Advantages and limitations of protein microarrays in biomedicine.
\r\n\t
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\nThe current interest in protein microarrays due, mostly in part, to the prospects that proteomics assays, based on them, allow: deciphering the altered protein expression in different levels (tissue, cells, subcellular structures, body fluids, protein complexes,…); the development of novel biomarkers for diagnosis or early detection of diseases; the identification of new targets for therapeutics; and accelerating drug development through more effective strategies to evaluate therapeutic effect and toxicity [1].
\nMainly based on the proteome alterations in disease may occur in many different ways that are not predictable from genomics analysis, and it is clear that a better understanding from genomic analysis together with an substantial impact in biomedicine.
\nRecently, there is a large amount of protein microarray approaches available for applications related to disease because the employment of these technologies is very useful for better diagnostics and to shorten the path for developing effective therapy. In general, protein microarrays allow to increase sensitivity, reduce sample requirement, increase high-throughput and identify protein alterations (quantitative and qualitative), such as post-translational modifications.
\nIf we want to quantify thousands of proteins in a small number of samples, a typical proteomics discovery experiment employs a non-targeted approach (shot-gun proteomics). The hundreds of proteins that result from the comparative analysis, are differentially expressed between healthy and diseased samples. After discovery phase, the potential biomarkers proteins are reduced by performing studies on additional patients or at more time points, and/or by using another technique. Then, these potential biomarkers are verified on a set of 10–50 clinical samples. In the final step, a small number of biomarkers is “validated” on 100–500 clinical samples. Bearing in mind this conventional biomarker workflow, high-throughput assays are required in order to overcome the gap between translational research and clinical needs (from bench to the bedside) [1] (Figure 1).
\nStages in the development of a biomarker.
Biomarkers or biological markers are defined as measurable characteristics that indicate the state of a biological process, differentiating if it is normal or pathological. They are all those molecules that are found in body fluids in low abundance and that are associated with specific health or disease processes [2]. The methodology to establish that a biomarker is good for clinical application is divided into three steps: discovery, verification and validation as it has been said before [3, 4].
\nProteomics, the scientific discipline that studies proteins, has identified several proteins that can act as biomarkers. There are several techniques that use biomarkers and that allow an early diagnosis of the disease. These include new generation sequencing, mass spectrometry and protein arrays [5, 6]. In this chapter we will focus on the study of arrays.
\nMicroarray technology is a term that refers to the miniaturization of thousands of assays in a single device, allowing the simultaneous and massive analysis of a large number of biomolecules in a single biological sample. They allow the study of a large number of parameters in a single test with a minimum requirement of sample and reagents, which is why they constitute a simple, fast and very sensitive sampling technique [7, 8].
\nThe microarrays present several innovative strategies for their applications such as the identification of biomarkers and the interactions between proteins that may help in the future to routine clinical analysis.
\nThere is a great variety of arrays which can be classified according to their content in protein microarrays, functional protein arrays and reverse phase arrays; according to their shape in planes and spheres; and also according to their detection method.
\nIn this chapter we will explain all these types of arrays, some of their applications in biomarker discovery as well as validation/verification.
\nA biomarker is defined by the Food and Drug Administration (FDA) as “A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.”
\nIt is possible to distinguished three categories depending on the application of the biomarker: diagnostic biomarkers used for disease detection, prognostic biomarkers used for predict the course of a particular disease such as, recurrence, progression, and survival and predictive biomarkers used for predict the response to treatment that could be subsequently applied in patient assessment [1].
\nDuring last years, biomarker research and its translation into the clinics have been accelerated by protein microarrays due to the extraordinary capacity for identifying of valuable biomarkers in a short period of time without the requirement of any prior in-depth knowledge into the mechanism of disease progression.
\nMoreover, protein microarrays are reliable for analyzing targeted/non-targeted biomarkers presented in mostly of human proximal body fluids (such as plasma, serum, synovial liquid,…) with a wide dynamic range. In contrast with other proteomic strategies, protein microarrays avoid the sample pre-fractionation. Thus, for example, serum, plasma, urine and tissue extracts which are complex and non-fractionated proteome mixtures, could be used for experimentation. For this reason, among others, protein microarrays offer a powerful technology for functional proteomics analysis in HT format.
\nMicroarray technologies, like DNA arrays, printed dense spots of capture ligands immobilized onto a solid support that are exposed to samples containing corresponding binding molecules (often called queries), allowing the simultaneous analysis of thousands of capture targets within the same assay. Ekins and collaborators described these binding events based on miniaturization as the key parameter. They predict that a system that uses small amounts of capture molecules and a small amount of sample could be more sensitive than a system using a hundred times more material. In fact, this is the case when K < 0.1 (where K is the affinity constant between ligand and target) [9].
\nThe capture ligand is presented in a confined area of array, reducing its diffusion. The specific binding event with its target takes place with the highest signal intensities and optimal signal-to-noise ratio could be achieve in these small spots [9] (Figure 2). An immunoassay in an array format displays sensitivities in the pM to fM range, enabling test low-abundant (pg/mL) analytes in crude proteomes with a small volume of sample. In many cases, protein microarrays show a relevant advantage in clinical applications because the samples to test are minimal [10].
