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Clinical Proteomics

Wataru Kikuchi, Motoi Nishimura, Takahisa Kuga, Sachio Tsuchida, Tatsuya Saito, Mamoru Satoh, Kenta Noda, Yoshio Kodera, Takeshi Tomonaga, Fumio Nomura
BACKGROUND: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube...
2016: Clinical Proteomics
Leena Liljedahl, Maiken Højgaard Pedersen, Jenny Norlin, James N McGuire, Peter James
BACKGROUND: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances...
2016: Clinical Proteomics
Clementina Mesaros, Ian A Blair
Mass spectrometry-based proteomics methodology has become an important tool in elucidating some of the underlying mechanisms involved in cardiovascular disease. The present review provides details on selected important protein targets where highly selective and specific mass spectrometry-based approaches have led to important new findings and provided new mechanistic information. The role of six proteins involved in the etiology of cardiovascular disease (acetylated platelet cyclooxygenase-1, serum apolipoprotein A1, apolipoprotein C-III, serum C-reactive protein, serum high mobility group box-1 protein, insulin-like growth factor I) and their quantification has been discussed...
2016: Clinical Proteomics
Maria Kaisar, Leon F A van Dullemen, Marie-Laëtitia Thézénas, M Zeeshan Akhtar, Honglei Huang, Sandrine Rendel, Philip D Charles, Roman Fischer, Rutger J Ploeg, Benedikt M Kessler
BACKGROUND: The successful application of-omics technologies in the discovery of novel biomarkers and targets of therapeutic interventions is facilitated by large collections of well curated clinical samples stored in bio banks. Mining the plasma proteome holds promise to improve our understanding of disease mechanisms and may represent a source of biomarkers. However, a major confounding factor for defining disease-specific proteomic signatures in plasma is the variation in handling and processing of clinical samples leading to protein degradation...
2016: Clinical Proteomics
Allison B Chambliss, Daniel W Chan
Disease progression and drug response may vary significantly from patient to patient. Fortunately, the rapid development of high-throughput 'omics' technologies has allowed for the identification of potential biomarkers that may aid in the understanding of the heterogeneities in disease development and treatment outcomes. However, mechanistic gaps remain when the genome or the proteome are investigated independently in response to drug treatment. In this article, we discuss the current status of pharmacogenomics in precision medicine and highlight the needs for concordant analysis at the proteome and metabolome levels via the more recently-evolved fields of pharmacoproteomics, toxicoproteomics, and pharmacometabolomics...
2016: Clinical Proteomics
Miloslav Sanda, Julius Benicky, Jing Wu, Yiwen Wang, Kepher Makambi, Jaeil Ahn, Coleman I Smith, Peng Zhao, Lihua Zhang, Radoslav Goldman
BACKGROUND: Non-invasive monitoring of liver disease remains an important health issue. Liver secreted glycoproteins reflect pathophysiological states of the organ and represent a rational target for serologic monitoring. In this study, we describe sialylated O-glycoforms of liver-secreted hemopexin (HPX) and quantify them as a ratio of disialylated to monosialylated form (S-HPX). METHODS: We measured S-HPX in serum of participants of the HALT-C trial using a LC-MS/MS-MRM assay...
2016: Clinical Proteomics
Merry L Lindsey, Michael E Hall, Romain Harmancey, Yonggang Ma
Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of cardiac wound healing responses that involve stimulation of robust inflammation to clear necrotic myocytes and tissue debris and induction of extracellular matrix (ECM) protein synthesis to generate a scar. Proteomic strategies provide us with a means to index the ECM proteins expressed in the LV, quantify amounts, determine functions, and explore interactions. This review will focus on the efforts taken in the proteomics research field that have expanded our understanding of post-MI LV remodeling, concentrating on the strengths and limitations of different proteomic approaches to glean information that is specific to ECM turnover in the post-MI setting...
2016: Clinical Proteomics
Lisa H Cazares, Michael D Ward, Ernst E Brueggemann, Tara Kenny, Paul Demond, Christopher R Mahone, Karen A O Martins, Jonathan E Nuss, Trevor Glaros, Sina Bavari
BACKGROUND: Ebola virus like particles (EBOV VLPs, eVLPs), are produced by expressing the viral transmembrane glycoprotein (GP) and structural matrix protein VP40 in mammalian cells. When expressed, these proteins self-assemble and bud from 'host' cells displaying morphology similar to infectious virions. Several studies have shown that rodents and non-human primates vaccinated with eVLPs are protected from lethal EBOV challenge. The mucin-like domain of envelope glycoprotein GP1 serves as the major target for a productive humoral immune response...
