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Proteomics. Clinical Applications

Li Zhou, Ji Wen, Zhao Huang, Edouard C Nice, Canhua Huang, Haiyuan Zhang, Qifu Li
Liver cancer is a major global health problem being the sixth most common cancer and the third cause of cancer-related death, with HCC representing more than 90% of primary liver cancers. Mounting evidence suggests that, compared with their normal counterparts, many types of cancer cell have increased levels of ROS. Therefore, cancer cells need to combat high levels of ROS, especially at early stages of tumour development. Recent studies have revealed that ROS-mediated regulation of redox-sensitive proteins (redox sensors) is involved in the pathogenesis and/or progression of many human diseases, including cancer...
October 20, 2016: Proteomics. Clinical Applications
Christoph W Turck, Christian Webhofer, Markus Nussbaumer, Larysa Teplytska, Alon Chen, Giuseppina Maccarrone, Michaela D Filiou
PURPOSE: In this work we discuss how in vivo (15) N metabolic labeling in combination with mass spectrometry simultaneously provides information on protein expression and protein turnover. EXPERIMENTAL DESIGN: We metabolically labeled mice with the stable nitrogen isotope (15) N using a (15) N-enriched diet and analyzed (15) N-labeled vs. unlabeled ((14) N) brain tissue with LC-MS/MS. We then compared the (14) N vs.(15) N peptide isotopologue clusters of (14) N and (15) N-labeled Dihydropyrimidinase-related (DPYSL) proteins...
October 20, 2016: Proteomics. Clinical Applications
Ramanujam Saravanan, Muthuvel Bharathselvi, Aravind C Babu, Jyothirmay Biswas, Konerirajapuram N Sulochana
PURPOSE: Eales' disease (ED), an enigmatic inflammatory disease affects peripheral retinal veins and thereby vision, in males. This study was aimed at identifying and deciphering the role of a novel 88 kDa protein reported in the serum and vitreous of patients with ED. EXPERIMENTAL DESIGN: The purified 88 kDa protein was identified by UPLC coupled ESI-QTOF-MS. The identified proteins were quantified in the serum from 20 ED patients and controls (age and sex matched), respectively by ELISA...
October 14, 2016: Proteomics. Clinical Applications
Eva Brauers, Andreas Roos, Laxmikanth Kollipara, René P Zahedi, Alf Beckmann, Nilane Mohanadas, Hartmut Bauer, Martin Häusler, Stéphanie Thoma, Wolfram Kress, Jan Senderek, Joachim Weis
In the era of next generation sequencing, we are increasingly confronted with sequence variants of unknown significance. Here, we focus on three patients carrying the sequence variant G56S in Caveolin-3 who presented with mild to moderate necrotizing myopathy and on the result of a controversial recent large scale analyses revealing that G56S is present at a frequency of around 10 % in the African population. Therefore, aim of our combined investigations was to address this discrepancy by morphological and biochemical studies...
October 14, 2016: Proteomics. Clinical Applications
Moses Henderson, Brittany Rice, Andrea Sebastian, Patrick G Sullivan, Christina King, Renã A S Robinson, Tanea T Reed
PURPOSE: The aims of this work are to establish a time point to determine the most beneficial time to administer GCEE post incident to reduce oxidative damage and secondly, by using redox proteomics, to determine if GCEE can readily suppress 3-NT modification in TBI animals. EXPERIMENTAL DESIGN: By using a moderate traumatic brain injury model with Wistar rats, it is hypothesized that the role of 3 - NT formation as an intermediate will predict the involvement of protein nitration/nitrosation and oxidative damage in the brain...
October 14, 2016: Proteomics. Clinical Applications
Matthew B O'Rourke, Matthew P Padula
PURPOSE: MALDI IMS is principally used for cancer diagnostics. In our own experience with publishing IMS data, we have been requested to modify our protocols with respect to the areas of the tissue that are imaged in order to comply with the wider literature. In light of this, we have determined that current methodologies lack effective controls and can potentially introduce bias by only imaging specific areas of the targeted tissue EXPERIMENTAL DESIGN: A previously imaged sample was selected and then cropped in different ways to show the potential effect of only imaging targeted areas...
October 11, 2016: Proteomics. Clinical Applications
Samina Arshid, Muhammad Tahir, Belchor Fontes, Edna Frasson de Souza Montero, Mariana Souza Castro, Simone Sidoli, Peter Roepstorff, Wagner Fontes
In clinical conditions trauma is associated with high mortality and morbidity. Neutrophils play a key role in the development of multiple organ failure after trauma. To have a detailed understanding of the neutrophil activation at primary stages after trauma, neutrophils were isolated from control and surgical trauma rats in this study. Extracted proteins were analyzed using nano liquid chromatography coupled to tandem mass spectrometry. A total of 2924 rat neutrophil proteins were identified in our analysis, of which 393 were found differentially regulated between control and trauma groups...