\nProcess of microarray technology.
For that reason, protein array technology needs to use a multiplex and highly sensitive protein assay capable of handling and resolving complex proteomes with limited available sample [10].
\nRecently, several types of protein microarrays have been developed and applied as multiplex throughput assay in several biological characterization. Here, it is described the principal features of protein microarrays.
\nIn general, protein microarrays are classified according to features such as content, format, detection method and according to final application such as analytical and/or functional. Here, it is described the main aspects of the different types of protein microarrays.
\nIn general, there are three types of arrays according to their content:
\nIn these arrays, antibodies are printed onto array surface and used multiplexed affinity reagents to detect and quantify proteins in complex biological samples [8, 11].
\nIt is based on the antibody antigen interaction. Antibodies have the ability to bind to a very specific protein, so particular or rare analytes can be detected in highly heterogeneous mixtures. They are usually used to identify biomarkers which predict a biological condition such as healthy or pathologic.
\nSo many studies have shown that only a fraction of antibodies may properly work and this may be due to the loss of antibody activity by degradation or denaturation on storage or during the printing process, or due to inappropriate antibody orientation onto the array surface [7].
\nIt is based in the identification of protein interactions with different molecules (proteins, DNA, lipids, drug, etc.), so recombinant proteins are printed onto array surface.
\nSome examples are protein in situ array (PISA), printing arrays from DNA (DAPA) nucleic acid programmable protein array (NAPPA) and multiplexed nucleic acid programmable protein array (M-NAPPA). They are essential for pharmaceutical industry because they allow to know protein interactions [11].
\nPISA is based on DNA amplified by PCR as a template. The DNA that encode the protein of interest contains a T7 promoter or another strong transcriptional promoter and an in-frame N-12 or C-terminal tag sequence for protein capture onto the surface. PISA offers the possibility to cell-free production of protein arrays. It means protein are produced using cell extracts directly on the surface os arrays. PISA demonstrated that multiple proteins could be produced without the need of using cells for expression followed by lysis and purification to make the proteins [11].
\nDAPA is a technique derived from PISA, but DAPA allows use the same DNA template slide repeatedly for printing up to 20 copies of the same protein and also DNA could be reused after prolonged periods of time. DAPA takes a long time to express proteins due to the diffusion of proteins through the membrane. This technique starts by spotting the PCR amplified DNA fragments encoding the tagged protein on one slide. This slide is sandwiched with another Ni-NTA slide where a tag-capturing agent immobilizes the expressed protein. A permeable membrane with the cell-free lysate which allows coupled transcription and translation is places between the two slides. Then, the expressed proteins are captured to the surface on the other slide through the capture ligand. Overall, DAPPA requires long time to express proteins and this technique presents the protein diffusion as strong limitation, in particular with large proteins [7, 9, 11, 12].
\nNAPPA uses cDNA templates cloned into expression plasmids which adds a transcriptional promoter and also an in-frame polypeptide capture tag. It has several advantages: (1) once the clone is produced as a glycerol stock it becomes an indefinitely renewable resource that could be shared with other labs; (2) if the clone is carefully sequence verified, then the resource will have long-term sequence fidelity; (3) the use of plasmids removes some of the length constraints on the epitope tags, so that functional protein tags can be used. There are many applications of NAPPA where the proteins are fused with glutathione-S-transferase (GST); nevertheless, other tags such as flag, HA, c-myc, and Halo tag have been used in specific applications. High quality supercoiled plasmid DNA is purified from bacteria cultures and printed onto an activated ester surface along with a homo-bifunctional crosslinker, bovine serum albumin (BSA) and anti-GST antibody. BSA efficiently increased the DNA binding and narrows down the unspecific interactions and anti-GST attaches the protein expressed. When cell-free expression system is added to the array, a coupled transcription/translation reaction is produced and the nascent protein is linked to the capture agent tag the C-terminal end assuring the complete translation of the protein [10, 11, 13].
\nPuromycin capture protein arrays (PuCA) are cell-free expression protein arrays based on the affinity of puromycin by expressed peptide/protein. First, PCR DNA is transcribed to mRNA, and a single-stranded DNA oligonucleotide modified with biotin and puromycin on each end is then hybridized to the 3′-end of the mRNA. The mRNAs are placed on a slide and immobilized by the binding of biotin to streptavidin which is previously coated on the slide. Cell extract is then dispensed on the slide for in situ translation to take place. When the ribosome reaches the hybridized oligonucleotide, it stops and incorporates the puromycin molecule to the nascent polypeptide chain, thereby attaching the newly synthesized protein to the microarray through the DNA oligonucleotide [14].