2016: Clinical Proteomics
Ravi C Dwivedi, Mario Navarrete, Nora Choi, Victor Spicer, Claudio Rigatto, Rakesh C Arora, Oleg Krokhin, Julie Ho, John A Wilkins
BACKGROUND: The urinary proteome of patients undergoing cardiopulmonary bypass (CPB) may provide important insights into systemic and renal changes associated with the procedure. Such information may ultimately provide a basis to differentiate changes or properties associated with the development of acute kidney injury. While mass spectrometry (MS) analysis offers the potential for in-depth compositional analysis it is often limited in coverage and relative quantitation capacity. The aim of this study was to develop a process flow for the preparation and comparison of the intraoperative urinary proteome...
2016: Clinical Proteomics
Ana Konvalinka, Ihor Batruch, Tomas Tokar, Apostolos Dimitromanolakis, Shelby Reid, Xuewen Song, York Pei, Andrei P Drabovich, Eleftherios P Diamandis, Igor Jurisica, James W Scholey
BACKGROUND: Angiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo. METHODS: In this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients...
2016: Clinical Proteomics
Preeti Rawat, Shveta Bathla, Rubina Baithalu, Munna Lal Yadav, Sudarshan Kumar, Syed Azamal Ali, Anurag Tiwari, Masoud Lotfan, Jasmine Naru, Manoj Jena, Pradip Behere, Ashok K Balhara, Rajesh Vashisth, Inderjeet Singh, Ajay Dang, Jai K Kaushik, Tushar K Mohanty, Ashok K Mohanty
BACKGROUND: An early, reliable and noninvasive method of early pregnancy diagnosis is prerequisite for efficient reproductive management in dairy industry. The early detection of pregnancy also help in to reduce the calving interval and rebreeding time which is beneficial for industries as well as farmers. The aim of this work is to identify potential biomarker for pregnancy detection at earlier stages (16-25 days). To achieve this goal we performed DIGE and LFQ for identification of protein which has significant differential expression during pregnancy...
2016: Clinical Proteomics
Chunchao Zhang, Jinfeng Suo, Hiroyuki Katayama, Yue Wei, Guillermo Garcia-Manero, Samir Hanash
BACKGROUND: The refractory nature of many cancers remains the main health challenge over the past century. The epigenetic drug, decitabine (DAC), represents one of the most promising therapeutic agents in cancers particularly in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, its ambiguous anti-tumor mechanism and the unpredictable drug-resistant nature in some population compromise its application in cancer therapy. In crosstalk with DNA methylation, histone post-translational modifications (PTMs) are the key players in modulating the downstream epigenetic status of tumor suppressor genes...
2016: Clinical Proteomics
Gajanan Sathe, Sneha M Pinto, Nazia Syed, Vishalakshi Nanjappa, Hitendra S Solanki, Santosh Renuse, Sandip Chavan, Aafaque Ahmad Khan, Arun H Patil, Raja Sekhar Nirujogi, Bipin Nair, Premendu Prakash Mathur, T S Keshava Prasad, Harsha Gowda, Aditi Chatterjee
BACKGROUND: Curcumin, derived from the rhizome Curcuma longa, is a natural anti-cancer agent and has been shown to inhibit proliferation and survival of tumor cells. Although the anti-cancer effects of curcumin are well established, detailed understanding of the signaling pathways altered by curcumin is still lacking. In this study, we carried out SILAC-based quantitative proteomic analysis of a HNSCC cell line (CAL 27) to investigate tyrosine signaling in response to curcumin. RESULTS: Using high resolution Orbitrap Fusion Tribrid Fourier transform mass spectrometer, we identified 627 phosphotyrosine sites mapping to 359 proteins...
