Proteins In Body Fluids Research Articles

MultiSec: Multi-Task Deep Learning Improves Secreted Protein Discovery in Human Body Fluids

Prediction of secreted proteins in human body fluids is essential since secreted proteins hold promise as disease biomarkers. Various approaches have been proposed to predict whether a protein is secreted into a specific fluid by its sequence. However, there may be relationships between different human body fluids when proteins are secreted into these fluids. Current approaches ignore these relationships directly, and therefore their performances are limited. Here, we present MultiSec, an improved approach for secreted protein discovery to exploit relationships between fluids via multi-task learning. Specifically, a sampling-based balance strategy is proposed to solve imbalance problems in all fluids, an effective network is presented to extract features for all fluids, and multi-objective gradient descent is employed to prevent fluids from hurting each other. MultiSec was trained and tested in 17 human body fluids. The comparison benchmarks on the independent testing datasets demonstrate that our approach outperforms other available approaches in all compared fluids.

Aggregation and Binding-Directed FRET Modulation of Conjugated Polymer Materials for Selective and Point-of-Care Monitoring of Serum Albumins

Nonspecific interactions of conjugated polymers (CPs) with various proteins prove to be a major impediment for researchers when designing a suitable CP-based probe for the amplified and selective recognition of particular proteins in complex body fluids. Herein, a new strategy is presented for the precise and specific monitoring of clinically important serum albumin (SA) proteins at the nanomolar level using fluorescence resonance energy transfer (FRET)-modulated CP-surfactant ensembles as superior sensing materials. In brief, the newly designed color-tunable CP PF-DBT-Im undergoes intense aggregation with the surfactant sodium dodecyl sulfate (SDS), enabling drastic change in the emission color from violet to deep red due to intermolecular FRET. The emission of PF-DBT-Im/SDS ensembles then changed from deep red to magenta specifically on addition of SAs owing to the exclusive reverse FRET facilitated by synergistic effects of electrostatic interactions, hydrophobic forces, and the comparatively high intrinsic quantum yield of SAs. Interestingly, PF-DBT-Im itself could not differentiate SAs from other proteins, demonstrating the superiority of the PF-DBT-Im/SDS self-assembly over PF-DBT-Im. Finally, an affordable smartphone-integrated point-of-care (PoC) device is also fabricated as a proof-of-concept for the on-site and rapid monitoring of SAs, validating the potential of the system in long-term clinical applications.

Chemical Barrier Proteins in Human Body Fluids.

Chemical barriers are composed of those sites of the human body where potential pathogens can contact the host cells. A chemical barrier is made up by different proteins that are part of the antimicrobial and immunomodulatory protein/peptide (AMP) family. Proteins of the AMP family exert antibacterial, antiviral, and/or antifungal activity and can modulate the immune system. Besides these proteins, a wide range of proteases and protease inhibitors can also be found in the chemical barriers maintaining a proteolytic balance in the host and/or the pathogens. In this review, we aimed to identify the chemical barrier components in nine human body fluids. The interaction networks of the chemical barrier proteins in each examined body fluid were generated as well.

Supplementary material for "Chemical barrier proteins in human body fluids"

Supplementary material for "Chemical barrier proteins in human body fluids"

Supplementary material for "Chemical barrier proteins in human body fluids"

Supplementary material for "Chemical barrier proteins in human body fluids"

Proteins in human body fluids contain in vivo antigen analog of the melibiose-derived glycation product: MAGE

Melibiose-derived AGE (MAGE) is an advanced glycation end-product formed in vitro in anhydrous conditions on proteins and protein-free amino acids during glycation with melibiose. Our previous studies revealed the presence of MAGE antigen in the human body and tissues of several other species, including muscles, fat, extracellular matrix, and blood. MAGE is also antigenic and induces generation of anti-MAGE antibody. The aim of this paper was to identify the proteins modified by MAGE present in human body fluids, such as serum, plasma, and peritoneal fluids. The protein-bound MAGE formed in vivo has been isolated from human blood using affinity chromatography on the resin with an immobilized anti-MAGE monoclonal antibody. Using mass spectrometry and immunochemistry it has been established that MAGE epitope is present on several human blood proteins including serum albumin, IgG, and IgA. In serum of diabetic patients, mainly the albumin and IgG were modified by MAGE, while in healthy subjects IgG and IgA carried this modification, suggesting the novel AGE can impact protein structure, contribute to auto-immunogenicity, and affect function of immunoglobulins. Some proteins in peritoneal fluid from cancer patients modified with MAGE were also observed and it indicates a potential role of MAGE in cancer.

