Chromatographic and spectrometric methodologies used recently in lipoproteomic analysis.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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The emerging high-throughput omics such as genomics, transcriptomics, proteomics, and metabolomics have been used in the search of new biomarkers in several diseases. Proteomic analyses or metabolomics and lipidomics as well as complementary technologies such as mass spectrometry (MS) (i.e., LC-MS-MS and MALDI-TOF/TOF), nuclear magnetic resonance spectroscopy, and other omics technologies, are being widely used in the search of new sources of markers, candidates for vaccine, and alteration of expression patterns in response to environmental changes and signaling pathways in different diseases. The search for proteins in the dynamic system of a proteome requires various proteomics approaches and the use of proteomics is crucial for the early disease diagnosis, prognosis, and to monitor the disease development. The proteomics is essential for the understanding of complex biochemical processes, and the high-throughput proteomics increases the depth of proteome coverage.
Lipoproteins are macromolecular complex particles of lipids and proteins, which are related to the extracellular transport of lipids in many organisms [1]. Besides, lipoproteins have been also implicated as important host defense mediators and in the initiation of immune responses [2, 3, 4]. Lipid content has long been recognized as a critical factor in lipoprotein metabolism that acts as an important determinant of human health [5]. However, in last years, apolipoproteins and lipoprotein-associated proteins have been taken on relevance regarding lipoprotein metabolism since they serve as a frame for their assembly, maintain their structure, and interact with the membrane receptors and enzymes. Therefore, these proteins could be crucial in the identification of biomarkers related to diseases due to the fact that they are being studied under a global approach, denominated lipoproteome [6, 7].
Lipoproteins are complex protein particles of an amphipathic nature, structurally are formed by an outer layer of phospholipids, free cholesterol, and apolipoproteins, and inside contain a nucleus of cholesterol esters and triglycerides [8]. When the lipoprotein complex is formed, the orientation of the hydrophilic proportions is toward the outside and the lipophilic proportions toward the interior; this structural characteristic allows the complex to have the ability to emulsify fats in extracellular fluids [8]. Based on their density defined by the protein to lipids ratios, lipoproteins are grouped into six classes: chylomicrons, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipoprotein (a) [Lp (a)] [8, 9].
Triglycerides, derived from dietary fat absorption by the small intestine, are carried by the chylomicrons into blood. After triglyceride digestion to free fatty acids (FFA) by lipases in the peripheral tissues, the size of these particles is reduced, which leads to the formation of chylomicron remnants. These latter are cleared by liver uptake via LDL receptor-related protein (LRP). To synthesize VLDL, newly synthesized triglyceride and cholesterol by the liver are incorporated into chylomicron remnants [8, 10]. These large triglyceride-rich VLDLs are released to the circulation and travel to peripheral tissues, where the lipase digestion of triglycerides occurs resulting in the IDL formation (VLDL remnants). These IDL particles can be either cleared from the circulation by the liver in a similar manner to that described for chylomicrons remnants or can be digested by hepatic lipase to generate cholesterol-rich LDL particles, which is taken up by the peripheral tissues via LDL receptor to supply their cholesterol requirements [10].
The HDL lipoproteins have the highest relative density as compared to other lipoproteins despite being the smallest in size and heterogeneous in terms of composition. These HDL particles play an important role in the transport of reverse cholesterol as a carrier in the movement of cholesterol from peripheral tissues back into the liver [11]. The liver and intestine, practically in response to the lipolysis of triglyceride-rich lipoproteins, synthesize and secrete the nascent discoid HDLs that consist primarily of phospholipids and free cholesterol. Then, these particles reach the plasma where additional exchangeable apolipoproteins are picked up and excess free cholesterol is removed from both extrahepatic cells and other circulating lipoproteins, forming mature spherical HDL particles. Finally, these cholesterol-rich HDL particles can be delivered back to the liver [10, 12].
The protein cargo related to lipoproteins consists of apolipoproteins and lipoprotein-associated proteins. These proteins play key roles in lipoprotein metabolism such as structural component, enzyme interaction, and receptors recognition, among other functions [7]. Changes in the quantity and type of these proteins could be involved in the outcome of diseases related to lipid metabolism. Therefore, the proteomic analysis of lipoproteins is an important notion for the present revision.
The apolipoproteins can be classified as integral or peripheral, either they act as constituent components of the plasma membrane of the lipoproteins or they bind to the membrane and can be exchanged between one complex and another, respectively. Apolipoproteins are distributed throughout all lipoproteins and subfractions, with the proportion of them varying in each family. These variations in the amount of proteins present in the lipoprotein families in their membrane gives them their capacity to interact with different tissues [7, 10].
Within the apolipoprotein A (ApoA) group is the apolipoprotein A-I (ApoA-I), the main protein component of HDL, which plays multiple roles in the transport of cholesterol, in addition to having been linked to the regulation of some functions of the inflammatory and immune response [13]. ApoA-II, also found in HDL, acts as an enzymatic inhibitor of lipoproteins and liver lipases. The apolipoproteins are capable of binding to each other to modify the interaction of the lipoprotein complex, as is the case with apoA-I and apoA-II in LDL [10].
ApoA-IV is mainly synthesized in the small intestine where it is attached by enterocytes to the chylomicrons and secreted during a high-fat meal intake. ApoA-IV is associated with HDL and chylomicron remnants in circulation, but a significant portion is free [14]. On the other hand, ApoA-V participates in the regulation of triglyceride levels in plasma [15]. ApoA-V is expressed only in the liver and circulates at low concentrations. Despite this, apoA-V can be recovered in association with plasma lipoproteins [16].
The apolipoprotein B (ApoB), the main protein component of chylomicrons, LDL, VLDL, IDL, and Lp (a), is encoded by a single gene that gives rises to two isoforms: ApoB-48 and ApoB-100. ApoB-48 is produced exclusively in the intestine and is the major structural protein of chylomicrons and chylomicron remnants. ApoB-100 is expressed in the liver and is found only in VLDL, IDL, LDL, and Lp (a). ApoB-containing lipoproteins are characterized by a spherical shape and contain one single apoB-48 or apoB-100 molecule per lipoprotein [17].
Apolipoprotein C (ApoC) works as an inhibitor of certain processes and modulators of catabolism. ApoC is mainly synthesized in the liver and easily transferred between lipoprotein particles and therefore are found associated with chylomicrons, VLDL, and HDL [10]. ApoC-I is responsible for inhibiting the binding of lipoprotein to its receptor as well as the function of the esterified cholesterol transfer protein (CETP). ApoC-II is an essential cofactor of the lipoprotein lipase involved in triglyceride hydrolysis. Both apoC-III and apoC-IV inhibit triglyceride hydrolysis. In addition, apoC-III decreases the clearance of VLDL [10, 18].