September 27, 2016: Proteomics. Clinical Applications
Liqing Gu, Renã A S Robinson
Cysteine is a highly reactive amino acid and is subject to a variety of reversible post-translational modifications (PTMs), including nitrosylation, glutathionylation, palmitoylation, as well as formation of sulfenic acid and disulfides. These modifications are not only involved in normal biological activities, such as enzymatic catalysis, redox signaling and cellular homeostasis, but can also be the result of oxidative damage. Especially in aging and neurodegenerative diseases, oxidative stress leads to aberrant cysteine oxidations that affect protein structure and function leading to neurodegeneration as well as other detrimental effects...
September 26, 2016: Proteomics. Clinical Applications
Kin Chan, Clifford Shone, J Richard Hesp
PURPOSE: The focus of this study was to characterise the effect of clinically relevant stress inducing conditions on the production and composition of proinflammatory outer membrane vesicles (OMVs) produced from ST131 ExPEC clinical isolates. EXPERIMENTAL DESIGN: A label-free method (SINQ) was used to identify changes in the respective OMV proteomes following exposure of the ExPEC strains to antibiotics and low iron. Nanoparticle tracking analysis was used to quantify changes in abundance and size of OMVs produced by the gentamicin resistant (GenR) and sensitive (GenS) ExPEC strains...
September 26, 2016: Proteomics. Clinical Applications
Yuan Gao, Zhijun Cao, Xi Yang, Mohamed A Abdelmegeed, Jinchun Sun, Si Chen, Richard D Beger, Kelly Davis, William F Salminen, Byoung-Joon Song, Donna L Mendrick, Li-Rong Yu
Overdose of acetaminophen (APAP) is a major cause of acute liver failure. To identify pathways related to hepatotoxicity and potential biomarkers of liver injury, a proteomic approach of (16) O/(18) O labeling and 2D-LC-MS/MS was used to analyze liver tissues from rats at 6 and 24 h post-treatment with low (100 mg/kg) and high (1250 mg/kg) doses of APAP. The analysis revealed that molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner...
September 16, 2016: Proteomics. Clinical Applications
Caroline B Van Den Berg, Johannes J Duvekot, Coşkun Güzel, Stefan R Hansson, Thomas G DE Leeuw, Eric A P Steegers, Johannes Versendaal, Theo M Luider, Marcel P Stoop
PURPOSE: To investigate the cerebrospinal fluid proteome of patients with preeclampsia and normotensive pregnant women, in order to provide a better understanding of brain involvement in preeclampsia. EXPERIMENTAL DESIGN: 98 cerebrospinal fluid samples (43 women with preeclampsia and 55 normotensive controls) were analyzed by LC-MS/MS proteome profiling. Cerebrospinal fluid was obtained during the spinal puncture before Caesarean delivery. RESULTS: Eight proteins were higher abundant and 17 proteins were lower abundant in patients with preeclampsia...
September 11, 2016: Proteomics. Clinical Applications
Lucia Carboni, Thanh-Phuong Nguyen, Laura Caberlotto
PURPOSE: The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. EXPERIMENTAL DESIGN: Network analysis is performed integrating preexisting proteomic data from rodent models of depression...
September 10, 2016: Proteomics. Clinical Applications
Julia Remnestål, David Just, Nicholas Mitsios, Claudia Fredolini, Jan Mulder, Jochen M Schwenk, Mathias Uhlén, Kim Kultima, Martin Ingelsson, Lena Kilander, Lars Lannfelt, Per Svenningsson, Bengt Nellgård, Henrik Zetterberg, Kaj Blennow, Peter Nilsson, Anna Häggmark-Månberg
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...
September 8, 2016: Proteomics. Clinical Applications
Donatus O Onwuli, Laura Rigau-Roca, Chris Cawthorne, Pedro Beltran-Alvarez
PURPOSE: Arginine methylation (ArgMe) is one of the most ubiquitous post-translational modifications, and hundreds of proteins undergo ArgMe in e.g. brain. However, the scope of ArgMe in many tissues, including the heart, is currently under explored. Here, we aimed to 1) identify proteins undergoing ArgMe in human organs, and 2) expose the relevance of ArgMe in cardiac disease. EXPERIMENTAL DESIGN: We used publicly available proteomic data to search for ArgMe in 13 human tissues...