A direct method for detecting proteins in body fluids by Surface-Enhanced Raman Spectroscopy under native conditions

Surface enhanced Raman spectroscopy (SERS) is widely used in biomolecular detection. However, maintaining the native structure of proteins while obtaining sensitive and reproducible SERS signals of unlabeled proteins remains a challenge. In this study, dichloromethane (DCM) and CaCl2 were used to optimize the aggregation of Ag nanoparticles (AgNPs), and several proteins were analyzed comprehensively. Calcium ions removed citrate ions outside AgNPs, inducing hot spots and achieving high-sensitivity SERS signals of proteins. Furthermore, 20 random samples of 0.5 μg/mL hemoglobin were analyzed by this method. The obtained spectra showed good repeatability and a high quality. Using the peak intensity of DCM as internal parameter, the differences in peak intensities at the same position were analyzed to distinguish different proteins and evaluate changes in protein structure. Subsequently, the protein content in protein mixtures and serum was quantified and a good linear relationship between peak intensity and protein concentration was obtained. This method shows great promise in the fields of food testing and clinical diagnosis.

Near‐Infrared Multilayer MoS2 Photoconductivity‐Enabled Ultrasensitive Homogeneous Plasmonic Colorimetric Biosensing

AbstractThe ability to detect low‐abundance proteins in human body fluids plays a critical role in proteomic research to achieve a comprehensive understanding of protein functions and early‐stage disease diagnosis to reduce mortality rates. Ultrasensitive (sub‐fM), rapid, simple “mix‐and‐read” plasmonic colorimetric biosensing of large‐size (≈180 kDa) proteins in biofluids using an ultralow‐noise multilayer molybdenum disulfide (MoS2) photoconducting channel is reported here. With its out‐of‐plane structure optimized to minimize carrier scattering, the multilayer MoS2 channel operated under near‐infrared illumination enables the detection of a subtle plasmonic extinction shift caused by antigen‐induced nanoprobe aggregation. The demonstrated biosensing strategy allows quantifying carcinoembryonic antigen in unprocessed whole blood with a dynamic range of 106, a sample‐to‐answer time of 10 min, and a limit of detection of 0.1–3 pg mL−1, which is ≈100‐fold more sensitive than the clinical‐standard enzyme‐linked immunosorbent assays. The biosensing methodology can be broadly used to realize timely personalized diagnostics and physiological monitoring of diseases in point‐of‐care settings.

Bacterial meningitis without pyrexia after spinal anesthasia for caesarean section: A case report.

Introduction and importancyMeningitis happening in post spinal anesthesia is rare. But it has potentially life threatening or permanent neurological sequel if delayed or left untreated. The cause can be infectious or noninfectious. In this case, uncommon pathogen is described causing bacterial meningitis. Incidence varies from 0% to 0.04%.Case presentationA term pregnant lady came to the Operation room (OR) for an emergency caesarian section(C/S) because of cervical dystocia. She has no history of known medical illness. The anesthetist planned to administer spinal anesthesia. Under aseptic technique, the senior anesthetist wore a tight-fitting surgical mask, cap, and sterile gloves after hand hygiene with alcohol-based solutions.In sitting positioning between L(lumbar) 3 and L4 interspaces 10 mg bupivacaine +10 μg fentanyl was administered. Surgery and anesthesia were uneventful, 16 h into the postoperative period the mother develop severe headache, agitation, confusion, and forgetfulness.She has no fever but meningeal sign was positive. Lumbar puncture (LP) reveals purulent cerebrospinal fluid (CSF).Immediately, empirical treatment began. CSF sent for analysis and Culture, hematology, urinalysis, and organ function tests requested. Diagnosis was confirmed by clinical picture, low CSF glucose, and high body fluid protein, culture growth; showed Escherichia coli (E.coli). Treatment was instituted and patient has recovered fully.Clinical discussionE.coli is a very rare cause of bacterial meningitis but manifests a similar clinical picture like other bacterial meningitis but in our case no pyrexia. We believe there is a sterility breach somewhere in the process. The use of hospital sterilized spinal set, multidose antiseptics; institute sterility practice might be challenged.ConclusionThe use of modern packaging is recommended. Despite absent of pyrexia empiric treatment must start earlier besides the application of national guideline developed by the Joint Commission of different associations including America society of regional anesthesia (ASRA) is recommended.

