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Clinical Proteomics

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https://www.readbyqxmd.com/read/29453042/evaluation-of-the-anti-hypertensive-effect-of-tengfu-jiangya-tablet-by-combination-of-uplc-q-exactive-ms-based-metabolomics-and-itraq-based-proteomics-technology
#1
Yanpeng Tian, Feng Jiang, Yunlun Li, Haiqiang Jiang, Yanjun Chu, Lijuan Zhu, Weixing Guo
OBJECTIVE: Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine formulation composed of Uncaria rhynchophylla and Semen raphani. It is a hospital preparation that is widely used in clinics for treating hypertension. A previous metabolomics study reported that TJT exerted a protective effect on hypertension by restoring impaired NO production, ameliorating the inflammatory state, and vascular remodeling. A clinical proteomics study also revealed five key target proteins during TJT intervention...
February 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29452276/application-of-targeted-mass-spectrometry-in-bottom-up-proteomics-for-systems-biology-research
#2
Nathan P Manes, Aleksandra Nita-Lazar
The enormous diversity of proteoforms produces tremendous complexity within cellular proteomes, facilitates intricate networks of molecular interactions, and constitutes a formidable analytical challenge for biomedical researchers. Currently, quantitative whole-proteome profiling often relies on non-targeted liquid chromatography-mass spectrometry (LC-MS), which samples proteoforms broadly, but can suffer from lower accuracy, sensitivity, and reproducibility compared with targeted LC-MS. Recent advances in bottom-up proteomics using targeted LC-MS have enabled previously unachievable identification and quantification of target proteins and posttranslational modifications within complex samples...
February 13, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29451788/a-systematic-evaluation-of-the-use-of-human-plasma-and-serum-for-mass-spectrometry-based-shotgun-proteomics
#3
Jiayi Lan, Antonio Núñez Galindo, James Doecke, Christopher Fowler, Ralph N Martins, Stephanie R Rainey-Smith, Ornella Cominetti, Loïc Dayon
Over the last two decades, EDTA-plasma has been used as the preferred sample matrix for human blood proteomic profiling. Serum has also been employed widely. Only a few studies have assessed the difference and relevance of the proteome profiles obtained from plasma samples, such as EDTA-plasma or lithium-heparin-plasma, and serum. A more complete evaluation of the use of EDTA-plasma, heparin-plasma, and serum would greatly expand the comprehensiveness of shotgun proteomics of blood samples. In this study, we evaluated the use of heparin-plasma with respect to EDTA-plasma and serum to profile blood proteomes using a scalable automated proteomic pipeline (ASAP2)...
February 16, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29451391/the-future-of-lc-ms-for-pharmaceutical-analysis-an-interview-with-jun-qu
#4
Jun Qu
Jun Qu speaks to Sankeetha Nadarajah, Editor of Bioanalysis: Jun Qu is the group leader of the proteomics and pharmaceutical analysis lab of SUNY-Buffalo (NY, USA) and a Professor in the Department of Pharmaceutical Sciences. His research is focused on the study of Clinical and Pharmaceutical Proteomics and Pharmaceutical Analysis using LC-MS-based strategies. His research programs include high-resolution and large-scale expression profiling of pathological proteomes, for the discovery of novel disease/therapeutics biomarkers using gel-free proteomic methods; sensitive identification, localization and quantification of post-translational modifications in tissue proteomes such as these in myocardium, using novel anti-PTM affinity capture and alternating Collision-induced dissociation/Electron transfer dissociation to obtain abundant PTM information; targeted investigation of marker proteins that are of high interests for clinical and pharmaceutical study, using highly sensitive nano-LC/SRM-based methods; and highly sensitive and accurate investigation of the PK of biotherapeutics using LC-MS...
February 16, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29449793/clinical-proteomic-analysis-of-scrub-typhus-infection
#5
Edmond Changkyun Park, Sang-Yeop Lee, Sung Ho Yun, Chi-Won Choi, Hayoung Lee, Hyun Seok Song, Sangmi Jun, Gun-Hwa Kim, Chang-Seop Lee, Seung Il Kim
Background: Scrub typhus is an acute and febrile infectious disease caused by the Gram-negative α-proteobacterium Orientia tsutsugamushi from the family Rickettsiaceae that is widely distributed in Northern, Southern and Eastern Asia. In the present study, we analysed the serum proteome of scrub typhus patients to investigate specific clinical protein patterns in an attempt to explain pathophysiology and discover potential biomarkers of infection. Methods: Serum samples were collected from three patients (before and after treatment with antibiotics) and three healthy subjects...