Several tissues synthesize apolipoprotein E (ApoE), an exchangeable apolipoprotein associated with chylomicrons, chylomicron remnants, VLDL, IDL, and a subgroup of HDL particles, but the liver and intestine are the principal producers of circulating ApoE [10]. ApoE functions as a lipoprotein ligator with hepatocytes (clearance of apoE-containing lipoproteins) and peripheral cells related to the LDL receptor. ApoCs and apoEs are interchangeable between complexes during the conversion of VLDL to LDL. ApoEs may function as a lecithin-cholesterol acyltransferase (LCAT) activator and influence the activity of hepatic lipase and CETP [19, 20].
Proteins belonging to the lipocalins family such as apoD, apoM, the orosomucoid protein, and retinol-binding protein (RBP) interact with the surface receptors of the cells, intervening in the formation of macromolecular complexes. It has been described that apoD binds to apoA-II and apoB-100 by means of disulfide bridges; it is associated with LCAT, so it is involved in the transport of lipids in the blood system. ApoJ is involved in a wide variety of processes, acting as a chaperone protein and its main role is the inhibition of lipid transfer and is related to cell death. There are apoproteins such as apoF whose function is unknown; however, there is a theory of their role in abnormal lipid composition inhibiting CETP in the small and dense LDL particles (sdLDL) [21, 22].
In addition to apolipoproteins, lipoproteins require other proteins with specific activities to interact with the environment, which are denominated as lipoprotein-associated proteins. Between these proteins are included phospholipase A2, whose activity indicates the presence of sdLDL in plasma [23]. Serum amyloid A protein (SAA) is associated with several lipoproteins, especially in LDL [24]. Some proteins such as albumin and prenyl cysteine oxidase (PCYOX1) are responsible for protecting against oxidation by lipoproteins such as LDL and splitting the thioether bond of the prenyl cysteine generating H2O2, respectively. Also, proteomic studies have identified the apoL-I, PON1, and PAF-AH in small amounts linked to the complexes [25, 26].
The function of many of the proteins that interact with lipoproteins is still unknown. The proteomic analyses have shown that the lipoprotein-associated proteins are involved in cardiovascular risk, immune system, inflammatory processes, among others [7, 26]. However, there is no guide for the analysis of lipoproteins at the proteomic level basically because it depends on the biological question to be investigated, and this determines the approach and the methods or tools to be used as well as the technological platform to perform it.
Before describing the methodologies used for lipoproteomic studies, it is important to mention some general characteristics of lipoprotein-associated proteins and the importance of the research question to establish a good methodological flow chart to address this question. We will start by mentioning that must first consider the lipoprotein obtention by using methods for separation, concentration, and protein stability due to the heterogeneity of these particles.
Diverse chromatographic techniques—prior to proteomic techniques—have been used for the separation of plasma lipoproteins as well as the protein content, such as capillary electrophoresis, size exclusion, cation exchange, gel filtration, fast protein liquid, among other chromatographic techniques [7, 27, 28, 29, 30, 31, 32].
The two-dimensional electrophoresis (2-DE) is one of the most usual methods that have been applied to separate the protein cargo related to lipoproteins. Although usually, the first-dimensional separation applied for the proteins in the 2-DE is on base of their charge (isoelectrofocusing), some lipoproteomic analyses have substituted this step by either one of the abovementioned methods to separate lipoproteins or electrophoresis on native gels, followed by SDS-PAGE, which could be denominated as gel-based lipoproteomics [27, 33, 34, 35].
Lipoprotein-associated proteins are not easy to study by proteomic methods, mainly the embedded in the lipoprotein membranes. These latter have rigid transmembrane domains that contain α-helices or β-barrels, which stabilize the protein by strong secondary structural characteristics and these regions can resist proteolytic digestion [6, 36]. Thus, the protein identification for lipoproteomes has been mainly performed by two methods: mass spectrometry and resonance magnetic nuclear.
Modern mass spectrometry (MS) techniques have allowed for thorough characterizations of the lipoproteins [37]. However, different experimental conditions have been reported to avoid contamination of the biological samples as well as selective and optimized methods to detect lipoproteins, usually liquid-phase separation techniques, prior to spectrometric techniques [36, 37]. Thus, different spectrometric experimentation conditions have been reported for the study of lipoproteins and apoproteins, respectively (Table 1).
Pre-analysis | Chromatography | Mass spectrometry | Analysis | Post-analysis | ||
---|---|---|---|---|---|---|
Source | Methods | chromatographic technique = Instrumentation (method) | Mass analyzer = Instrumentation (method) | Database search | Number of lipoproteins and apoproteins | References |
Mice C57BL/6 J: plasma | Gel filtration/size exclusion chromatography, phospholipid-containing particles using CSH | LC-ESI = C18 reverse phase column (GRACE; 150 × 0.500 mm) | Quadrupole/TOF = 4800 scans, mass range: 300–1800 | Swiss-Prot protein knowledge base for | VLDL/LDL: 32, HDL: 104; lipid poor lipoproteins: 55 | [37] |
Human serum (HDL) | Trypsin, delipidation, gold nanoparticles and LDI-MS, EDX, SPE, FT-IR | MALDI-MS = nr | Swiss-Prot, Lipidmaps database | HDL (delipidation): 10 (prior), 6 (after). HDL (anion exchangers): 23 | [38] | |
Mice C57BL/6 J: apoA-I KO and apoA-II KO, apoA-I KO and WT: plasma | Particles of CSH. Plasma separation by size exclusion chromatography | LC-ESI = column (C18 reverse phase (150 × 0.500 mm)) | Quadrupole/TOF = MS/MS. tolerance were set to ±35 PPM, and up to 3 missed tryptic cleavage sites were allowed | UniProtKB/Swiss-Prot Protein Knowledgebase, Peptide Prophet algorithm | HDL: WT:25 vs. ApoA-I KO: 21; ApoA-II KO: 11 vs. WT: 14; and ApoA-IV: 6 KO vs. WT: 7 | [28] |
17 Subjects (exposure to organic pollutants): plasma (HDL) | Ultracentrifugation (290,000 g, 15°C, 4 h) | nLC: Column C18, ESI | Linear ion trap-Orbitrap: CID. ms/ms: 0.6 Da | MaxQuant v1.5.0, human Uniprot/Swiss-prot database | LCMS permit identified the pathway of interaction between HDL-proteins | [39] |