A study of serum electrolytes level in viral hepatitis E patients in a tertiary care hospital of south Gujarat

Background: the aim of the study was to find and understand the relation between electrolytes and viral hepatitis E. To study electrolyte abnormality in patients with hepatitis E virus (HEV).Methods: This study is a single centre cross sectional study on the patients with HEV infection. Consecutive cases affected with HEV-at department of medicine, SMIMER (Surat Municipal institute of medical education and research) hospital, Surat during the period of 1 year (July-2019 to June-2020) are taken up for the study.Results: Abnormal electrolytes are associated with higher mortality in patients infected with HEV.Conclusions: A higher mean serum creatinine, total bilirubin, SGOT, SGPT; lower total protein, albumin, and abnormal electrolytes in body fluid (Na+, K+, Cl-, Ca++) values are associated with higher mortality in patients infected with HEV.

HBFP: a new repository for human body fluid proteome.

Body fluid proteome has been intensively studied as a primary source for disease biomarker discovery. Using advanced proteomics technologies, early research success has resulted in increasingly accumulated proteins detected in different body fluids, among which many are promising biomarkers. However, despite a handful of small-scale and specific data resources, current research is clearly lacking effort compiling published body fluid proteins into a centralized and sustainable repository that can provide users with systematic analytic tools. In this study, we developed a new database of human body fluid proteome (HBFP) that focuses on experimentally validated proteome in 17 types of human body fluids. The current database archives 11 827 unique proteins reported by 164 scientific publications, with a maximal false discovery rate of 0.01 on both the peptide and protein levels since 2001, and enables users to query, analyze and download protein entries with respect to each body fluid. Three unique features of this new system include the following: (i) the protein annotation page includes detailed abundance information based on relative qualitative measures of peptides reported in the original references, (ii) a new score is calculated on each reported protein to indicate the discovery confidence and (iii) HBFP catalogs 7354 proteins with at least two non-nested uniquely mapping peptides of nine amino acids according to the Human Proteome Project Data Interpretation Guidelines, while the remaining 4473 proteins have more than two unique peptides without given sequence information. As an important resource for human protein secretome, we anticipate that this new HBFP database can be a powerful tool that facilitates research in clinical proteomics and biomarker discovery.Database URL: https://bmbl.bmi.osumc.edu/HBFP/

Influence of bovine serum albumin on biodegradation behavior of pure Zn.

Zinc is emerging as a promising biodegradable metal for temporary implant applications. In this work, we investigate the influence of bovine serum albumin (BSA)-the most abundant blood protein in simulated body fluid (SBF) on degradation of pure Zn via electrochemical measurements and long-term immersion. Electrochemical experiments indicate a decrease of the corrosion rate of bare Zn with increasing BSA concentration in solution for short-term exposures. Samples were characterized with scanning electron microscope (SEM) (including energy dispersive spectroscopy [EDS], X-ray photoelectron spectroscopy [XPS], Fourier transform infrared spectroscopy [FTIR], and time-of-flight secondary ion mass spectrometry [TOF-SIMS]) after immersion up to 21 days. Presence of BSA in the electrolyte, decrease the amount of Ca-phosphate precipitation on Zn surface. However, a more compact surface layer formed in the presence of BSA in solution. Most noteworthy, in long-term exposures, BSA enhances localized corrosion of Zn-such detrimental localized attack was not observed in BSA-free solution. We suggest that a sealed space forming between the Zn substrate and a protein adsorption layer restricts mass transport, thus triggering localized corrosion of Zn.