2018: Clinical Proteomics
https://www.readbyqxmd.com/read/29449571/an-in-silico-argument-for-mitochondrial-microrna-as-a-determinant-of-primary-non-function-in-liver-transplantation
#6
Shirin Elizabeth Khorsandi, Siamak Salehi, Miriam Cortes, Hector Vilca-Melendez, Krishna Menon, Parthi Srinivasan, Andreas Prachalias, Wayel Jassem, Nigel Heaton
Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449460/pfn2-and-gamt-as-common-molecular-determinants-of-axonal-charcot-marie-tooth-disease
#7
Manisha Juneja, Abdelkrim Azmi, Jonathan Baets, Andreas Roos, Matthew J Jennings, Paola Saveri, Chiara Pisciotta, Nathalie Bernard-Marissal, Bernard L Schneider, Catherine Verfaillie, Roman Chrast, Pavel Seeman, Angelika F Hahn, Peter de Jonghe, Stuart Maudsley, Rita Horvath, Davide Pareyson, Vincent Timmerman
BACKGROUND: Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes. METHODS: A proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins...
February 15, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29448998/cardiac-amyloidosis-from-clinical-suspicion-to-morphological-diagnosis
#8
REVIEW
Pavla Flodrova, Patrik Flodr, Tomas Pika, Jiri Vymetal, Dusan Holub, Petr Dzubak, Marian Hajduch, Vlastimil Scudla
Amyloidosis is a heterogeneous group of diseases characterised by extracellular accumulation of amyloid in various tissues and organs of the body, leading to alteration and destruction of tissues. Heart involvement is the most important prognostic factor in patients with systemic amyloidosis and the diagnosis and typing of amyloid must be made properly. The clinical picture shows congestive heart failure with predominant right-sided heart failure symptoms in fully developed disease, various types of arrhythmias and characteristic electrocardiography and echocardiography findings...
February 12, 2018: Pathology
https://www.readbyqxmd.com/read/29448056/proteomic-analysis-of-first-trimester-maternal-serum-to-identify-candidate-biomarkers-potentially-predictive-of-spontaneous-preterm-birth
#9
Arlene M D'Silva, Jon A Hyett, Jens R Coorssen
Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29446914/simultaneous-detection-of-human-c-terminal-p53-isoforms-by-single-template-molecularly-imprinted-polymers-mips-coupled-with-liquid-chromatography-tandem-mass-spectrometry-lc-ms-ms-based-targeted-proteomics
#10
Wenting Jiang, Liang Liu, Yun Chen
Abnormal expression of C-terminal p53 isoforms α, β, and γ can cause the development of cancers including breast cancer. To date, much evidence has demonstrated that these isoforms can differentially regulate target genes and modulate their expression. Thus, quantification of individual isoforms may help to link clinical outcome to p53 status and to improve cancer patient treatment. However, there are few studies on accurate determination of p53 isoforms, probably due to sequence homology of these isoforms and also their low abundance...
February 15, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29446379/astroglial-kir4-1-in-the-lateral-habenula-drives-neuronal-bursts-in-depression
#11
Yihui Cui, Yan Yang, Zheyi Ni, Yiyan Dong, Guohong Cai, Alexandre Foncelle, Shuangshuang Ma, Kangning Sang, Siyang Tang, Yuezhou Li, Ying Shen, Hugues Berry, Shengxi Wu, Hailan Hu
Enhanced bursting activity of neurons in the lateral habenula (LHb) is essential in driving depression-like behaviours, but the cause of this increase has been unknown. Here, using a high-throughput quantitative proteomic screen, we show that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on astrocytic membrane processes that wrap tightly around the neuronal soma. Electrophysiology and modelling data show that the level of Kir4...
