| 1. |
- Bratlie, Svein-Olav, et al.
(författare)
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Proteomic Approach to the Potential Role of Angiotensin II in Barrett Dysplasia
- 2019
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Ingår i: Proteomics - Clinical Applications. - : Wiley. - 1862-8346 .- 1862-8354. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Dysplasia in Barrett's esophagus (BE) is regarded as a preneoplastic lesion. The renin–angiotensin system (RAS), known for its role in electrolyte homeostasis and hemodynamics, has also been shown to have tissue-based features linked to proliferation, inflammation, and cancer. RAS is associated with BE dysplasia. The aim of this study is to investigate possible effects of the RAS in BE dysplasia by using RAS-interfering pharmaceutical agents and by assessment of global protein expression in esophageal mucosal biopsies. Methods: Endoscopic biopsies are taken from 18 BE in patients with low-grade dysplasia before and after 3 weeks of treatment with either angiotensin-converting enzyme inhibitors (enalapril 5 mg; n = 6) or angiotensin II receptor type 1 blockers (candesartan 8 mg; n = 6), or no treatment (n = 6). A global proteomics analysis by 2D gel electrophoresis and mass spectrometry (MS) is then performed to identify proteins that are regulated after interference with RAS. Results: Three proteins are identified to show significant modulation of expression 60 kDa heat shock protein (downregulated), protein disulfide isomerase A3 (downregulated), and inorganic pyrophosphatase (upregulated). Conclusion: Three proteins with no previously known links to esophageal RAS, but with possible relevance for the development of esophageal adenocarcinoma (EAC) are detected. Altered expression by interference with the RAS suggests an involvement of angiotensin II in the development of EAC in BE. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 2. |
- Brinkmalm, Gunnar, et al.
(författare)
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A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease.
- 2018
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Ingår i: Proteomics. Clinical applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF).Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope-labeled peptide standards.Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin-2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin were also significantly lowered in AD (p<0.05). The other investigated proteins, β2-microglobulin, cystatin C, amyloid precursor protein, lysozyme C, neurexin-2, neurexin-3, and neurocan core protein, were not significantly altered.PRM-MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders.
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| 3. |
- Häggmark, Anna, et al.
(författare)
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Neuroproteomic profiling of human body fluids
- 2016
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Ingår i: PROTEOMICS - Clinical Applications. - : Wiley-VCH Verlagsgesellschaft. - 1862-8346 .- 1862-8354. ; 10:4, s. 485-502
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Forskningsöversikt (refereegranskat)abstract
- Analysis of protein expression and abundance provides a possibility to extend the current knowledge on disease-associated processes and pathways. The human brain is a complex organ and dysfunction or damage can give rise to a variety of neurological diseases. Although many proteins potentially reflecting disease progress are originating from brain, the scarce availability of human tissue material has lead to utilization of body fluids such as cerebrospinal fluid and blood in disease-related research. Within the most common neurological disorders, much effort has been spent on studying the role of a few hallmark proteins in disease pathogenesis but despite extensive investigation, the signatures they provide seem insufficient to fully understand and predict disease progress. In order to expand the view the field of neuroproteomics has lately emerged alongside developing technologies, such as affinity proteomics and mass spectrometry, for multiplexed and high-throughput protein profiling. Here, we provide an overview of how such technologies have been applied to study neurological disease and we also discuss some important considerations concerning discovery of disease-associated profiles.
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| 4. |
- Osman, Abdimajid, et al.
(författare)
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Peculiarities of studying the effects of pathogen reduction technologies on platelets
- 2016
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Ingår i: PROTEOMICS - Clinical Applications. - : WILEY-V C H VERLAG GMBH. - 1862-8346 .- 1862-8354. ; 10:8, s. 805-815
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Forskningsöversikt (refereegranskat)abstract
- The transfusion of platelet concentrates (PCs) is mainly used for treatment of thrombocytopenic, trauma or surgery patients. The integrity and safety of these platelet preparations, however, is compromised by the presence of pathogens, such as viruses, bacteria and parasites. The transfer of allogeneic donor leukocytes contaminating PCs can also potentially cause adverse reactions in recipients. These considerations prompted the development and implementation of pathogen reduction technologies (PRT), which are based on chemically induced cross-linking and inactivation of nucleic acids. While the incumbent PRT may provide some protection against transfusion-transmitted infections, they are ineffective against infectious prions and may not inactivate other emerging pathogens. In addition, the safety of PRT concerning platelet viability and function has been questioned in several reports. Recent studies suggest that PRT, such as Intercept, may adversely affect the messenger RNA (mRNA) and microRNA content of platelets, as well as their functional integrity, which may compromise the clinical benefits of PRT. Here, we will discuss about the peculiarities of studying the effects of PRT on platelets, which will need to be taken into account in future studies aimed to characterize further, and polish, the rugged side of this otherwise useful and potentially important approach in transfusion medicine.
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| 5. |
- Qundos, Ulrika, et al.
(författare)
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Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients
- 2016
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Ingår i: PROTEOMICS - Clinical Applications. - : Wiley-Blackwell. - 1862-8346 .- 1862-8354. ; 10:6, s. 681-690
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. Experimental design: Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population-based studies. Results: Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti-AMFR antibody selectivity was conducted using high-density peptide and protein arrays, and Western blotting. Conclusions and clinical relevance: Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis.