2016: Clinical Proteomics
Mitali Bhattacharjee, Lavanya Balakrishnan, Santosh Renuse, Jayshree Advani, Renu Goel, Gajanan Sathe, T S Keshava Prasad, Bipin Nair, Ramesh Jois, Subramanian Shankar, Akhilesh Pandey
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there are currently no definitive markers for early diagnosis of RA and for monitoring the progression of this disease, though some of the markers like anti CCP antibodies and anti vimentin antibodies are promising. We sought to catalogue the proteins present in the synovial fluid of patients with RA. It was done with the aim of identifying newer biomarkers, if any, that might prove promising in future...
2016: Clinical Proteomics
Ilijana Begcevic, Davor Brinc, Andrei P Drabovich, Ihor Batruch, Eleftherios P Diamandis
BACKGROUND: Cerebrospinal fluid (CSF) is a proximal fluid which communicates closely with brain tissue, contains numerous brain-derived proteins and thus represents a promising fluid for discovery of biomarkers of central nervous system (CNS) diseases. The main purpose of this study was to generate an extensive CSF proteome and define brain-related proteins identified in CSF, suitable for development of diagnostic assays. METHODS: Six non-pathological CSF samples from three female and three male individuals were selected for CSF analysis...
2016: Clinical Proteomics
Mohor Biplab Sengupta, Arunabha Chakrabarti, Suparna Saha, Debashis Mukhopadhyay
The dynamic field of neurosciences entails ever increasing search for molecular mechanisms of disease states, especially in the domain of neurodegenerative disorders. The previous century heralded the techniques in proteomics when indexing of the human proteomes relating to various disease conditions became important. Early stage research in certain diseases or pathological conditions requires a more holistic approach of first discovering the proteins of interest for the condition. Despite its limitations, proteomics is one of the most powerful techniques available to us today to dissect the molecular scenario in a particular disease situation...
2016: Clinical Proteomics
Aparna Verma, Kiran Ambatipudi
Bovine milk and its products (e.g. cheese, yoghurt) are an important part of human diet with beneficial effects for all ages. Although analyses of different milk components (e.g. proteins, lipids) pose huge challenges, the use of mass spectrometric (MS)-based techniques is steadily improving our understanding of the complexity of the biological traits that effect milk yield and its components to meet the global demand arising from population growth. In addition, different milk constituents have various applications in veterinary research and medicine, including early disease diagnosis...
2016: Clinical Proteomics
Yetrib Hathout, Haeri Seol, Meng Hsuan J Han, Aiping Zhang, Kristy J Brown, Eric P Hoffman
Assessments of disease progression and response to therapies in Duchenne muscular dystrophy (DMD) patients remain challenging. Current DMD patient assessments include complex physical tests and invasive procedures such as muscle biopsies, which are not suitable for young children. Defining alternative, less invasive and objective outcome measures to assess disease progression and response to therapy will aid drug development and clinical trials in DMD. In this review we highlight advances in development of non-invasive blood circulating biomarkers as a means to assess disease progression and response to therapies in DMD...
2016: Clinical Proteomics
Mashanipalya G Jagadeeshaprasad, Kedar B Batkulwar, Nishita N Meshram, Shalbha Tiwari, Arvind M Korwar, Ambika G Unnikrishnan, Mahesh J Kulkarni
BACKGROUND: N-1-(Deoxyfructosyl) valine (DFV) β-hemoglobin (β-Hb), commonly referred as HbA1c, is widely used diagnostic marker in diabetes, believed to provide glycemic status of preceding 90-120 days. However, the turnover of hemoglobin is about 120 days, the DFV-β-Hb, an early and reversible glycation product eventually may undergo irreversible advanced glycation modifications such as carboxymethylation or carboxyethylation. Hence quantification of N-1-(carboxymethyl) valine (CMV) and N-1-(carboxyethyl) valine (CEV) peptides of β-Hb would be useful in assessing actual glycemic status...
2016: Clinical Proteomics
Yeji Kim, Nathan Edwards, Catherine Fenselau
BACKGROUND: Extracellular vesicles (EV) are spherical membrane-bound vesicles with nano-scale diameters, which are shed to the extracellular region by most eukaryotic and prokaryotic cells. Bacterial EV are proposed to contribute to intercellular communication, bacterial survival and human pathogenesis as a novel secretion system. EV have been characterized from many Gram-negative species and, more recently, from several vegetative Gram-positive bacteria. Further characterization of EV and their molecular cargos will contribute to understanding bacterial physiology and to developing therapeutic approaches...
2016: Clinical Proteomics
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