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Proteomics and blood biomarkers

Santosh D Bhosale, Robert Moulder, Mikko S Venäläinen, Juhani S Koskinen, Niina Pitkänen, Markus T Juonala, Mika A P Kähönen, Terho J Lehtimäki, Jorma S A Viikari, Laura L Elo, David R Goodlett, Riitta Lahesmaa, Olli T Raitakari
To evaluate the presence of serum protein biomarkers associated with the early phases of formation of carotid atherosclerotic plaques, label-free quantitative proteomics analyses were made for serum samples collected as part of The Cardiovascular Risk in Young Finns Study. Samples from subjects who had an asymptomatic carotid artery plaque detected by ultrasound examination (N = 43, Age = 30-45 years) were compared with plaque free controls (N = 43) (matched for age, sex, body weight and systolic blood pressure)...
June 15, 2018: Scientific Reports
Francesca Raimondo, Clizia Chinello, Martina Stella, Lucia Santorelli, Fulvio Magni, Marina Pitto
Hematuria is a common sign of many renal and urologic pathologic conditions and it may affect the proteomic analysis of urinary extracellular vesicles (UEv), nanovesicles released from all cells in contact with the urinary space. This condition hinders UEv based proteomic studies aiming to discover biomarkers. Therefore, we studied the effects of hematuria on the proteome of UEv, and introduced a possible solution to reduce its misleading impact. We mimicked hematuria by adding increasing amount of blood to non-affected urine, and investigated its effects on UEv isolation, purity and proteomic composition...
June 15, 2018: Journal of Proteome Research
Qiuyue Liu, Liping Pan, Fen Han, Baojian Luo, Hongyan Jia, Aiying Xing, Qi Li, Zongde Zhang
Severe pulmonary tuberculosis (STB) is a life‑threatening condition with high economic and social burden. The present study aimed to screen for distinct proteins in different stages of TB and identify biomarkers for a better understanding of TB progression and pathogenesis. Blood samples were obtained from 81 patients with STB, 80 with mild TB (MTB) and 50 healthy controls. Differentially expressed proteins were identified using liquid chromatography‑tandem mass spectrometry‑based label‑free quantitative proteomic analysis...
June 5, 2018: Molecular Medicine Reports
Ruzanna Mnatsakanyan, Gerta Shema, Mark Basik, Gerald Batist, Christoph H Borchers, Albert Sickmann, René P Zahedi
Numerous diseases are caused by changes in post-translational modifications (PTMs). Therefore, the number of clinical proteomics studies that include the analysis of PTMs is increasing. Combining complementary information - e.g., changes in protein abundance, PTM levels, with the genome and transcriptome (proteogenomics) - holds great promise for discovering important drivers and markers of disease, as variations in copy number, expression levels, or mutations without spatial/functional/isoform information is often insufficient or even misleading...
June 12, 2018: Expert Review of Proteomics
Cian P McCarthy, Nasrien E Ibrahim, Roland R J van Kimmenade, Hanna K Gaggin, Mandy L Simon, Parul Gandhi, Noreen Kelly, Shweta R Motiwala, Renata Mukai, Craig A Magaret, Grady Barnes, Rhonda F Rhyne, Joseph M Garasic, James L Januzzi
BACKGROUND: Peripheral arterial disease (PAD) is a global health problem that is frequently underdiagnosed and undertreated. Non-invasive tools to predict the presence and severity of PAD have limitations including inaccuracy, cost, or need for intravenous contrast and ionizing radiation. HYPOTHESIS: A clinical/biomarker score may offer an attractive alternative diagnostic method. METHODS: In a prospective cohort of 354 patients referred for diagnostic peripheral and/or coronary angiography, predictors of ≥50% stenosis in at least one peripheral vessel (carotid/subclavian, renal, or lower extremity) were identified from over fifty clinical variables and 109 biomarkers...
June 6, 2018: Clinical Cardiology
Benjamin B Sun, Joseph C Maranville, James E Peters, David Stacey, James R Staley, James Blackshaw, Stephen Burgess, Tao Jiang, Ellie Paige, Praveen Surendran, Clare Oliver-Williams, Mihir A Kamat, Bram P Prins, Sheri K Wilcox, Erik S Zimmerman, An Chi, Narinder Bansal, Sarah L Spain, Angela M Wood, Nicholas W Morrell, John R Bradley, Nebojsa Janjic, David J Roberts, Willem H Ouwehand, John A Todd, Nicole Soranzo, Karsten Suhre, Dirk S Paul, Caroline S Fox, Robert M Plenge, John Danesh, Heiko Runz, Adam S Butterworth
Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases...