\nM-NAPPA is based on combining up to five different DNA plasmids at one point. This increases the number of proteins displayed by microarrays by five. It also reduces the cost and the time spent in work. M-NAPPA would be useful in unbiased HT screening studies, such as protein-protein interactions, protein-DNA interactions, discovery of drug binding target as well as (auto)antibody biomarkers for a variety of human diseases [15].
\nIn these arrays, biological samples, tissues and cell lysates are printed onto array surface. The detection is accomplished by antibodies link with specific proteins, and then link with another antibody with fluorescence. They offers the potential for rapid comparison of the levels of such proteins present among a significant number of samples on a single array [7, 8].
\nThe problem is the interaction of the lysate matrix, therefore validated antibodies should demonstrate no cross-reactivity toward other biomolecules of the lysate (Figure 3).
\nArrays according to their nature of the capturing agent.
Planar arrays are based on high-density microspots of ligand deposited onto a solid support and separated by a minimal distance. It is necessary to know some parameters that influence in the assay performance like spot size and morphology, ligand capacity, background signal, limit of detection and spot reproducibility [13].
\nMicrosphere arrays are based on the simultaneous use of different populations of microspheres labeled with several fluorochromes. Each one is covered by different antibodies in order to incubate a biological sample of interest [7].
\nDepending on the detection method it is classified in methods based on labels and free-label methods [7].
\nAmong them are radioisotopes and conventional fluorochromes like fluorescein, BODIPY or cyanins. Cyanines are the most used in protein arrays due to its minimal interaction with other biomolecules and its high intensity. More than two fluorochromes can be combined to identify several biomarkers at the same time. It is used for cancer biomarkers.
\nFlow cytometry can be used to detect soluble proteins present in body fluids or in cell lysates using microspheres. The CF has two lasers for the analysis quantitative and qualitative that allows to know the binding of target proteins with the microspheres. Comparing conventional fluorescent techniques, flow cytometry allows rapid and accurate quantitative-qualitative evaluation of a high number of proteins, with low cost and high sensitivity.
\nThese systems are an union of magnetic spheres with antibodies that allow the detection of proteins. They capture soluble proteins with high reproducibility and sensitivity, associated with low background noise, a wide dynamic range and low cost.
\nThe “Quantum dots” (QDs) are nano-crystals, formed by a core of semiconductor and fluorescent material coated with another semiconductor, which have very stable optical properties and a large gap between the wavelengths of emission and excitation of the complement. These nanometric particles could work like labels joining with peptides or antibodies for the recognition of cellular components. They have a high fluorescence, greater photo-stability, multicolored excitation, an adjustable and narrow emission spectrum, and their higher quantum yield, compared with organic fluorochromes. They also have several disadvantages like its high susceptibility to oxidation and photolysis as well as some risks for human health and the environment. They are used to localize tumor biomarkers.
\nGold nanoparticles are used in protein arrays due to their optical properties, quantum efficiency and compatibility with a wide range of wavelengths.
\nThis technology is based on the generation of plasmons on a surface, which are oscillations of free electrons propagated parallel to the metal/medium interface, which allows to measure the changes in the refractive index of the sensor surface. The intensity variation of the reflected light and/or the angle of incidence tell us if there are molecular associations or dissociations, allowing to determine the relationship between the association and dissociation of biomolecules with each other. In addition, the SPR technology also allows evaluate the affinity and specificity of these interactions, facilitating the measurement of biomolecular interactions in real time with high sensitivity.
\nMicrocantilevers are thin sheets of silicon coated with a gold surface associated with nanomechanical systems of biomolecular recognition. For this reason, the antibodies or proteins are immobilized on said sheets, so that when there is an interaction between these molecules and their possible ligands we can measure the variation in the position of the sheet using different optical or electronic systems.
\nIt is a microscopic analysis observing only the topological variations of the surface of an object. It has been used for the evaluation of the immobilization of biomolecules with a micrometric resolution, and for the detection of protein interactions on the arrays surface.
\nBearing in mind the final application, protein microarrays are classified into two categories: Analytical arrays and functional arrays.
\nThese arrays are normally used to quantitatively identify the presence of multiples protein in one single assay. Commonly, the main application is the detection of differently expressed proteins and their abundance in different samples. Biomarkers are determined by this type of arrays. They are biometric measurements, including molecular signatures, that predict a biological or clinical condition for example, normal or pathologic, often with potential diagnostic or prognostic value [9, 10, 16].
\nThese arrays are mainly used for the characterization and identification the specific function of proteins, as well as their interactions with other molecules (including proteins, peptides, small molecules/drug, enzyme/substrates or nucleic acids,…) [12, 17]. Moreover, functional protein arrays also allow the detection and identification of post-translational modifications (PTMs), such as glycosylation, phosphorylation, acetylation,… which typically modulate the proteins’ function, regulation and/or turnover.
\nRefers to research, functional protein arrays present the detection of multiple protein interactions with low reagent consumption in a fast and low cost fashion. On the translational side, the discovery of these interactions will promote the progress of new pharmaceutical targets, diagnostics and therapeutics. As a consequence, this technology is very interesting in the pharmaceutical industry [10] (Table 1).