In silico data mining of human body fluids to unravel the immunomes in breast cancer

Breast cancer is asymptomatic with a poor prognosis at late stage. We used in-silico based proteomics data mining to identify immunoproteins in body fluids as potential indicators of onset and progression of breast cancer. We curated a list of differentially expressed proteins in tissue and body fluids (e.g. saliva and blood) on subtype and non-subtype specific breast cancer over the last 20 years, to show the extent of similarities in protein expression in tissue and bio-fluids. Based on specific selection criteria, significantly altered proteins were filtered to functionally annotate and analyze using different databases. Furthermore, the immunoproteins that showed cross-talks were further analyzed for amino-acid sequence-specific alterations associated with breast cancer to predict their potential impact on the disease. The curated datasets consolidated 4716 non-redundant proteins collectively in tissue, blood, and saliva from literature focused on subtype or non-subtype specific breast cancer. Of these immunoproteins, 39 (e.g., saliva) and 20 (e.g., blood) were found to cross-talk, of which 28 and 6 from saliva and blood, respectively, showed amino acid variations and were associated with breast cancer. Similarly, a total of 92 and 10 driver mutants were identified in saliva and blood, respectively, with ‘deleterious’ or ‘damaging’ impact on the biological function of a protein. The results of the study established correlations between expression profile and variation of immunoproteins with breast cancer to assess the cumulative effect of mutational hotspots and identify proteome-scale alterations that could trigger abnormal cell behavior.

Plasma Proteomes Can Be Reidentifiable and Potentially Contain Personally Sensitive and Incidental Findings

AbstractThe goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual—beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of—and argue for the desirability for—ethical and human-rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

Deep Dive on the Proteome of Human Body Fluids: A Valuable Data Resource for Biomarker Discovery.

Body fluids are considered to be a rich source of disease biomarkers. Proteins in many body fluids have potential clinical applications for disease diagnostic and prognostic purposes. The aim of this study was to establish an in-depth multi-body fluid proteome. Ten body fluids associated with 8 types of cancers collected from 23 patients involved in 19 common diseases underwent liquid chromatography tandem mass spectrometry (MS) analysis after gel-based protein separation (SDS-PAGE) or peptide-based fractionations. Bioinformatic analysis, including principal component analysis (PCA), consensus clustering, and hierarchical clustering analysis were also performed. The biological function was determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). We profiled the proteome of ten body fluids, including ascites, bile, cerebrospinal fluid (CSF), hydrothorax, knee joint fluid (KJF), plasma, saliva, serum, tears, and urine. A total of 3,396 nonredundant proteins were identified, of which 304 were shared among ten body fluids, with common functions in focal adhesion and complement/coagulation cascades. A total of 41.5% (1,409) of the proteins were detected in only one body fluid and were closely related to their adjacent tissues by function. The functional analysis of the remaining 1,683 proteins showed that similar functions might be shared among different body fluids, which further highlighted the close connection of body fluids in the human body. A deep proteome of multi-body fluids originated from patients diagnosed with 19 common diseases provides a valuable data resource, and might indicate the potential application of body fluids for biomarker discovery.

Reverse Phase Protein Arrays.

Reverse phase protein arrays (RPPA) are used to quantify proteins and protein posttranslational modifications in cellular lysates and body fluids. RPPA technology is suitable for biomarker discovery, protein pathway profiling, functional phenotype analysis, and drug discovery mechanism of action. The principles of RPPA technology are (a) immobilizing protein-containing specimens on a coated slide in discrete spots, (b) antibody recognition of proteins, (c) amplification chemistries to detect the protein-antibody complex, and (d) quantifying spot intensity. Construction of a RPPA begins with the robotic liquid transfer of protein-containing specimens from microtiter plates onto nitrocellulose-coated slides. The robotic arrayer deposits each sample as discrete spots in an array format. Specimens, controls, and calibrators are printed on each array, thus providing a complete calibrated assay on a single slide. Each RPPA slide is subsequently probed with catalyzed signal amplification chemistries and a single primary antibody, a secondary antibody, and either fluorescent or colorimetric dyes. The focus of this chapter is to describe RPPA detection and imaging using a colorimetric (diaminobenzidine (DAB)) detection strategy.

Implementation of MALDI Mass Spectrometry Imaging in Cancer Proteomics Research: Applications and Challenges.