34 Men (2 dietary: weight loss/high car): plasma (LDL, ApoC-III) | ELISA assay | MALDI-TOF: 500 laser shots mass spectra | Detection and concentrations values of 12 apoC-III glycoforms | [40] | ||
Mice (female, LDLr−/−, 8 week old): plasma (VLDL, LDL, HDL) | FPLC, ELISA assay | LC | Orbitrap: mass tolerance: 0.8 Da | Swiss-Prot database | HDL: 91 LDL: 49 VLDL: 39 | [41] |
1000 Children (6–8 years, Nepal rural zone): plasma | Cation exchange chromatography | LC | Orbitrap | Refseq 40 database | Apo-AI, Apo-AII, Apo-CIII | [42] |
458 Children (6–11 years, exposure to environmental tobacco smoke): serum (HDL, LDL) | SPE-HPLC-TIS-MS/MS | LC detected various polyfluoroalkyl substances in serum A negative association PFOS and non-HDL | [43] | |||
57 Males (exposed to arsenicum): plasma, urinary (LDL, HDL, Lp(a), Apo-A1, Apo-B) | Centrifuged at 3500 rpm for 10 min | ICP-MS: extraction voltage −100 V, Rf power 1400 W, focus voltage 12 V, and nebulizer gas flow rate (using a Burgener Miramist nebulizer) 0.83 L/min. Dwell times were 50 ms for 75As and 10 ms for internal standard (72 Ge) | ICP-MS: Potential risk of the arsenic on lipoproteins and apolipoproteins | [44] | ||
Human healthy, normolipidemic males: plasma (LDL) | Gel filtration chromatography, ultracentrifugation. | nLC: column (IntePepMap 100, C18, particle size 3 um), flow rate = 300 nL/min ESI: 2.5 kV, 150°C | Triple quadrupole TOF: mass tolerance: 50 mDa, 350–1800 | UniProtKB/Swiss-Prot Protein Knowledgebase, Peptide Prophet algorithm | LC-MS permit the abundance protein as well as antioxidant activity | [30] |
110 Samples (purchased) | Phospholipids: UHPLC: column (2.1 × 100 mm, 1.7 uM particle), flow rate: 0.7 mL/min, ESI | Qtrap: MRM scanning, negative and positive mode | Multiquant software functions, JMP (SAS Institute) | LC-MS analysis of serum/lipoproteins | [45] | |
23 Healthy volunteers: serum | Gel filtration chromatography, sequential ultracentrifugation, immunoassay | UPLC: column (UPLCR BEH C8), floe rate: 450 uL/min., 60°C, autosampler: 4°C ESI | Triple-quadrupole: positive ion mode. Quantification of plasmalogens: Capillary voltage: 3500 V, source temperature 80°C, desolvation: 400°C, cone voltage: 35 V. CE: 20–32 eV | LCMS: distribution of each molecular species in plasmalogen and choline plasmalogen | [46] | |
Healthy volunteers: plasma (VLDL, LDL, HDL) | Ultracentrifugation, SDS-PAGE, size exclusion chromatography, circular dichroism, spectroscopy, spectropolarimeter | MALDI-TOF: 337 nm nitrogen laser, positive ion: 20 kV | Identification of apolipoproteins released from VLDL by mass spectrometry | [47] | ||
20 Patients with lipoproteins (a) (18–70 years): plasma (LDL, HDL) | Ultracentrifugation, ELISA | LC: solid-phase extraction | Triple Quadrupole-linear ion tramp: SRM. (energy collision: 34 V, Q1: 786–788; Q2: 1069–1072 | LC-MS system: concentrations of lipid, lipoprotein and apolipoprotein | [48] | |
Healthy donors (nonlipidemic, 24–65 years, purchased samples): plasma (HDL, LDL) | Ultracentrifugation (330,000 g, 6 h), SDS-PAGE and Western blotting, Negative stain electron microscopy | UPLC: column (Kinetex EVOC18), ESI | Triple-quadrupole: lipid species were analyzed by selected reaction monitoring (from 141 to 369 | Extraction and ionization efficacy by calculating analyte/ISTD ratios (AU) and expressed as AU/mg protein | LCS permit the separation of a mixture in HDL protein | [49] |
12 Healthy male (36–67 years): plasma (HDL, LDL) | Ultracentrifugation (40,000 rpm, 44 h, 15°C), fractioned, apoA-I was detected by Western blotting, internal standars | HILIC-UHPLC-FLD: Glycan chromatography column, 150 × 2.1 mm i.d., 1.7 μm BEH particles, flow rate of 0.56 mL/min | MALDI-TOF-MS: 25 kV, acceleration voltage: 140 ns extraction delay, mass window: 1000–5000 | LDL: 18 HDL: 22 N-glycome of human plasma lipoproteins | [50] | |
16 Healthy adults: plasma (HDL, apoA-I, apoB) | Ultracentrifugation. PRM analysis (shotgun proteomics experiments). | UPLC: flow rate: 0.6 uL, column (Xbridge BEH C18) ESI | Orbitrap: PRM mode, isolation window: 2 Th, HCD: 27%, orbitrap analyzer: 15,000 resolution, AGC: 5 × 104, maximum ion time 30 ms | PeptideAtlas mass spectral database | Meal macronutrient content HDL composition in the postprandial state | [51] |
47 Volunteers: serum (HDL, non-HDL). | Anti-apoAI magnetic nanoparticles (10 mg) and serum (5 μl) were mixed FTIR, X-ray diffraction | ID/LC/MS system: LC: column (waters symmetry C18), flow rate: 0.3 mL/min. APCI: corona current: 5 uA, source temperature: 450°C | API 4000 tandem mass spectrometer (triple-quadrupole): Collision energy: 26 eV, collision exit potential: 6 V | ID/LC-MS permit the monitoring serum in clinical settings to dyslipidemia and atherosclerosis | [52] |
Chromatographic and spectrometric methodologies used recently in lipoproteomic analysis.
SRM: selected reaction monitoring. HPLC: high performance liquid chromatography. HILIC-UHPLC-FLD: hydrophilic-interaction ultra-high-performance liquid chromatography with fluorescence detection. LC: liquid Chromatography. UPLC: ultra-performance liquid chromatography. MALDI: matrix-assisted laser desorption/ionization. TOF: time of flight. Qtrap or LTQ linear trap: triple quadrupole-linear ion trap. CE: collision energy. MS/MS: tandem mass spectrometry. PRM: parallel reaction monitoring. AGC: automatic gain control. ID/LC/MS: isotope dilution liquid chromatography mass spectrometry. ESI: electrospray. nESI: nano-electrospray. FPLC: fast protein liquid chromatography. MRM: multiple reaction monitoring. HILIC: silica-based and solid-core reverse phase after hydrophilic interaction. ICP-MS: Inductively coupled plasma-mass spectrometer. SPE: solid phase extraction. SPE-HPLC-TIS-MS/MS: solid phase extraction coupled to high performance liquid chromatography-turbo ion spray ionization-tandem mass spectrometry. SEC-FPLC: size exclusion chromatography by fast protein liquid chromatography. APCI: atmospheric pressure chemical ionization. CID: collision-induced dissociation. LDI-MS: laser desorption/ionization mass spectrometry, EDX: dispersive X-Ray Spectroscopy. CSH: calcium silica hydrate. WT: wild-type. KO: knockout. FTIR: Fourier transformation infrared.
There are several challenges in the lipoproteomic analyses performed with the most advanced mass spectrometry methods. Some of them are the abundance of proteins from the biological source and the lipoprotein(s) purification steps, which conditioned the protein content and constitution. However, if this obstacle can be overcome, the mass spectrometry analysis has been demonstrated to be a useful tool to identify a diverse array of proteins related to lipoproteins, avoiding aberrant integration of unexpected proteins by reducing the suppression of ionization at high peptide resolution [53].