\nAdvantages and limitations of protein microarrays in biomedicine.
During last decade, protein microarrays have been successfully employed in multiplex detection for biomarker discovery; here, it is remarked a few of these studies in order to illustrate the utility of these approaches in the field.
\nHaab et al. defined a panel of five serum proteins significantly expressed in serum between prostate cancer patients (33) and 20 controls [18]. In addition, this team has also identified 84 proteins with differentially relative abundance between diagnosed lung cancer patients and healthy controls [19].
\nIn a similar approach, Wittekind and colleagues reported a set of proteins as biomarker candidates associated with hepatocellular carcinoma [20]. Nowadays, several studies have been performed and focused on biomarker identification in several oncological pathologies; for example: In ovarian cancer, 11 proteins have been identified by Amonkar et al. [21]; Sreekumar et al. identified a panel of proteins as biomarker candidates in colon carcinoma cells [22]; Díez et al. has identified differentially expressed proteins in B-cell chronic lymphocytic leukemia which are related with target therapeutics [23]. Previously, Below and coworkers have developed an antibody microarray to immunophenotype 1100 leukemia and lymphomas according to the abundance of a panel of 82 antigens or cluster of differentiation (CD) characterized at the surfaces of lymphocytes [24].
\nIn 2014, the firstly reported study about pathogen-host protein interactions by CID and workers. In this work, they studied the presence of post-transcriptional modifications in effector proteins, T3SS proteins, from different mutants of
Another similar study, performed by Li and coworkers, has been published about identification of 149 antigens from
In 2009 Thanawastein et al. developed an approached called Expressed protein screen for immune activators (EPSIA) which were successfully applied in the identification of novel bacterial immunostimulatory proteins from
Recently, Manzano et al. reported a set of novel vaccine candidates for
In a most recent study, Montor et al. describe a work using NAPPA arrays to evaluate candidate membrane antigens in
In response to many pathological processes, the humoral immune system generates antibodies to self-proteins (“auto-antibodies”). These auto-antibodies are generated due to antigen over-expression, mutation, altered post-transcriptional modifications of altered degradation released from damaged tissue which lead to their recognition by the immune system. Auto-antibodies have several benefits which make them as suitable source of biomarkers: (1) They have been discovered before the appearance of clinical symptoms; (2) They are simple to identify even at low levels once their target antigen is known; (3) they are easy to reunite from blood; and (4) they could be show in higher levels and with a longer half-life than their target antigens, which may only be present in transiently in blood [10].
\nFor example, NAPPA arrays were used for serological screening for the first time in 2007 by Anderson et al. They investigated the presence of antibodies against tumor antigens in breast cancer. The tumor-suppressor p53 is well-characterized in several solid tumors and the presence of antibodies against p53 is mainly due to mutations in its gene which lead to alterations in its half-life. By this approach, the authors presented that p53-specific antibody levels were significantly lower in healthy donors than in breast cancer patients and the response to p53 antigen was detected in Stage II disease. Also they studied that the antigen sites of p53 with several antibodies which recognized distinct epitopes of the protein to confirm that many regions of the protein expressed in NAPPA were accessible to antibodies in serum detected to them [10, 30].
\nIn a follow-up work, also this group performed a wide screen for new auto-antibodies in breast cancer. They designed and developed 4988 candidate antigens to detect their auto-antibodies in serum samples from breast cancer patients with stage I–III disease. This screening was performed in three stage design that entailed comparing cases and controls and eliminating uninformative antigens at each stage. At the final phase, slightly more than 100 antigens were tested and 28 auto-antibodies were identified that distinguished benign breast disease from invasive cancer under blinded conditions [10, 30].
\nWith a similar workflow, Labaer et al. developed a pilot NAPPA to assess auto-antibodies present in juvenile idiopathic arthritis (JIA) which is a disease characterized by chronic joint inflammation in children [31].
\nRecently, Fuentes’s lab has performed a screening of auto-antibodies in osteoarthritis and arthritis rheumatoid by using NAPPA arrays and validated with other protein arrays technologies [32].
\nA decade ago, Labaer and colleagues evaluated functional properties of the proteins IVTT expressed onto the array by performing protein-protein interactions in high-throughput format. In this report, they printed an array expressing 647 unique genes in duplicate and tested for several well characterized interacting pairs including Jun-Fos and p53-MDM2 [33].
\nA more recent study, Manzano et al. published a work where they applied NAPPA to study protein interactions. In this study, a novel interactor partners were identified for P-selectin and phospholipase A2 and further validated [34].
\nRecently, a novel functional array, designed by Pascal Braun, identified novel cell signaling pathways in
In addition, a further study has just been published where evaluated multi-protein complex in NAPPA format. In this study, four novel tuberculosis-related antigens where identified in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) and also validated with ELISA [36].
\nHere, we have briefly reviewed protein microarray field as suitable platform for multiplex assays in high-throughput format. Thus, the focus was on two main perspectives: (i) Key technological aspects, (ii) Biological Applications.