Studying the proteome–the entire set of proteins in cells, tissues, organs and body fluids—is of great relevance in cancer research, as differential forms of proteins are expressed in response to specific intrinsic and extrinsic signals. Discovering protein signatures/pathways responsible for cancer transformation may lead to a better understanding of tumor biology and to a more effective diagnosis, prognosis, recurrence and response to therapy. Moreover, proteins can act as a biomarker or potential drug targets. Hence, it is of major importance to implement proteomic, particularly mass spectrometric, approaches in cancer research, to provide new crucial insights into tumor biology. Recently, mass spectrometry imaging (MSI) approaches were implemented in cancer research, to provide individual molecular characteristics of each individual tumor while retaining molecular spatial distribution, essential in the context of personalized disease management and medicine.

Detection of lysozyme in body fluid based on two-dimensional colloidal crystal sensor

It is significant to detect lysozyme both in fundamental research and in clinical practice, since its concentration in body fluid is associated with many diseases. In this study, a new kind of sensor for rapid screening the lysozyme was fabricated based on the two-dimensional (2D) polystyrene colloidal crystal array together with the optimized hydrogel containing acrylamide-based functional groups. Distinct hydrogel volume shrink was observed due to the hydrogel crosslink induced by the functional ligand–protein interactions while the protein bound to the sensor. Therefore, the analyte concentration could be accessed by of the lattice spacing of the 2D colloidal crystal array, which was detected by a change in the Debye diffraction ring diameter. The lysozyme concentration could be easily monitored by measuring the diameter of the Debye diffraction ring in the pathophysiologic range. The particle spacing of 2D colloidal crystal hydrogel sensor increased to about 22 nm while lysozyme concentration increased from zero to 1.0 mg/mL, meanwhile the structural color of the sensor blue shifted from red to yellow. The detection limit was confirmed as 1.38 × 10−3 mg/mL. The selective response to other common proteins in body fluids was also exhibited, indicating the great selective response properties to lysozyme. In addition, the 2D colloidal crystal hydrogel sensor was reusable to detect the lysozyme solution reversibly due to its thermal sensitivity. Moreover, the determination of lysozyme in artificial tears and human urine samples by this sensor demonstrated its feasibility in potential clinical analysis diagnosis.

Post-Stroke Cognitive Impairment: A Review Focusing on Molecular Biomarkers.

Post-stroke cognitive impairment (PSCI), as one of the major complications after stroke, refers to a series of syndromes from mild cognitive impairment to dementia caused by stroke. Stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. The assessment of PSCI usually relies on neuropsychological tests, but the results of these tests are subjective and inaccurate, and can be insufficient for the diagnosis and prognosis of PSCI. In recent years, an increasing number studies have indicated that changes in the expression of biomarkers such as C-reactive protein (CRP), interleukin 6 (IL-6) and IL-10 in blood, urine and other body fluids are associated with cognitive decline after stroke. Therefore, the detection of biomarkers in circulating blood serum, plasma and cerebrospinal fluid (CSF) may improve the accuracy of diagnosis and prognosis in PSCI. This review aims to summarize the studies on potential molecular biomarkers of PSCI.

A Cole‐Cole Dielectric Relaxation Analysis of Albumin and γ‐Globulins for Protein Quantification by Electrical Impedance Spectroscopy

AbstractOptimal serum protein concentrations are vital for normal body functioning. Affordable while accurate protein quantification methods with minimum processing requirements are needed for diagnosis of related diseases. The standard automated chemistry analyzer is limited by high installation and maintenance costs. This study proposes the use of electrical impedimetric spectroscopy (EIS) as an alternative to current methods. Its practical applicability was tested using albumin and γ‐globulin or their miscellanea in three different media; water, serum and tissue‐mimicking phantoms at 25 °C. Impedance measurements were taken between frequency f=0.10 MHz to 300 MHz by an impedance analyzer. A Cole‐Cole analysis was used to elucidate the stepwise variations in the dielectric parameters of the protein medium so as to obtain empirical dielectric parameter‐protein concentration relationships and their correlation coefficients R2. From the results, linear relationships between parameters and protein concentrations with high correlation coefficients over R2=0.90 were observed. Resistance to charge transfer Rct and characteristic frequency fc were significantly altered by changing protein concentrations as compared to bulk solution resistance Rs, relaxation time constant τ and shape factor α. The relationships developed would aid in monitoring changes in body fluid protein concentrations by EIS.