On the other hand, the nuclear magnetic resonance (NMR) technique permit, besides protein identification, can provide information of the lipoproteins at both molecule and atomic levels under physiological or ‘near-physiological’ conditions. The signal most used to quantify lipoproteins is the methyl signal because give a specific response in the lipids that travel inside the lipoproteins [54, 55]. In this way, proton spectroscopy has been the most used nuclear magnetic resonance technique to quantify lipoproteins, but it is not the only one as will be seen later (Table 2).
Pre-analysis | | Spectroscopy experiment NMR type | Post-analysis | References | |
---|---|---|---|---|
Source | isolation method | |||
133 Caucasian participants (T2DM, >18 years): serum (VLDL, LDL, and HDL) | 1H: FT, 400 MHz | Determinate the lipoprotein subtraction characteristics | [56] | |
98 people (T2DM/ nor T2DM): plasma (GlycA vs. Lp-PLA2) | Centrifugation (1400 g, 15 min) | 1H: 400 MHz, 47°C, CaEDTA resonance at 2.519 ppm was used as the internal chemical | GlycA is correlated with LP-PLA2 in plasma (person without T2DM/MetS) | [57] |
23 patients with primary aldosteronism: plasma (HDL, VLDL, LDL, ApoB, and ApoA-I) | Immunoturbidimetric assay | 1H: 400 MHz, 47°C. (LipoProfile-3 algorithm) | Circulating LDL may contribute to adrenal steroidogenesis in humans | [58] |
115 nondiabetic women (35–55 years, mediterranean diet, physical exercise, 2 years): plasma (HDL. LDL) | 1H | Lipoprotein size, particle and subclass concentrations | [54] | |
Human serum (purchased) spiked into phlebotomy tubes (LDL, HDL) | Centrifugation (3000 g, 5 min, 4 h) | 1H: 600 MHz | Lipoprotein subclass analysis standardized by tube type and tube size to prevent risk of analytical interference. | [59] |
Patients with HFrEF (782), HFpEF (1004), and no HF (4742): plasma (HDL) | NMR LipoProfile-3 algorithm | Quantify concentrations of HDL. Phenotyped cohorts of HFrEF, HFpEF, and patients without HF | [60] | |
4897 subjects: plasma (LDL) | 1H: 400 MHz | Differentiate in the size of particle in LDL profile | [61] | |
309 patients (MACE): plasma (HDL, LDL, and VLDL). Control:902 | 1H | Neither baseline HDL nor the change in HDL on treatment with dalcetrapib or placebo was associated with risk of MACE after ACS | [62] | |
Normal volunteer: plasma (HDL, LDL, andVLDL) | Sequential ultracentrifuge | 1H, 13C, 15N: 600.55 MHz, 47°C, different pressures | Show the spatial arrangement, phase behavior and molecular dynamics in the particle core | [55] |
3446 participants (HDL, LDL, and VLDL) | 1H: LipoProfile-3 algorithm | Association between FGF21 and NAFLD | [63] |
NMR methodology applied recently in lipoprotein-based analyses.
MHz: megahertz (106). MetS or MS: metabolic syndrome. T2DM: type 2 Diabetes mellitus. FT: Fourier transforms. CaEDTA: EDTA mono calcium. GlycA: glycoprotein acetylation. Lp-PLA2: lipoprotein-associated phospholipase A2. HFrEF: reduced ejection fractions. HFpEF: preserved ejection fraction. HF: heart failure. MACE: major adverse cardiovascular events. FGF21: fibroplast growth factor21. NAFLD: nonalcoholic fatty liver disease.
Furthermore, not only 1H NMR has been the technique used for the study of lipoproteomics but also the two-dimensional NMR techniques have been used. The two-dimensional heteronuclear 13C▬1H chemical-shift made it possible to analyze macromolecular complexes like HDL, but with a limited resolution in reduced peaks above 50 ppm and the limited resolution in the 29–33 ppm region, inclusive with artifacts that would later be discarded by the spectra of one dimension (1H and 13C) [64].
In addition, the material to be used for the spectroscopic analysis should be the optimal one to avoid contamination, as in the case of a tube used for the collection of biological material and used in clinical research, which should be specifically for the analysis of lipoproteins [59].
Also, the experimental conditions do not always favor the use of NMR for the analysis of lipoproteins. Thus, mass spectrometry permits the particle identification via LC-MS system in contrast to NMR spectroscopy, which failed. Due to that, the NMR spectroscopy makes HDL particle quantification only in a physiological setting: full serum or plasma but not in HDL-containing suspensions [49]. Therefore, the technician must consider the biological and technical variables for an assertive lipoproteomic analysis.
The lipoproteomic analyses have been focused on understanding the functional mechanisms underlying apolipoproteins and lipoprotein-associated proteins that can be used to develop new diagnostic and/or prognostic biomarkers for many lipoproteins’ metabolism-related illness.
The HDL lipoprotein fraction has been the most studied according to lipoproteomic relationships with different diseases. Among the HDL-associated proteins, ApoC-III levels have been seen increased in the patients with either a lupus nephritis (lupus erythematosus) or with a cerebral lacunar infarction, which could be related with a reduced anti-inflammatory activity of HDL particles [65, 66].
However, HDL-carried ApoC-III has been more implicated in cardiovascular disease (CVD) risk. One of the first evaluations was performed with coronary artery disease patients, which exhibit increased levels of ApoC-III [67]. Recently, in a cohort study, it was demonstrated that HDL-carried ApoC-III is related to a higher risk for coronary heart disease [68].
In addition to ApoC-III and ApoC-II, other HDL-associated apolipoproteins, were proposed as biomarkers for CVD risk in patients with chronic hemodialysis [69]. The ApoC-III/ApoC-II/ApoE levels in VLDL lipoproteins, independent of HDL, were associated with incident CVD, which supports the concept of targeting triacylglycerol-rich lipoproteins to reduce the CVD risk [70].
Other HDL-associated apolipoproteins have been associated with cardiac pathologies. For example, ApoA-I, ApoA-IV, ApoE, and ApoL1 levels have been seen enriched in HDL3 fraction from patients with acute coronary syndrome (ACV), with a concomitant reduction of these apolipoproteins in the HDL2 fraction [71]. Furthermore, ApoC-I was significantly decreased in the HDL particles of coronary heart disease (CAD) patients in comparison to normal individuals [72]. The existence of CAD has recently been correlated with an HDL apolipoproteomic score, independent of circulating ApoA-I and ApoB rates and other typical cardiovascular risk factors [73].
Regarding HDL-associated proteins, many of them have been related to heart illness. For example, serotransferrin, haptoglobin, hemopexin, complement factor B, ras-related protein Rab-7b, and paraoxonase-3 (PON3) levels have been seen reduced in HDL from patients with some cardiac pathology. Meanwhile, PON1, alpha-1B-glycoprotein, vitamin D-binding protein, alpha-1-antitrypsin (A1AT), acid ceramidase, serum amyloid A and P proteins, sphingosine-1-phosphate, filamin A, and pulmonary surfactant-associated protein B are increased in HDL fractions from patients with cardiometabolic disorders [69, 71, 72, 74, 75].