\nHowever, as we described previously, despite the fundamental advances in protein microarrays, allowing characterization of whole human proteome is still remaining as a challenge. Then, the information provides light on the functions of proteins and genes whose functions are currently unknown.
\nOverall, protein arrays may provide relevant information about the biological function of gene products. Although, it is still necessary to develop and optimize some key aspects of protein microarray in the future, other proteomics approaches could provide complimentary results.
\nWe gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI17/01930 and CB16/12/00400. Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER.
\nThe authors do not declare any conflict of interest.
COPD definition & prevalence. A global public health challenge that can be prevented and treated, COPD is the 4th leading cause of death, estimated to become the 3rd. According to Global Initiative for Chronic Obstructive Lung Disease GOLD 2020, “COPD is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases and influenced by host factors including abnormal lung development” [1].
Prevalence- Worldwide, COPD is underdiagnosed and under-recognized, with a medium of <6% of the adult population described in studies. However, most of the studies define COPD by spirometry, not combining symptoms, limiting prevalence description [1].
Nutritional status evaluation. Body mass index BMI (weight per square height) is not the only criteria which defines nutritional status, moreover other measurements, like bioimpedance will describe better the muscle mass, lean mass and adipose tissue. In COPD, the challenge will be to preserve, muscle mass, in order to support lung function. In scientific research dual energy X ray absorptiometry DXA, magnetic resonance imaging MRI are also used to evaluate body composition, but in daily clinical practice, bioimpedance is widely used.
Importance in COPD. Malnutrition, cachexia, obesity represent important co-morbidities, with impact on COPD evolution, treatment and mortality.
ECRHS is the longest prospective populational study, multicentric that involved 18000 adults along 20 years in 3 phases [5]. Very detailed information have been obtained on forced vital capacity FVC, forced expiratory volume in first second FEV1 as lung function markers. Weight changes were considered as: moderate weight gain 0,25–1 kg/year; stable weight +/− 0,25 kg/year; weight loss −0,25 kg/year. As pulmonary disease diagnosis, asthma was noted. Records about lifestyle were available: smoking status, physical activity, leisure time. Results are summarized below in Table 1.
Baseline- young adulthood | Follow- up for 20 years | FVC, FEV1 at the end of the study | FEV1/FVC at the end of the study |
---|---|---|---|
Normal BMI, overweight and obese | Increase Weight | FVC and FEV1 accelerated decline | Without decline |
Obesity | Decrease Weight | FVC and FEV1 attenuated decline | Without decline |
Underweight as teenagers | Stable weight | FVC and FEV1 attenuated decline | FEV1/FVC ratio in an accelerated decline |
How these data may be interpreted? Weight gain is leading to an accelerated decline of FVC and FEV1, independent of initial weight, normal, overweight or underweight. Clinically, an accelerated decline of pulmonary function was noticed. FEV1/FVC ratio was not altered during weight gain, suggesting the possible restrictive syndrome associated with obesity. For underweight group, surprisingly, FEV1 and FVC decline is attenuated, but the decline of FEV1/FVC ratio is accentuated, concluding that the airflow limitation typical for obstructive pulmonary syndrome may be favorized. Obese people who lost weight during the study period have an attenuated FVC and FEV1 decline suggesting the role played by obesity in the respiratory function and the importance of including obese people in comprehensive lifestyle interventions for restoring a good pulmonary function.
A very large Chinese study included 452259 participants with diagnosed COPD, with a follow-up period of 10.1 years [6]. 10739 hospitalization events and deaths have been reported. The study concluded that underweight, with a BMI < 18,5 represents an increased risk of COPD, adjusted hazard ratio HR 1.78 (95% CI, 1.66–1.89). Abdominal obesity was positively associated with COPD risk, after adjustment for BMI. In conclusion, both, abdominal adiposity measures and BMI should be considered for COPD prevention.
Adipose tissue may be considered a systemic modulator, influencing the response to environmental exposures and should be considered a potential target for future therapeutic interventions. As an endocrine organ, adipose tissue secretes adipokines, which are adipocyte derived factors that could affect airways function. Not only the inflammatory role recognized for leptin, but the anorexigenic role, accelerated metabolism, modulating immune function together with driving ventilatory regulation will influence pulmonary function [7, 8]. Leptin is supposed to increase bronchial hyperreactivity [9] . In contrast, adiponectin is the anti-inflammatory adipokine, exclusively produced by adipocytes. In lean persons their activity is normal, but decrease in obese patients. Hypoxia, adipose tissue inflammation, macrophage infiltration in adipose tissue will induce finally insulin resistance [9].
