering problems.",book:{id:"5513",slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Cheng Yung Ming",authors:[{id:"191017",title:"Dr.",name:"Cheng",middleName:null,surname:"Y.M.",slug:"cheng-y.m.",fullName:"Cheng Y.M."}]},{id:"56538",title:"Stochastic Resonance and Related Topics",slug:"stochastic-resonance-and-related-topics",totalDownloads:1719,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The stochastic resonance (SR) is the phenomenon which can emerge in nonlinear dynamic systems. In general, it is related with a bistable nonlinear system of Duffing type under additive excitation combining deterministic periodic force and Gaussian white noise. It manifests as a stable quasiperiodic interwell hopping between both stable states with a small random perturbation. Classical definition and basic features of SR are regarded. The most important methods of investigation outlined are: analytical, semi-analytical, and numerical procedures of governing physical systems or relevant Fokker-Planck equation. Stochastic simulation is mentioned and experimental way of results verification is recommended. Some areas in Engineering Dynamics related with SR are presented together with a particular demonstration observed in the aeroelastic stability. Interaction of stationary and quasiperiodic parts of the response is discussed. Some nonconventional definitions are outlined concerning alternative operators and driving processes are highlighted. The chapter shows a large potential of specific basic, applied and industrial research in SR. This strategy enables to formulate new ideas for both development of nonconventional measures for vibration damping and employment of SR in branches, where it represents an operating mode of the system itself. Weaknesses and empty areas where the research effort of SR should be oriented are indicated.",book:{id:"6128",slug:"resonance",title:"Resonance",fullTitle:"Resonance"},signatures:"Jiří Náprstek and Cyril Fischer",authors:[{id:"207472",title:"Dr.",name:"Jiri",middleName:null,surname:"Naprstek",slug:"jiri-naprstek",fullName:"Jiri Naprstek"},{id:"213311",title:"Dr.",name:"Cyril",middleName:null,surname:"Fischer",slug:"cyril-fischer",fullName:"Cyril Fischer"}]}],onlineFirstChaptersFilter:{topicId:"15",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83171",title:"Some Results on the Non-Homogeneous Hofmann Process",slug:"some-results-on-the-non-homogeneous-hofmann-process",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.106422",abstract:"The classical counting processes (Poisson and negative binomial) are the most traditional discrete counting processes (DCPs); however, these are based on a set of rigid assumptions. We consider a non-homogeneous counting process (which we name non-homogeneous Hofmann process – NHP) that can generate the classical counting processes (CCPs) as special cases, and also allows modeling counting processes for event history data, which usually exhibit under- or over-dispersion. We present some results of this process that will allow us to use it in other areas and establish both the probability mass function (pmf) and the cumulative distribution function (cdf) using transition intensities. This counting process (CP) will allow other researchers to work on modelling the CP, where data dispersion exists in an efficient and more flexible way.",book:{id:"12021",title:"Applied Probability Theory - New Perspectives, Recent Advances and Trends",coverURL:"https://cdn.intechopen.com/books/images_new/12021.jpg"},signatures:"Gerson Yahir Palomino Velandia and José Alfredo Jiménez Moscoso"},{id:"83034",title:"Optimal N-of-1 Clinical Trials for Individualized Patient Care and Aggregated N-of-1 Designs",slug:"optimal-n-of-1-clinical-trials-for-individualized-patient-care-and-aggregated-n-of-1-designs",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106352",abstract:"Precision medicine typically refers to the use of genomic signatures of patients to assign more effective therapies to treat patients, or, for improved diagnosis of the early onset of a disease so that interventions can be delivered to prevent or delay the disease progression. Because the aim is to provide individualized patient treatment, such single-person trials are called N-of-1 trials. This chapter reviews fundamental ideas, models, and construction of optimal designs for N-of-1 trials, which are invariably constructed from crossover trials, where each patient receives a random sequence of trial treatments over time. We construct examples of universally optimal N-of-1 designs for comparing two treatments under various correlation structure assumptions and discuss how N-of-1 trials may be combined to form optimal aggregated N-of-1 trials for assessing average treatment effects for two or more treatments.",book:{id:"10678",title:"Biostatistics",coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg"},signatures:"Yin Li, Weng Kee Wong and Keumhee Chough Carriere"},{id:"83029",title:"Quasi Conformally Flat Quasi Einstein-Weyl Manifolds",slug:"quasi-conformally-flat-quasi-einstein-weyl-manifolds",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105683",abstract:"The aim of this work is to study on quasi conformally flat quasi Einstein-Weyl manifolds. In this book chapter, firstly, an interesting relationship between complementary vector field and generator of the quasi Einstein-Weyl manifold is obtained and supported by an example. Then, it is investigated that quasi conformally flat quasi Einstein-Weyl manifolds are of quasi constant curvature, recurrent and semi-symmetric under which conditions after obtaining the expression of the curvature tensor of the quasi