Diabetes is, perhaps, the major controllable risk factor for CVD. In particular, related to the HDL fraction, ApoA-I, ApoA-II, ApoA-IV, ApoE, ApoJ, as well as PON1, transthyretin, complement C3, and vitamin D-binding protein have shown changes in patients with type 2 diabetes (T2D) [76, 77]. In contrast, individuals with type 1 diabetes (T1D) had proteomic alterations of their HDL particles. For example, the complement factor H-related protein 2 was elevated, independent of glucose control, in T1D patients in comparison to healthy controls. Also, the optimal glucose control corrected the elevated levels of the alpha-1-beta glycoprotein and inter alpha trypsin inhibitor 4. Furthermore, the HDL particles in T1DM individuals, independent of glucose control, exhibit a higher abundance of irreversible post-translational modifications of HDL-associated apolipoproteins [78, 79].
Also, in psoriatic patients, the levels of HDL-associated ApoA-I exhibit a significant reduction, whereas levels of apoA-II, serum amyloid A, C3, and A1AT, among other proteins were increased [80]. Besides C3 and C9, complement factor B, as well as ApoJ, fibrinogen, haptoglobin, and serum amyloid A have been also increased in HDL fraction from patients with rheumatoid arthritis [81]. Taken together, these results suggest that HDL-associated proteins could be involved in anti-inflammatory properties in chronic illness.
Concerning other diseases, the proteome of HDL particles has been used to identify protein markers. In nonalcoholic fatty liver disease, including individuals with nonalcoholic steatohepatitis, changes in the abundance of HDL-associated proteins such as antithrombin III and plasminogen have been identified [82]. Although not directly to HDL particles, proteomic analysis of some HDL-related apolipoproteins has been associated with viral diseases. For example, a change in the expression level of ApoA-I was suggested as a specific and appropriate alternative to conventional HIV diagnosis and progression measurements in clinical research settings [83]. Increased concentration of ApoM in sera patients with HBV infection have been detected [84]. Recently, a downregulation of ApoA-I and ApoM levels have been associated with the severity of COVID-19 infection [85].
In addition to HDL, only other few lipoproteomic studies have been developed to discover changes in lipoproteins-associated proteins in diverse pathologies. Proteomic studies of LDL have reported that carry apolipoproteins AI, A-II, CI, C-II, C-III, C-IV, D, E, and F, in addition to apoB, as well as clusterin, C3, C4a, and C4b, and PON1 that are also associated to this particles [86]. Serum amyloid A levels were found to increase in all lipoprotein fractions, especially in LDL from atherosclerotic patients [24]. An enriched content of all the apoC-III isoforms and a lower content of apoA-I, apoC-I, and apoE were detected in the sdLDL from subjects with metabolic syndrome and subclinical peripheral atherosclerosis [87]. VLDL, IDL, and LDL fractions from Alzheimer patients exhibit low levels of complement C3 [88].
Target discovery, which is an important step in the drug development process, includes discovering and validating targets associated with the diseases. It is increasingly recognized that, in many instances, metabolomics is used to identify novel biomarkers, which can help in the discovery of therapeutic strategies for many diseases [89].
Until now, lipoproteomics has proved to be an effective method for identifying candidate cardiovascular disease markers. Studying the profiles of protein expression in drug-treated patients contributes to the discovery of multiple drug-specific targets. Traditionally, statin therapy has proven efficacy in reducing cardiovascular events, but as aforementioned, the identification of HDL-associated proteins is variable. The statin therapy has a notorious effect on the increment of A1AT associated to the large fraction of HDL particles enhancing its anti-inflammatory functionality, which may interfere with the statins outcome on reducing cholesterol levels [37]. In addition, a relationship between the CAD treatment and the HDL proteome was demonstrated using statin and niacin therapy, observing that ApoE and ApoC-II levels are enriched in the HDL3 fraction, which contains less ApoJ levels [90].
The increment in the HDL levels by CETP inhibitors is another biomarker that has continued to be disappointing in clinical research. In fact, in patients with deficiency of CETP (CETP-D), the HDL particles are enriched with ApoE, angiopoietin-like3 protein, and complement regulatory proteins such as C3, C4a, C4b, and C9 that could be associated to the increased atherogenic profile in CETP-D patients [91].
Thus, it is important to consider that among the diverse HDL populations not all possess a cardioprotective effect [92]. Therefore, we need a better knowledge of the protein cargo of the HDL populations with anti-atherogenic actions. A comprehensive understanding of the HDL proteomics can lead to the design of more effective anti-atherogenic drugs based on the activity of HDL-associated proteins that will provide new therapeutic strategies at the molecular level.
In the dynamic drug discovery process, the different proteomic methods, which include MS-proteomics, expand beyond the general aim of target drug discovery. It must consider the drug-protein interactions as well as elucidate the mode of action of candidate drug molecules [93]. Thus, novel HDL-based therapeutic agents, besides the traditional statins, will need consider to the functional HDL lipoproteomics to characterize the interaction of the drug with the HDL-associated proteins. This is necessary as an attempt either to elucidate the mechanism of action by direct drug-protein interaction or as a biomarker for drug validation by monitoring the pharmacological effect through an increase of HDL populations with an anti-atherogenic protein cargo.
The lipoproteins can be involved in different pathologies related to lipid metabolism such as atherosclerosis, cardiovascular risk, obesity, metabolic síndrome, and diabetes, among others. However, the protein cargo of these particles has been associated with several functions, which differ from the amply recognized as structural composition and receptors recognition during their function as lipid transporters. For this reason, the identification of variants of apolipoproteins and lipoprotein-associated proteins has been an important referent to detect new biomarkers. In fact, as we described here, several methodologies have been developed to improve the lipoproteomic profile.
Despite these studies, the majority concord that both biological source and lipoprotein purification are important steps to avoid protein contamination, principally from samples that are used directly as serum or plasma. Also, the most used method to identify the lipoprotein-associated proteins is the mass spectrometry, but some limits are presented that depend on the platforms to apply this methodology. Also, it is important to highlight that not everyone has the facility to use this methodology and it is necessary to develop new methodologies to apply in clinical fields to ensure discoveries about these proteins both in new lipoproteins’ fractions and new diseases.
Also, the lipoproteomic analyses could be a new clinical area to evaluate the therapy of the pathologies described here as prognostic analytes. In this sense, the HDL lipoproteomics is, perhaps, the more advanced field considering the evaluations of populations with statins’ treatment. However, novel HDL therapeutic agents must consider the functional lipoproteomics of these particles. Finally, these lipoproteomes can help us to describe the molecular mechanism to understand the interaction of apolipoproteins as well as the lipoprotein-carried proteins to support the other omics such as lipidomics and metabolomics.
This work was supported by the Autonomous University of Mexico City (UACM) awarded to MEAS.
The authors declare no conflict of interest.