Many years ago, in 2002 Gruberg used for the first time the term” obesity paradox” to characterize the lower risk of complications and mortality observed for overweight and obese people versus normal weight or underweight patients in coronary heart disease, pulmonary hypertension, heart failure, stroke, hypertension [10]. Not well elucidated, the concept of obesity paradox is still a subject for study. Increased risk of developing obesity is characterizing patients with COPD, since long term treatment with systemic glucocorticoids is administered [11] and usually a decreased physical activity is seen. Loss of free fat mass FFM, accompanied by muscle weakness and exercise capacity decrease is seen in COPD patients, leading to the conclusion that FFM may be a better predictor than BMI. FFM and weight loss will impact prognosis in COPD [12]. Landbo, Jee [13, 14] described a lower mortality risk for COPD patients with higher BMI. Moreover, Cao [15] described for underweight patients higher risk of mortality compared to leaner counterparts. (HR:0.78; 95% CI:0.65–0.94 and HR:0.69; 95% CI: 0.54–0.89). In this context, the importance of cardiorespiratory fitness CRF should not be neglected. Findings from Aerobic Center Longitudinal Study proved that CRF modify the association between adiposity and results on survival. Fogelholm [16] found a lower all cause/cardiovascular CVD mortality risk for individuals with high BMI and improved aerobic capacity, but this protective effect disappear for BMI > 35 kg/m2. In a study concluded by Sabino [17] for 32 patients with COPD, higher FFM and exercise capacity lead to better functional outcomes for overweight and obese patients. Practically, obesity paradox is mainly related to CRF and FFM. The role of physical activity PA is well proved in type 2 diabetes, CVD but not well documented in COPD, suggesting potential future correlations and research PA-obesity paradox-CRF and COPD.
In COPD, considering obesity paradox, a question arise: To treat or not to treat? Best strategy is under research, clinicians dilemma is to recommend weight reduction which will improve cardiac performance but may worsen respiratory performance and increase mortality? Which could be the ideal intervention to loose weight? [18].
A new study published in 2020 may propose new answers [19]. The relationship between exacerbation frequency in COPD should be investigated in detail in order to understand better the obesity paradox [20, 21]. This is an observational, retrospective study performed in Netherlands [19] that included 604 patients with COPD, stratified based on BMI level. Lowest five year survival rate was found for underweight and normal weight patients (35%, 41%, p = NS not significant). Survival increased at 47% (p = 0.028) for overweight group, 51% (p = 0.046%) for moderately obese and 63% for severely obese (p = 0.003) patients, versus normal weight patients. Cox regression analysis showed that the effect was independent by other variables and HR = 0.962 (95% CI 0.940–0.984) p = 0.001. The study demonstrated a significant reduction in the exacerbation frequency that required hospitalization in obese patients. Moreover, a significant decrease by 34–40% of readmissions for obese patients was noticed together with a decreased mortality. In contrast with other studies, were the” protective” effect was lost for BMI > 32 kg/m2, in this study, the group with BMI > 35 kg/m2 was more protected. The fact that cardiovascular comorbidities, atherosclerosis, is causing a higher mortality rate for leaner patients with COPD should be discussed [22]. Fat reserve, offering a protective source of energy along hospitalization in critical illness should be considered, too. This is supported by better survival rate for critically ill patients with a higher BMI [23, 24]. Preserved muscle mass mean a better prognosis influencing stroke volume and cardiac output [25]. Furthermore, lower systemic vascular resistance is described for obese patients. On the other side, underweight patients, in this study, had an increased mortality, attributed to decreased CRF in the context of lower muscle mass, decreased cardiac output and limited energy storage [23, 24]. Underweight is associated with an increased readmission time in this study, in line with previous data about malnourished patients. How the results of this study should be interpreted? They are limited to specific groups of patients suffering from a disease and should not be considered guidelines for preventive measures at populational level, as authors are mentioning. But, best explanation of this paradox will help the specific approach for future interventions. In conclusion, exacerbation frequency reduction in obese patients with COPD may partially explain obesity paradox, but more prospective research is needed.
Malnutrition is represented in COPD with a prevalence of 30–60% [26]. Daily energetic expense with respiratory effort is 36–72 kcal/day, normally, but this value may increase by 10 times in COPD. Malnutrition is produced by increased basal metabolic rate, low nutritional intake, or both. The energy spent may be increased more by infections associated with fever.
The diagnosis of malnutrition will be based on Global Leadership Initiative on Malnutrition GLIM [27] criteria for the Diagnosis of Malnutrition: a consensus report from the Global Clinical Nutrition Community. There are described 3 phenotypic criteria: low BMI, decrease intake or assimilation of food, unintentional weight loss; and 2 etiologic criteria: disease severity, inflammation and muscle mass decrease. For diagnosis, one etiologic and one phenotypic criteria will be mandatory.
Being an unfavorable prognosis in COPD, malnutrition predispose to infections, lead to weight decrease, decrease effort capacity and the strength of respiratory muscles. Moreover infections decrease surfactant production.
Issues to be addressed in COPD: loss of muscle mass is a strong negative prognosis factor, as has been discussed in previous paragraph and should be addressed by a correct medical nutrition therapy that will be detailed later in this chapter.