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| 6. |
- Remnestål, Julia, et al.
(författare)
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CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease
- 2016
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Ingår i: PROTEOMICS - Clinical Applications. - : Wiley-VCH Verlagsgesellschaft. - 1862-8346 .- 1862-8354. ; 10:12, s. 1242-1253
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study is part of a larger effort aiming to expand the knowledge of brain-enriched proteins in human cerebrospinal fluid (CSF) and to provide novel insight into the relation between such proteins and different neurodegenerative diseases. Experimental design: Here 280 brain-enriched proteins in CSF from patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are profiled. In total, 441 human samples of ventricular CSF collected post mortem and lumbar CSF collected ante mortem are analyzed using 376 antibodies in a suspension bead array setup, utilizing a direct labelling approach. Results: Among several proteins displaying differentiated profiles between sample groups, we focus here on two synaptic proteins, neuromodulin (GAP43) and neurogranin (NRGN). They are both found at elevated levels in CSF from AD patients in two independent cohorts, providing disease-associated profiles in addition to verifying and strengthening previously observed patterns. Increased levels are also observed for patients for whom the AD diagnosis was not established at the time of sampling. Conclusions and clinical relevance: These findings indicate that analyzing the brain-enriched proteins in CSF is of particular interest to increase the understanding of the CSF proteome and its relation to neurodegenerative disorders. In addition, this study lends support to the notion that measurements of these synaptic proteins could potentially be of great relevance in future diagnostic tests for AD.
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| 7. |
- Sahebekhtiari, Navid, et al.
(författare)
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Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity—A Study on Rare BMI-Discordant Monozygotic Twin Pairs
- 2019
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Ingår i: Proteomics - Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study is to elucidate the effect of excess body weight and liver fat on the plasma proteome without interference from genetic variation. Experimental Design: The effect of excess body weight is assessed in young, healthy monozygotic twins from pairs discordant for body mass index (intrapair difference (Δ) in BMI > 3 kg m −2 , n = 26) with untargeted LC-MS proteomics quantification. The effect of liver fat is interrogated via subgroup analysis of the BMI-discordant twin cohort: liver fat discordant pairs (Δliver fat > 2%, n = 12) and liver fat concordant pairs (Δliver fat < 2%, n = 14), measured by magnetic resonance spectroscopy. Results: Seventy-five proteins are differentially expressed, with significant enrichment for complement and inflammatory response pathways in the heavier co-twins. The complement dysregulation is found in obesity in both the liver fat subgroups. The complement and inflammatory proteins are significantly associated with adiposity measures, insulin resistance and impaired lipids. Conclusions and Clinical Relevance: The early pathophysiological mechanisms in obesity are incompletely understood. It is shown that aberrant complement regulation in plasma is present in very early stages of clinically healthy obese persons, independently of liver fat and in the absence of genetic variation that typically confounds human studies.
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| 8. |
- Sandin, Marianne, et al.
(författare)
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Is label-free LC-MS/MS ready for biomarker discovery?
- 2015
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Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 9:3-4, s. 289-294
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Tidskriftsartikel (refereegranskat)abstract
- Label-free LC-MS methods are attractive for high-throughput quantitative proteomics, as the sample processing is straightforward and can be scaled to a large number of samples. Label-free methods therefore facilitate biomarker discovery in studies involving dozens of clinical samples. However, despite the increased popularity of label-free workflows, there is a hesitance in the research community to use it in clinical proteomics studies. Therefore, we here discuss pros and cons of label free LC-MS/MS for biomarker discovery, and delineate the main prerequisites for its successful employment. Furthermore, we cite studies where label-free LC-MS/MS was successfully used to identify novel biomarkers, and foresee an increased acceptance of label-free techniques by the proteomics community in the near future. This article is protected by copyright. All rights reserved.
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| 9. |
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| 10. |
- Sjödin, Simon, et al.
(författare)
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Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer's Disease and Parkinsonian Disorders
- 2017
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Ingår i: Proteomics - Clinical Applications. - : Wiley. - 1862-8346 .- 1862-8354. ; 11:11-12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Dysfunctional proteostasis, with decreased protein degradation and an accumulation of ubiquitin into aggregated protein inclusions, is a feature of neurodegenerative diseases. Identifying new potential biomarkers in cerebrospinal fluid (CSF) reflecting this process could contribute important information on pathophysiology. Experimental design: A developed method combining SPE and PRM-MS is employed to monitor the concentration of ubiquitin in CSF from subjects with Alzheimer's disease (AD), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). Four independent cross-sectional studies are conducted, studies 1–4, including controls (n = 86) and participants with AD (n = 60), PD (n = 15), and PSP (n = 11). Results: The method shows a repeatability and intermediate precision not exceeding 6.1 and 7.9%, respectively. The determined LOD is 0.1 nm and the LOQ range between 0.625 and 80 nm. The CSF ubiquitin concentration is 1.2–1.5-fold higher in AD patients compared with controls in the three independent AD-control studies (Study 1, p < 0.001; Study 2, p < 0.001; and Study 3, p = 0.003). In the fourth study, there is no difference in PD or PSP, compared to controls. Conclusion and clinical relevance: CSF ubiquitin may reflect dysfunctional proteostasis in AD. The described method can be used for further exploration of ubiquitin as a potential biomarker in neurodegenerative diseases.
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