June 2018: Nature
Rocco Adiutori, Johan Aarum, Irene Zubiri, Michael Bremang, Stephan Jung, Denise Sheer, Ian Pike, Andrea Malaspina
Protein aggregation in biofluids is a poorly understood phenomenon. Under normal physiological conditions, fluid-borne aggregates may contain plasma or cell proteins prone to aggregation. Recent observations suggest that neurofilaments (Nf), the building blocks of neurons and a biomarker of neurodegeneration, are included in high molecular weight complexes in circulation. The composition of these Nf-containing hetero-aggregates (NCH) may change in systemic or organ-specific pathologies, providing the basis to develop novel disease biomarkers...
July 2018: Biochemistry and Biophysics Reports
David C Hondius, Kristel N Eigenhuis, Tjado H J Morrema, Roel C van der Schors, Pim van Nierop, Marianna Bugiani, Ka Wan Li, Jeroen J M Hoozemans, August B Smit, Annemieke J M Rozemuller
Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) deposits as plaques in the parenchyma and in the walls of cortical and leptomeningeal blood vessels of the brain called cerebral amyloid angiopathy (CAA). It is suggested that CAA type-1, which refers to amyloid deposition in both capillaries and larger vessels, adds to the symptomatic manifestation of AD and correlates with disease severity. Currently, CAA cannot be diagnosed pre-mortem and disease mechanisms involved in CAA are elusive. To obtain insight in the disease mechanism of CAA and to identify marker proteins specifically associated with CAA we performed a laser dissection microscopy assisted mass spectrometry analysis of post-mortem human brain tissue of (I) AD cases with only amyloid deposits in the brain parenchyma and no vascular related amyloid, (II) AD cases with severe CAA type-1 and no or low numbers of parenchymal amyloid deposits and (III) cognitively healthy controls without amyloid deposits...
June 4, 2018: Acta Neuropathologica Communications
Kim Lategan, Jodi Fowler, Mohamed Bayati, Maria Fidalgo de Cortalezzi, Edmund Pool
Carbon dots (CDs) are engineered nanoparticles that are used in a number of bioapplications such as bioimaging, drug delivery and theranostics. The effects of CDs on the immune system have not been evaluated. The effects of CDs on the immune system were assessed by using RAW 264.7 cells and whole blood cell cultures. RAW cells were exposed to CD concentrations under basal conditions. Whole blood cell cultures were exposed to CD concentrations under basal conditions or in the presence of the mitogens, lipopolysaccharide (LPS) or phytohaemmagglutinin (PHA)...
May 31, 2018: Nanomaterials
F Girolami, P Badino, V Spalenza, L Manzini, G Renzone, A M Salzano, F Dal Piaz, A Scaloni, G Rychen, C Nebbia
Dioxins and polychlorinated biphenyls (PCBs) are widespread and persistent contaminants. Through a combined gene expression/proteomic-based approach, candidate biomarkers of the exposure to such environmental pollutants in cattle subjected to a real eco-contamination event were identified. Animals were removed from the polluted area and fed a standard ration for 6 months. The decontamination was monitored by evaluating dioxin and PCB levels in pericaudal fat two weeks after the removal from the contaminated area (day 0) and then bimonthly for six months (days 59, 125 and 188)...
May 28, 2018: Science of the Total Environment
Tatjana Sajic, Yansheng Liu, Eirini Arvaniti, Silvia Surinova, Evan G Williams, Ralph Schiess, Ruth Hüttenhain, Atul Sethi, Sheng Pan, Teresa A Brentnall, Ru Chen, Peter Blattmann, Betty Friedrich, Emma Niméus, Susanne Malander, Aurelius Omlin, Silke Gillessen, Manfred Claassen, Ruedi Aebersold
Cancer is mostly incurable when diagnosed at a metastatic stage, making its early detection via blood proteins of immense clinical interest. Proteomic changes in tumor tissue may lead to changes detectable in the protein composition of circulating blood plasma. Using a proteomic workflow combining N-glycosite enrichment and SWATH mass spectrometry, we generate a data resource of 284 blood samples derived from patients with different types of localized-stage carcinomas and from matched controls. We observe whether the changes in the patient's plasma are specific to a particular carcinoma or represent a generic signature of proteins modified uniformly in a common, systemic response to many cancers...
May 29, 2018: Cell Reports
William F Blakely, David L Bolduc, Jeff Debad, George Sigal, Matthias Port, Michael Abend, Marco Valente, Michel Drouet, Francis Hérodin
Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.25 cGy min and 32 cGy min. Hematopoietic acute radiation syndrome severity levels determined by an analysis of blood count changes measured up to 60 d after irradiation were used to gauge overall hematopoietic acute radiation syndrome severity classifications...
July 2018: Health Physics
Christina Looße, Frauke Swieringa, Johan W M Heemskerk, Albert Sickmann, Christin Lorenz
Platelets are the smallest cells within the circulating blood with key roles in physiological haemostasis and pathological thrombosis regulated by the onset of activating/inhibiting processes via receptor responses and signalling cascades. Areas covered: Proteomics as well as genomic approaches have been fundamental in identifying and quantifying potential targets for future diagnostic strategies in the prevention of bleeding and thrombosis, and uncovering the complexity of platelet functions in health and disease...