Larger research focused on wholegrain has been done in relation with cardiovascular disease CVD and cancer [28], but independent benefits have been reported in observational studies on lung function [29, 30] and COPD. Synergic effects of phenolic acids, phytic acid, selenium, vitamin E, essential fatty acids, found in whole grains explain documented benefits on respiratory disease, observed in nonrespiratory diseases, too. Large prospective studies [31] revealed a 40% reduction in the COPD risk after higher fiber intake. Epidemiological data associated fiber intake with lower serum levels of C reactive protein and cytokines (interleukin IL 6, tumoral necrosis factor TNF) and high adiponectine levels, with well-known anti-inflammatory effect. Protective effects are seen mainly for cereal fiber intake in current smokers and ex-smokers, but fruits and vegetable fibers are evidenced, too [31, 32].
The inflammatory/oxidative pathogenetic implications in COPD, as well as nutritional status and the dietary quality in COPD lead to verify the relations between respiratory effects of antioxidants and anti-inflammatory dietary components. In 2 recent Swedish populational studies, beneficial role of high consumption of fruits and vegetables on long term was reflected in a decreased incidence of COPD, 35% decreased risk in men (p < 0,0001) and 37% lower risk for women (p < 0,0001) consecutive high consumption of fruits (boths) and vegetables (men). This benefit was mainly obvious in smokers [33, 34]. In conclusion fresh, hard fruits and vegetables provide benefits on lung function decline, COPD symptoms, COPD incidence and mortality. Specific, the protective effect in the men cohort was limited to current smokers or ex-smokers, explained probably by increased antioxidative stress level in smoking. Individual food items observed: apples, pears, peppers, green leafy vegetables [33].
Limited evidence is reported about any benefit of vitamin D supplementation in COPD progression and immune responses. A conclusion can be drawn, for patients with baseline low level of (OH) D < 25 nmol/L supplementation is beneficial in preventing COPD exacerbations [35]. There are described genetic mutations of vit D binding protein associated with decreased vit D levels linked with a higher risk of COPD [36]. Conflicting results are reported with vit D supplementation but in conclusion they pointed out a benefit for patients with low baseline levels of (OH) D < 25 nmol/L, the active metabolite of vitamin D [37]. The antioxidative effect of vitamin E is revealing promising options for lung function decline associated with age. Well recognized action for vitamin C, which protects lung tissue, focusing on lung function maintenance mediated by vitamin C may lead to a greater success in exploring potential targets in preventing pulmonary diseases [38].
Intake of calcium, phosphorus, potassium, iron and selenium are positively associated with lung function measures (measured by FEV1) based on a case control study published in Japan. 35% reduction of COPD risk is inversely correlated with Calcium intake [39]. An independent positive correlation is found between FEV1 and selenium, calcium, iron and chloride but inverse correlation with sodium and potassium in the general population [40]. Cooper and selenium serum levels are also related to higher lung function in other cross-sectional studies [41]. Through its protective effect against bronchoconstriction and inflammation, Magnesium may play a beneficial role in pulmonary function [42]. Further studies are warranted to prove protective effects of some minerals, explained mainly by antioxidant and anti-inflammatory properties.
Higher intake of ω3-PUFA is related to lower levels of cytokine TNF (OR = 0.46, p = 0.049) in stable patients with COPD. The same study mentioned the association between a high intake of ω 6-PUFA with high inflammatory markers, for example C reactive protein CRP, interleukin 6, IL6. (OR = 1.96 for IL-6, p = 0.034; for CRP OR = 1.95, p = 0.039) [43]. Lower FEV1 after higher consumption of ω6-PUFA was evidenced in a large population based cross sectional study, mainly in smokers, with a higher risk of COPD but without relation to ω3-PUFA [44]. Potential fish benefits in the diet might be obvious within the whole diet, as a recent analysis of two large cohorts is suggesting [45]. 4 servings of fish/week were associated with lower risk of newly diagnosed COPD in 2 large US cohorts. A healthy diet including fish and vegetable sources of ω3-PUFA may be beneficial for COPD, as fish intake could reduce the risk of COPD when plant sources of ω3-PUFA intake is high.
A cross sectional analysis of NHNES [46] associated independently an obstructive pattern in spirometry with increased intake of cured meat but also with newly diagnosed COPD patients, independently of Western dietary pattern or other associations [46, 47]. A more recent large populational study from Sweden confirmed the detrimental effect of processed red meat [48, 49] but not unprocessed. Another reference showed an increased risk of readmission from COPD associated with cured meat intake. A meta-analysis, recently summarized results indicating that higher consumption of red processed meat (more than 75-785 g/week) is leading to a 40% increased risk of COPD [50, 51].
In COPD pathogenesis, pollution, genetics, smoking, aging, play a role in developing inflammation, oxidative stress, mucus hypersecretion, antioxidant depletion, airway remodeling [28] . But lung function is influenced by dietary factors, too. Detrimental role for lung function of Western type diet, characterized by high energy dense food, red and processed food, added sugar, high salt intake, preservatives, low antioxidants, high glycemic index and saturated fats is already proven. By contrast, fruits, vegetables, whole grains, alcohol, wine, legumes, nuts, coffee, fish, high antioxidants, low glycemic index and unsaturated fats, as part of a mediterranean healthy pattern are a support of a healthy lung function. As dietary patterns, is clearly proved the detrimental role of Western model and the protective role of Mediterranean model in COPD.