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Paul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11044",title:"Dysphagia",subtitle:"New Advances",isOpenForSubmission:!1,hash:"8961f55525f51bd82d3daa09debd158f",slug:"dysphagia-new-advances",bookSignature:"Monjur Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/11044.jpg",editedByType:"Edited by",editors:[{id:"206355",title:"Associate Prof.",name:"Monjur",middleName:null,surname:"Ahmed",slug:"monjur-ahmed",fullName:"Monjur Ahmed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10473",title:"Sarcoidosis",subtitle:"New Perspectives",isOpenForSubmission:!1,hash:"4bffdfb8619408d0a5608527292b6985",slug:"sarcoidosis-new-perspectives",bookSignature:"Seyyed Shamsadin Athari and Entezar Mehrabi Nasab",coverURL:"https://cdn.intechopen.com/books/images_new/10473.jpg",editedByType:"Edited by",editors:[{id:"139889",title:"Dr.",name:"Seyyed Shamsadin",middleName:null,surname:"Athari",slug:"seyyed-shamsadin-athari",fullName:"Seyyed Shamsadin Athari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1854,seriesByTopicCollection:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:143,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],seriesByTopicTotal:3,mostCitedChapters:[{id:"19013",doi:"10.5772/21983",title:"Cell Responses to Surface and Architecture of Tissue Engineering Scaffolds",slug:"cell-responses-to-surface-and-architecture-of-tissue-engineering-scaffolds",totalDownloads:10520,totalCrossrefCites:134,totalDimensionsCites:305,abstract:null,book:{id:"314",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",title:"Regenerative Medicine and Tissue Engineering",fullTitle:"Regenerative Medicine and Tissue Engineering - Cells and Biomaterials"},signatures:"Hsin-I Chang and Yiwei Wang",authors:[{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang"},{id:"53659",title:"Ms.",name:"Yiwei",middleName:null,surname:"Wang",slug:"yiwei-wang",fullName:"Yiwei Wang"}]},{id:"46479",doi:"10.5772/57353",title:"Floating Drug Delivery Systems for Eradication of Helicobacter pylori in Treatment of Peptic Ulcer Disease",slug:"floating-drug-delivery-systems-for-eradication-of-helicobacter-pylori-in-treatment-of-peptic-ulcer-d",totalDownloads:2864,totalCrossrefCites:139,totalDimensionsCites:302,abstract:null,book:{id:"3839",slug:"trends-in-helicobacter-pylori-infection",title:"Trends in Helicobacter pylori Infection",fullTitle:"Trends in Helicobacter pylori Infection"},signatures:"Yousef Javadzadeh and Sanaz Hamedeyazdan",authors:[{id:"94276",title:"Prof.",name:"Yousef",middleName:null,surname:"Javadzadeh",slug:"yousef-javadzadeh",fullName:"Yousef Javadzadeh"},{id:"98229",title:"Dr.",name:"Sanaz",middleName:null,surname:"Hamedeyazdan",slug:"sanaz-hamedeyazdan",fullName:"Sanaz Hamedeyazdan"}]},{id:"25512",doi:"10.5772/30872",title:"Epidemiology of Psychological Distress",slug:"epidemiology-of-psychological-distress",totalDownloads:8820,totalCrossrefCites:95,totalDimensionsCites:256,abstract:null,book:{id:"727",slug:"mental-illnesses-understanding-prediction-and-control",title:"Mental Illnesses",fullTitle:"Mental Illnesses - Understanding, Prediction and Control"},signatures:"Aline Drapeau, Alain Marchand and Dominic Beaulieu-Prévost",authors:[{id:"84582",title:"Dr.",name:"Aline",middleName:null,surname:"Drapeau",slug:"aline-drapeau",fullName:"Aline Drapeau"},{id:"84605",title:"Dr.",name:"Alain",middleName:null,surname:"Marchand",slug:"alain-marchand",fullName:"Alain Marchand"},{id:"84606",title:"Dr.",name:"Dominic",middleName:null,surname:"Beaulieu-Prévost",slug:"dominic-beaulieu-prevost",fullName:"Dominic Beaulieu-Prévost"}]},{id:"64762",doi:"10.5772/intechopen.82511",title:"Mechanism and Health Effects of Heavy Metal Toxicity in Humans",slug:"mechanism-and-health-effects-of-heavy-metal-toxicity-in-humans",totalDownloads:10461,totalCrossrefCites:107,totalDimensionsCites:248,abstract:"Several heavy metals are found naturally in the earth crust and are exploited for various industrial and economic purposes. Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. The focus of this chapter is to describe the various mechanism of intoxication of some selected heavy metals in humans along with their health effects. Therefore it aims to highlight on biochemical mechanisms of heavy metal intoxication which involves binding to proteins and enzymes, altering their activity and causing damage. More so, the mechanism by which heavy metals cause neurotoxicity, generate free radical which promotes oxidative stress damaging lipids, proteins and DNA molecules and how these free radicals propagate carcinogenesis are discussed. Alongside these mechanisms, the noxious health effects of these heavy metals are discussed.",book:{id:"7111",slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",title:"Poisoning in the Modern World",fullTitle:"Poisoning in the Modern World - New Tricks for an Old Dog?"},signatures:"Godwill Azeh Engwa, Paschaline Udoka Ferdinand, Friday Nweke Nwalo and Marian N. Unachukwu",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",middleName:null,surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",middleName:null,surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",middleName:null,surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",middleName:null,surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}]},{id:"27687",doi:"10.5772/29869",title:"Heavy Metals and Human Health",slug:"heavy-metals-and-human-health",totalDownloads:18969,totalCrossrefCites:87,totalDimensionsCites:196,abstract:null,book:{id:"1012",slug:"environmental-health-emerging-issues-and-practice",title:"Environmental Health",fullTitle:"Environmental Health - Emerging Issues and Practice"},signatures:"Simone Morais, Fernando Garcia e Costa and Maria de Lourdes Pereira",authors:[{id:"13875",title:"Prof.",name:"Simone",middleName:null,surname:"Morais",slug:"simone-morais",fullName:"Simone Morais"},{id:"79715",title:"Prof.",name:"Maria De Lourdes",middleName:null,surname:"Pereira",slug:"maria-de-lourdes-pereira",fullName:"Maria De Lourdes Pereira"},{id:"87294",title:"Prof.",name:"Fernando",middleName:null,surname:"Garcia E Costa",slug:"fernando-garcia-e-costa",fullName:"Fernando Garcia E Costa"}]}],mostDownloadedChaptersLast30Days:[{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14512,totalCrossrefCites:33,totalDimensionsCites:56,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ozioma Ezekwesili-Ofili",slug:"josephine-ozioma-ezekwesili-ofili",fullName:"Josephine Ozioma Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"76640",title:"Control of Clinical Laboratory Errors by FMEA Model",slug:"control-of-clinical-laboratory-errors-by-fmea-model",totalDownloads:1208,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Patient safety is an aim for clinical applications and is a fundamental principle of healthcare and quality management. The main global health organizations have incorporated patient safety in their review of work practices. The data provided by the medical laboratories have a direct impact on patient safety and a fault in any of processes such as strategic, operational and support, could affect it. To provide appreciate and reliable data to the physicians, it is important to emphasize the need to design risk management plan in the laboratory. Failure Mode and Effect Analysis (FMEA) is an efficient technique for error detection and reduction. Technical Committee of the International Organization for Standardization (ISO) licensed a technical specification for medical laboratories suggesting FMEA as a method for prospective risk analysis of high-risk processes. FMEA model helps to identify quality failures, their effects and risks with their reduction/elimination, which depends on severity, probability and detection. Applying FMEA in clinical approaches can lead to a significant reduction of the risk priority number (RPN).",book:{id:"9808",slug:"contemporary-topics-in-patient-safety-volume-1",title:"Contemporary Topics in Patient Safety",fullTitle:"Contemporary Topics in Patient Safety - Volume 1"},signatures:"Hoda Sabati, Amin Mohsenzadeh and Nooshin Khelghati",authors:[{id:"340486",title:"M.Sc.",name:"Hoda",middleName:null,surname:"Sabati",slug:"hoda-sabati",fullName:"Hoda Sabati"},{id:"348872",title:"M.Sc.",name:"Amin",middleName:null,surname:"Mohsenzadeh",slug:"amin-mohsenzadeh",fullName:"Amin Mohsenzadeh"},{id:"348874",title:"MSc.",name:"Nooshin",middleName:null,surname:"Khelghati",slug:"nooshin-khelghati",fullName:"Nooshin Khelghati"}]},{id:"64762",title:"Mechanism and Health Effects of Heavy Metal Toxicity in Humans",slug:"mechanism-and-health-effects-of-heavy-metal-toxicity-in-humans",totalDownloads:10456,totalCrossrefCites:107,totalDimensionsCites:242,abstract:"Several heavy metals are found naturally in the earth crust and are exploited for various industrial and economic purposes. Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. The focus of this chapter is to describe the various mechanism of intoxication of some selected heavy metals in humans along with their health effects. Therefore it aims to highlight on biochemical mechanisms of heavy metal intoxication which involves binding to proteins and enzymes, altering their activity and causing damage. More so, the mechanism by which heavy metals cause neurotoxicity, generate free radical which promotes oxidative stress damaging lipids, proteins and DNA molecules and how these free radicals propagate carcinogenesis are discussed. Alongside these mechanisms, the noxious health effects of these heavy metals are discussed.",book:{id:"7111",slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",title:"Poisoning in the Modern World",fullTitle:"Poisoning in the Modern World - New Tricks for an Old Dog?"},signatures:"Godwill Azeh Engwa, Paschaline Udoka Ferdinand, Friday Nweke Nwalo and Marian N. Unachukwu",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",middleName:null,surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",middleName:null,surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",middleName:null,surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",middleName:null,surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}]},{id:"65467",title:"Anesthesia Management for Large-Volume Liposuction",slug:"anesthesia-management-for-large-volume-liposuction",totalDownloads:6203,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The apparent easiness with which liposuction is performed favors that patients, young surgeons, and anesthesiologists without experience in this field ignore the many events that occur during this procedure. Liposuction is a procedure to improve the body contour and not a surgery to reduce weight, although recently people who have failed in their plans to lose weight look at liposuction as a means to contour their body figure. Tumescent liposuction of large volumes requires a meticulous selection of each patient; their preoperative evaluation and perioperative management are essential to obtain the expected results. The various techniques of general anesthesia are the most recommended and should be monitored in the usual way, as well as monitoring the total doses of infiltrated local anesthetics to avoid systemic toxicity. The management of intravenous fluids is controversial, but the current trend is the restricted use of hydrosaline solutions. The most feared complications are deep vein thrombosis, pulmonary thromboembolism, fat embolism, lung edema, hypothermia, infections and even death. The adherence to the management guidelines and prophylaxis of venous thrombosis/thromboembolism is mandatory.",book:{id:"6221",slug:"anesthesia-topics-for-plastic-and-reconstructive-surgery",title:"Anesthesia Topics for Plastic and Reconstructive Surgery",fullTitle:"Anesthesia Topics for Plastic and Reconstructive Surgery"},signatures:"Sergio Granados-Tinajero, Carlos Buenrostro-Vásquez, Cecilia\nCárdenas-Maytorena and Marcela Contreras-López",authors:[{id:"273532",title:"Dr.",name:"Sergio Octavio",middleName:null,surname:"Granados Tinajero",slug:"sergio-octavio-granados-tinajero",fullName:"Sergio Octavio Granados Tinajero"}]},{id:"30178",title:"Chest Mobilization Techniques for Improving Ventilation and Gas Exchange in Chronic Lung Disease",slug:"chest-mobilization-techniques-for-improving-ventilation-and-gas-exchange-in-chronic-lung-disease",totalDownloads:31227,totalCrossrefCites:0,totalDimensionsCites:5,abstract:null,book:{id:"648",slug:"chronic-obstructive-pulmonary-disease-current-concepts-and-practice",title:"Chronic Obstructive Pulmonary Disease",fullTitle:"Chronic Obstructive Pulmonary Disease - Current Concepts and Practice"},signatures:"Donrawee Leelarungrayub",authors:[{id:"73709",title:"Associate Prof.",name:"Jirakrit",middleName:null,surname:"Leelarungrayub",slug:"jirakrit-leelarungrayub",fullName:"Jirakrit Leelarungrayub"}]}],onlineFirstChaptersFilter:{topicId:"3",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"77607",title:"Mentorship in Postgraduate Medical Education",slug:"mentorship-in-postgraduate-medical-education",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.98612",abstract:"Mentorship is critical to the development and professional growth of graduate medical education (GME) trainees. It is a bidirectional relationship between a mentor and a mentee. Mentorship has consistently been shown to be beneficial for both the mentor and mentee, with the mentee gaining valuable skills in education, personal growth, and professional support, and the mentor attaining higher career satisfaction and potentially greater productivity. Yet, there is a lack of research and in-depth analysis of effective mentorship and its role in postgraduate medical education. This chapter outlines different approaches toward mentorship and provides the reader with basic concepts relevant to the effective and competent practice of mentorship. The authors discuss the challenges that physician mentors and mentees face, the organizational models of mentorship, the approaches and techniques for mentorship, and the deleterious effects of mentorship malpractice. Our general discussion touches on best practices for both the mentor and mentee to allow for self-improvement and lifelong learning. The variety of applicable models makes it difficult to measure effectiveness of mentorship in GME, but there is an ongoing need for expanded research on the benefits of mentorship, as greater amount of supporting evidence will likely incentivize organizations to create mentorship-friendly policies and support corresponding institutional changes.",book:{id:"6947",title:"Contemporary Topics in Graduate Medical Education - Volume 2",coverURL:"https://cdn.intechopen.com/books/images_new/6947.jpg"},signatures:"Lena Deb, Shanaya Desai, Kaitlyn McGinley, Elisabeth Paul, Tamam Habib, Asim Ali and Stanislaw Stawicki"},{id:"81585",title:"Self-Management Strategies in Outpatients with Hypertension Under Treatment in Rural Communities",slug:"self-management-strategies-in-outpatients-with-hypertension-under-treatment-in-rural-communities",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.104447",abstract:"Hypertension is already a problem faced by South African urban populations, but little is known about the predominance, chance factors, and self-management strategies of hypertension in rural areas. Hypertension has an increased mortality and morbidity rate, thus has been identified as the killer disease in rural communities as its prevalence is increasing year by