September 7, 2016: Proteomics. Clinical Applications
Pedro J Alcolea, Gabriel I L Tuñón, Ana Alonso, Francisco García-Tabares, Sergio Ciordia, María C Mena, Roseane N S Campos, Roque P Almeida, Vicente Larraga
PURPOSE: Leishmania chagasi is the causative agent of zoonotic visceral leishmaniasis in Brazil. Domestic and stray dogs are the main reservoirs. The life cycle of the parasite involves two stages. Promastigotes are extracellular and develop within the sand fly gut. Amastigotes survive inside the harsh environment of the phagolysosome of mammalian host phagocytes, which display the nitric oxide defense mechanism. Surprisingly, we were able to isolate promastigotes that are also resistant to NO...
September 7, 2016: Proteomics. Clinical Applications
Jinseong Jeon, Hyuck Jun Mok, Youngwoo Choi, Seung Chul Park, Hunho Jo, Jin Her, Jin-Kwan Han, Yoon-Keun Kim, Kwang Pyo Kim, Changill Ban
Extracellular vesicle (EV) has been reported to conduct critical pathophysiological functions as an emerging mode of communication in bacteria. Recently, Propionibacterium acnes, an anaerobic Gram-positive human commensal found in the skin and gastrointestinal tract, has drawn increasing attention as an underestimated pathogen in a variety of diseases. For the comprehensive understanding of P. acnes, here we report the isolation of P. acnes EVs for the first time and identification of 252 vesicular proteins with high confidence using triplicate LC-MS/MS analyses...
September 5, 2016: Proteomics. Clinical Applications
D Allan Butterfield, Tanea T Reed
Traumatic brain injury (TBI) is a spontaneous event in which sudden trauma and secondary injury cause brain damage. Symptoms of TBI can range from mild to severe depending on extent of injury. The outcome can span from complete patient recovery to permanent memory loss and neurological decline. Currently, there is no known cure for TBI; however, immediate medical attention after injury is most beneficial for patient recovery. It is a well-established concept that imbalances in the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and native antioxidant mechanisms have been shown to increase oxidative stress...
September 2, 2016: Proteomics. Clinical Applications
Kelly L Stauch, Lance M Villeneuve, Phillip R Purnell, Brendan M Ottemann, Katy Emanuel, Howard S Fox
PURPOSE: Mutations in PTEN-induced putative kinase 1 (Pink1), a mitochondrial serine/threonine kinase, cause a recessive inherited form of Parkinson's disease (PD). Pink1 deletion in rats results in a progressive PD-like phenotype, characterized by significant motor deficits starting at 4 months of age. Despite the evidence of mitochondrial dysfunction, the pathogenic mechanism underlying disease due to Pink1-deficiency remains obscure. EXPERIMENTAL DESIGN: Striatal synaptic mitochondria from 3-month-old Pink1-deficient rats were characterized using bioenergetic and mass spectroscopy (MS)-based proteomic analyses...
August 28, 2016: Proteomics. Clinical Applications
Jacques Riby, James Mobley, Jianqing Zhang, Paige M Bracci, Christine F Skibola
PURPOSE: The aim of this pilot study was to conduct a non-targeted exploratory proteomics profiling analysis on sera obtained from patients diagnosed with diffuse large B-cell lymphoma (DLBCL) with the goal of identifying disease-specific biomarkers. EXPERIMENTAL DESIGN: Sera from 87 participants (57 chemotherapy-naïve diffuse DLBCL patients, 30 controls frequency-matched by age group and World Health Organization (WHO) BMI categories) that were part of a large San Francisco Bay Area case-control study of non-Hodgkin lymphoma were analyzed by liquid chromatography combined with tandem mass spectrometry...
August 25, 2016: Proteomics. Clinical Applications
Pathrapol Lithanatudom, Duncan R Smith
A number of studies have used global protein profiling technologies on a range of patient samples to detect proteins that are differentially expressed in β-thalassemia/Hb E as an aid to understanding the physiopathology of this disease. Seven studies have identified a total of 111 unique, differentially expressed proteins. Seven proteins (prothrombin, alpha-1-antichymotrypsin, fibrinogen beta chain, hemoglobin beta, selenium-binding protein, microtubule-actin cross-linking factor and adenomatous polyposis coli protein 2) have been identified in two independent studies, while two proteins (carbonic anhydrase 1 and peroxiredoxin-2) have been identified in three independent studies...
August 11, 2016: Proteomics. Clinical Applications
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