A special pyramid was designed for COPD patients, represented below, in Figure 1, adapted after International Journal of COPD, 2020 [52].
Food pyramid for subjects with COPD.
Daily energy has to be adapted to activities and requirements calculated by bioimpedance and calorimetry in order to maintain BMI below 30–32 kg/m2. (special situation in malnutrition is detailed separately). Recommended macronutrients proportion is: 15–25% proteins, 30–45% fats, 40–55% carbohydrates. It has to be underlined that the % of macronutrients is important to maintain (respiratory quotient)RQ, the marker for respiratory tolerance of the pattern recommended. Respiratory quotient, defined as CO2 volume expired/O2 volume consumed is the respiratory parameter that indicates food mix metabolized. RQ is 1 for carbohydrates, 0.85 in mixed diets, 0,82 for proteins and 0.7 for fat. The macronutrient percentage is important, correct diet, but not overconsumption will be critical for COPD patients which have compromised ability for gas exchanges, because excess calories produce CO2 that must be expired and will influence the respiratory process [26]. Considering drug-food interactions, special attention should be considered for salt intake during oral corticosteroid treatment, that should be minimized. Meanwhile, due to increased risk for metabolic disorders, especially high glycaemia, sugar intake should be limited [26].
Muscle mass decrease is a risk factor for mortality from COPD and muscle mass maintenance is important. Considering these, the recommended daily protein intake is 1,2–1,5 g/kgb/day, combined with physical exercises, much more compared to general population recommendations of 0.75–1 g/kgb/day [53]. General recommendations, specified in the 2019 obesity guidelines [54] should be emphasized: decreasing food energetic density, avoid skipping meals, but also snacking, eating just as response to hunger sensations and stop eating when satiety appears, eating slowly and mindfully, as an assumed responsibility, not as a restriction.
the objective is to address hypermetabolism in order to prevent weight decrease and lean mass decrease. Practically lean mass/muscular mass maintenance is the key for a good prognosis in COPD [26]. From clinician perspective, MNT should address appetite decrease and improper food intake. Main recommendations are: small meals, frequent, nutritional dense. The main meal should be at the time when the energetic level is the highest. It is recommended to rest before meal. The proper caloric intake will be adjusted in order to maintain a BMI of 20–24 kg/m2. Availability of food which request minimum time to be prepared, eventually pre-prepared is important. To limit alcohol intake <2 portions/day, 30 g is mandatory.
All these nutritional recommendations should be integrated in a healthy lifestyle. Mandatory tobacco cessation, gradual increase in physical activity, according to cardiorespiratory fitness score, optimal sleep and mindfulness, seen as a harmony between mind, body, thoughts and feelings will be beneficial for COPD patients. Despite a great interest in managing COPD, there is a gap in recommendations for physical activity (PA), the most commonly prescribed PA is: walking, cycling, strength training and nonspecific aerobic training. Physical activity PA should be part of lifestyle, may be performed in groups, social or independently. People with COPD should be active until breathless or as per their capacity. Recommended PA durations are ranging from 20 to 45 min/day, depending on guideline. For severe patients, to add short intervals rather than a continuous activity is mentioned. No specific guidelines are mentioning sedentary behaviors. Despite the fact that no specific sleep recommendations are in COPD guidelines, we encourage a referral to a sleep specialist [55].
Post COVID 19 pulmonary rehabilitation measures, which start in the hospital for moderate cases, will improve symptoms like dyspnea, anxiety, depression and should continue as part of a healthy lifestyle after recovery, for future. A healthy lifestyle, normalizing body weight by adopting a healthy model adapted to caloric and nutritive requirements daily physical activity and an optimal sleep, mindfulness, will remain key principles for COPD patients after SARS-COV2 infection.
New concept of cardiometabolic disease reflects in a more appropriate way the role of adipose tissue in all comorbidities developed in obesity. Lung function decline associated with obesity, as it is revealed by important studies may be an interesting relation to be considered in COPD obese patients. Moreover, malnutrition, with the worst prognosis on COPD development will influence patients management. The importance of a healthy dietary pattern in COPD, designed in the new COPD pyramid are suggesting the strong correlation between foods, nutrients in order to achieve best therapeutical results. Medical nutrition therapy in COPD, based on Mediterranean model, with a high % of proteins, integrated in a healthy lifestyle should be part of COPD management. Nutritional status play an important role in future COPD prognosis and a multidisciplinary team with pneumologist, nutritionist and kinetotherapist should cooperate in order to achieve best long term outcomes.
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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 15th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:286,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/428875",hash:"",query:{},params:{id:"428875"},fullPath:"/profiles/428875",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()