year. Non-attendance of hypertensive patients in rural communities has been identified as one of the most pressing issues in chronic illness, including hypertension, management and results into uncontrolled illnesses. Hypertensive patients lack self-management strategies to maintain their quality of life when diagnosed. Therefore, this book chapter is aimed at exploring the knowledge of self-management and strategies used in outpatients with hypertension under treatment in rural communities. Seven major themes were identified: paradoxical description; adherence to treatment and medication instructions, medical follow-up visits at the health facility, healthy lifestyle; management of emotions; defense mechanisms and religious interventions. Patients faced obstacles such as not eating a healthy diet since they are not the ones cooking, and children are always generating problems for them, leading their blood pressure and blood glucose levels to rise. Additional efforts are needed in rural communities to promote hypertension and self-management measures through educational programs.",book:{id:"11292",title:"Hypertension",coverURL:"https://cdn.intechopen.com/books/images_new/11292.jpg"},signatures:"Peter Modupi Mphekgwana, Tebogo Maria Mothiba and Nancy Kgatla"},{id:"82673",title:"Utilising Proteomics and Organoid Cultures for Predicting Treatment Response in Colorectal Cancer",slug:"utilising-proteomics-and-organoid-cultures-for-predicting-treatment-response-in-colorectal-cancer",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106028",abstract:"Colorectal cancer (CRC) remains one of the most frequently diagnosed tumours worldwide. Despite advances in surgical intervention and therapeutics, development of chemoresistance remains a challenge to treating CRC. Predicting treatment response in CRC has strongly relied on genomics, transcriptomics and epigenomics, combined with different cancer staging and classification systems. Despite being beneficial, these omics technologies fail to provide any assessment at a protein level. Thus, having high-throughput tools that assess tumour response to therapy at a protein level will definitely complement the current approaches. In this regard, the field of proteomics holds promise to understand treatment response in tumours. Additionally, patient-derived tumour organoids are replacing the traditional cell lines and xenograft models as the preferred in vitro models for predicting clinical response due to being a better representative model of typical tumour characteristics in vivo. Combining proteomics and tumour organoids can provide more personalised and optimal treatments for CRC in the coming years. This chapter aims to provide an overview of the progress made in proteomic research and use of organoids for understanding CRC treatment response, together with discussing the strengths and limitations of these two approaches when linked together. This overview will then be used to propose future perspectives.",book:{id:"11595",title:"Recent Understanding of Colorectal Cancer Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/11595.jpg"},signatures:"Isaac Micallef and Byron Baron"},{id:"81897",title:"Left Atrial Appendage Closure for Stroke Prevention",slug:"left-atrial-appendage-closure-for-stroke-prevention",totalDownloads:2,totalDimensionsCites:null,doi:"10.5772/intechopen.105140",abstract:"Atrial fibrillation is the most common chronic arrhythmia worldwide, and stroke is its most common complication. Approximately 20% of all ischemic strokes attributed to atrial fibrillation. Left atrial appendage thrombi are 90% responsible for embolic strokes in patients with non-valvular atrial fibrillation. In patients with atrial fibrillation, systemic anticoagulation is highly effective in lowering the risk of stroke. Bleeding problems and non-adherence hamper adequate anticoagulation therapy. As an alternative to stroke prevention with medical treatment, left atrial appendage closure is feasible and has proven to be an alternative to anticoagulation in non-valvular atrial fibrillation patients. Various left atrial appendage closure methods and devices have been defined and applied surgically and percutaneously. Exclusion of the left atrial appendage potentially minimizes the risk of embolic stroke and may eliminate chronic anticoagulation requirements. This chapter reviews left atrial appendage closure for stroke prevention in non-valvular atrial fibrillation.",book:{id:"11655",title:"Atrial Fibrillation - Diagnosis and Management in the 21st Century",coverURL:"https://cdn.intechopen.com/books/images_new/11655.jpg"},signatures:"Serkan Asil"},{id:"83106",title:"Portal Vein Thrombosis in Patients with β-Thalassemia",slug:"portal-vein-thrombosis-in-patients-with-thalassemia",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106564",abstract:"Beta (β)-thalassemia major, a chronic inherited hematological disease, leads to chronic anemia in affected children. One of the options for treatment is splenectomy. However, this treatment involves risk of many complications, one of which is portal vein thrombosis (PVT). The risk factors include exposure of phosphatidyl-serine of abnormal red blood cells (RBCs), increased activation, aggregation and a number of platelets and nucleated RBCs after splenectomy, increased endothelial activation, decreased nitric oxide, organ dysfunction, and thrombophilia. PVT is either complete or partial obstruction and has fatal complications, especially after splenectomy and late diagnosis without effective treatment. Diagnosis is typically made with X-ray. Generally, the incidence of PVT is between 1.7% and 9.2%. Initially, it is asymptomatic; symptoms appear gradually as thrombosis progresses. The easiest way to differentiate it from other conditions is via imaging study like Doppler ultrasound. It is usually associated with prolonged prothrombin time (PT). D-dimer and alkaline phosphatase are generally high. The treatment is the same for both the acute and chronic forms and includes the treatment of causal factors, prevention of thrombus extension, and achievement of patency of the portal vein via regular RBC transfusion and antithrombotic agents.",book:{id:"11725",title:"The Erythrocyte - A Unique Cell",coverURL:"https://cdn.intechopen.com/books/images_new/11725.jpg"},signatures:"Ahmed Shemran Mutlaq Alwataify, Husain Naji Alshammary and Ali Hadi Mahdi"},{id:"83108",title:"Congenital Adrenal Hyperplasia",slug:"congenital-adrenal-hyperplasia",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106520",abstract:"Congenital adrenal hyperplasia (CAH) is a rare pathology with an estimated incidence of 1:14,000–18,000 births. It includes a group of inherited diseases with autosomal recessive transmission. The genetic defect consists of mutations of the genes encoding the enzymes involved in adrenal and eventually gonadal steroidogenesis. The most common mutation is the gene encoding 21 hydroxylase the enzyme involved in cortisol and aldosterone synthesis. However, other enzymatic defects can be identified. The excess of steroid precursors in the adrenal cortex will be directed towards adrenal androgen synthesis. Finally, the clinical picture includes a series of manifestations specific to the enzymatic deficiency, the severity depending on the degree of the genetic defect. Thus, we can meet severe deficits with clinical expression in newborns and toddlers or partial, non-classical forms with manifestation in adolescence or adulthood. 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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. 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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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