May 22, 2018: Expert Review of Proteomics
Sandra I Anjo, Bruno Manadas
The identification of circulating biomarkers capable of being used as routine for diagnosis, prognosis, risk stratification and therapeutic monitoring is still the major aim at clinical proteomics. However, the direct search in blood samples or other clinical relevant biofluids is frequently associated with technical limitations that makes the biomarker discovery process extremely difficult when using these types of samples. In this sense, the use of different approaches, such as the analysis of cells' secretomes, can be an important and promising complementary method for the identification and pre-selection of potential circulating biomarkers...
May 18, 2018: Biochimie
John D Lapek, Robert H Mills, Jacob M Wozniak, Anaamika Campeau, Ronnie H Fang, Xiaoli Wei, Kirsten van de Groep, Araceli Perez-Lopez, Nina M van Sorge, Manuela Raffatellu, Rob Knight, Liangfang Zhang, David J Gonzalez
Group A Streptococcus (GAS) remains one of the top 10 deadliest human pathogens worldwide despite its sensitivity to penicillin. Although the most common GAS infection is pharyngitis (strep throat), it also causes life-threatening systemic infections. A series of complex networks between host and pathogen drive invasive infections, which have not been comprehensively mapped. Attempting to map these interactions, we examined organ-level protein dynamics using a mouse model of systemic GAS infection. We quantified over 11,000 proteins, defining organ-specific markers for all analyzed tissues...
April 28, 2018: Cell Systems
E Suguna, R Farhana, E Kanimozhi, P SaiKumar, G Kumaramanickavel, Chitralekha Sai Kumar
Background &Objective: Acute myeloid leukemia (AML) is characterized by accumulation of ?20% myeloid premature blast cells in the bone marrow and most often found in the peripheral blood. AML is generally classified based on two groups, namely, French-American-British (FAB) and World Health Organization (WHO) systems. For better clinical management, cytogenetic findings in AML are necessary and in patients with normal karyotypes, molecular analysis becomes critical. Mutations of certain genes like Nucleophosmin 1gene (NPM1), Fms-related Tyrosine Kinase 3 (FLT3), CCAAT/Enhancer Binding Protein Alpha (CEBPA), Runt-related transcription factor 1(RUNX1), and Mixed Lineage Leukemia (MLL) play a crucial role in the risk management and clinical stratification of AML patients...
May 15, 2018: Cardiovascular & Hematological Disorders Drug Targets
Mackenzie M Honikel, Chi-En Lin, David Probst, Jeffrey T La Belle
Cardiovascular disease (CVD) accounts for 30% of all global deaths and is predicted to dominate in the coming years, despite vast improvements in medical technology. Current clinical methods of assessing an individual's cardiovascular health include blood tests to monitor relevant biomarker levels as well as varying imaging modalities such as electrocardiograms, computed tomography, and angiograms to assess vasculature. As informative as these tools are, they each require lengthy scheduling, preparation, and highly trained personnel to interpret the results before any information is accessible to patients, often leading to delayed treatment, which can be fatal...
2018: Critical Reviews in Biomedical Engineering
Gustavo Diaz, Chandler Bridges, Megan Lucas, Yong Cheng, Jeff S Schorey, Karen M Dobos, Nicole A Kruh-Garcia
Exosomes, a type of nanovesicle released from all cell types, can be isolated from any bodily fluid. The contents of exosomes, including proteins and RNAs, are unique to the cells from which they are derived and can be used as indicators of disease. Several common enrichment protocols, including ultracentrifugation, yield exosomes laden with soluble protein contaminants. Specifically, we have found that the most abundant proteins within blood often co-purify with exosomes and can confound downstream proteomic studies, thwarting the identification of low abundance biomarker candidates...
April 13, 2018: Journal of Visualized Experiments: JoVE
Cecilie Rosting, Jinglei Yu, Helen J Cooper
Despite the great potential of Dried Blood Spots (DBS) as a source of endogenous proteins for biomarker discovery, the literature relating to non-targeted bottom-up proteomics of DBS is sparse, primarily due to the inherent complexity and very high dynamic range associated with these samples. Here, we present proof-of-concept results in which we have coupled high field asymmetric waveform ion mobility spectrometry (FAIMS) with LC-MS/MS for non-targeted bottom-up proteomics of DBS with the aim of addressing these challenges...
April 30, 2018: Journal of Proteome Research
Li-Hua Zhou, Jian-Ya Xu, Chen Dai, Yi-Man Fan, Bin Yuan
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid (QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL...
April 2018: Chinese Journal of Natural Medicines
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