conformally flat quasi Einstein-Weyl manifold. Furthermore, some equivalences are obtained between to be of quasi constant curvature and to be semi-symmetric in quasi conformally flat quasi Einstein-Weyl manifolds.",book:{id:"11502",title:"Manifolds - Recent Developments and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11502.jpg"},signatures:"Fusun Nurcan"},{id:"82970",title:"Probability to be Involved in a Road Accident: Transport User Socioeconomic Approach",slug:"probability-to-be-involved-in-a-road-accident-transport-user-socioeconomic-approach",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.106325",abstract:"Road education is one of the most relevant issues focused to reduce traffic accidents, so it is important to analyze the driver’s behavior on the roads. International research has found evidence for a relationship between socioeconomic characteristics and traffic accidents. In this sense, the chapter shows a methodology to estimate the probability to be involved in a road accident, considering the road education and the socioeconomic characteristics of the population of a specific region, taking the Santiago de Querétaro city (in México) as a study case. Through a logit model estimation and a survey applied to pedestrian, cyclist, motorcyclist, car driver, and freight driver allow us to determine which socioeconomic variables and road education are significant to determine the probability of being involved in a road accident.",book:{id:"12021",title:"Applied Probability Theory - New Perspectives, Recent Advances and Trends",coverURL:"https://cdn.intechopen.com/books/images_new/12021.jpg"},signatures:"Saúl Antonio, Obregón Biosca, José Luis Reyes Araiza and Miguel Angel Pérez Lara y Hernández"},{id:"82947",title:"Some Tauberian Theorems under Triple Statistically Nörlund-Cesáro Summability Method",slug:"some-tauberian-theorems-under-triple-statistically-n-rlund-ces-ro-summability-method",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.106141",abstract:"In this paper, we extend the notion presented by Braha (2020) in a higher dimension, we introduce the notion of Np,qn,m,gCn,m,g1,1,1-statistically convergence and show necessity and sufficiency conditions under which the existence of the limit st-limn,m,g→∞xn,m,g=L follows from that st-limn,m,g→∞Np,qn,m,gCn,m,g1,1,1=L. These conditions are one-sided or two-sided if xn,m,g is a sequence of real or complex numbers, respectively.",book:{id:"11503",title:"Functional Calculus - Recent Advances and Development",coverURL:"https://cdn.intechopen.com/books/images_new/11503.jpg"},signatures:"Carlos Granados"},{id:"82847",title:"A Chaos Auto-Associative Model with Chebyshev Activation Function",slug:"a-chaos-auto-associative-model-with-chebyshev-activation-function",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106147",abstract:"In this work, we shall put forward a novel chaos memory retrieval model with a Chebyshev-type activation function as an artificial chaos neuron. According to certain numerical analyses of the present association model with autocorrelation connection matrix between neurons, the dependence of memory retrieval properties on the initial Hamming distance between the input pattern and a target pattern to be retrieved among the embedded patterns will be presented to examine the retrieval abilities, i.e. the memory capacity of the associative memory.",book:{id:"12019",title:"Chaos Theory - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/12019.jpg"},signatures:"Masahiro Nakagawa"}],onlineFirstChaptersTotal:43},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:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:333,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",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. 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",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"August 17th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Rosa María Martínez-Espinosa is a Full Professor of Biochemistry and Molecular Biology at the University of Alicante, Spain, and has been the vice president of International Relations and Development Cooperation at this university since 2010. She created the research group in applied biochemistry in 2017 (https://web.ua.es/en/appbiochem/), and from 1999 to the present has made more than 200 contributions to Spanish and international conferences. Furthermore, she has around seventy-five scientific publications in indexed journals, eighty book chapters, and one patent to her credit. Her research work focuses on microbial metabolism (particularly on extremophile microorganisms), purification and characterization of enzymes with potential industrial and biotechnological applications, protocol optimization for genetically manipulating microorganisms, gene regulation characterization, carotenoid (pigment) production, and design and development of contaminated water and soil bioremediation processes by means of microorganisms. This research has received competitive public grants from the European Commission, the Spanish Ministry of Economy and Competitiveness, the Valencia Region Government, and the University of Alicante.",institutionString:"University of Alicante",institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. 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He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. 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She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. 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He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. 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