February 14, 2018: Nature
https://www.readbyqxmd.com/read/29440177/ponatinib-shows-potent-antitumor-activity-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-sccoht-through-multi-kinase-inhibition
#12
Jessica D Lang, William P D Hendricks, Krystal A Orlando, Hongwei Yin, Jeffrey Kiefer, Pilar Ramos, Ritin Sharma, Patrick Pirrotte, Elizabeth A Raupach, Chris Sereduk, Nanyun Tang, Winnie S Liang, Megan Washington, Salvatore J Facista, Victoria L Zismann, Emily M Cousins, Michael B Major, Yemin Wang, Anthony N Karnezis, Aleksandar Sekulic, Ralf Hass, Barbara C Vanderhyden, Praveen Nair, Bernard E Weissman, David G Huntsman, Jeffrey M Trent
PURPOSE: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive ovarian cancer in young women that is universally driven by loss of the SWI/SNF ATPase subunits SMARCA4 and SMARCA2. A great need exists for effective targeted therapies for SCCOHT. EXPERIMENTAL DESIGN: To identify underlying therapeutic vulnerabilities in SCCOHT, we conducted high-throughput siRNA and drug screens. Complementary proteomics approaches profiled kinases inhibited by ponatinib...
February 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29438379/advancing-the-immunoaffinity-platform-affirm-to-targeted-measurements-of-proteins-in-serum-in-the-pg-ml-range
#13
Anna Säll, Daniel Corbee, Sara Vikström, Filip Ottosson, Helena Persson, Sofia Waldemarson
There is a great need for targeted protein assays with the capacity of sensitive measurements in complex samples such as plasma or serum, not the least for clinical purposes. Proteomics keeps generating hundreds of biomarker candidates that need to be transferred towards true clinical application through targeted verification studies and towards clinically applicable analysis formats. The immunoaffinity assay AFFIRM (AFFInity sRM) combines the sensitivity of recombinant single chain antibodies (scFv) for targeted protein enrichment with a specific mass spectrometry readout through selected reaction monitoring (SRM) in an automated workflow...
2018: PloS One
https://www.readbyqxmd.com/read/29437671/pharmacological-tlr4-antagonism-using-topical-resatorvid-blocks-solar-uv-induced-skin-tumorigenesis-in-skh-1-mice
#14
Karen Blohm-Mangone, Nichole B Burkett, Shekha Tahsin, Paul B Myrdal, Alhassan Aodah, Brenda Ho, Jaroslav Janda, Michelle McComas, Kathylynn Saboda, Denise J Roe, Zigang Dong, Ann M Bode, Emanuel F Petricoin, Valerie S Calvert, Clara Curiel-Lewandrowski, David S Alberts, Georg T Wondrak, Sally E Dickinson
An urgent need exists for the development of more efficacious molecular strategies targeting non-melanoma skin cancer (NMSC), the most common malignancy worldwide. Inflammatory signaling downstream of Toll-like receptor 4 (TLR4) has been implicated in several forms of tumorigenesis, yet its role in solar UV-induced skin carcinogenesis remains undefined. We have previously shown in keratinocyte cell culture and SKH-1 mouse epidermis that topical application of the specific TLR4 antagonist resatorvid (TAK-242) blocks acute UV-induced AP-1 and NF-κB signaling, associated with downregulation of inflammatory mediators and MAP Kinase phosphorylation...
February 1, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29435161/nonlinear-mixed-effects-dose-response-modeling-in-high-throughput-drug-screens-application-to-melanoma-cell-line-analysis
#15
Kuan-Fu Ding, Emanuel F Petricoin, Darren Finlay, Hongwei Yin, William P D Hendricks, Chris Sereduk, Jeffrey Kiefer, Aleksandar Sekulic, Patricia M LoRusso, Kristiina Vuori, Jeffrey M Trent, Nicholas J Schork
Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC50). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29431584/horizon-scanning-how-will-metabolomics-applications-transform-food-science-bioengineering-and-medical-innovation-in-the-current-era-of-foodomics
#16
Mustafa Bayram, Çağlar Gökırmaklı
Food and engineering sciences have tended to neglect the importance of human nutrition sciences and clinical study of new molecules discovered by food engineering community, and vice versa. Yet, the value of systems thinking and use of omics technologies in food engineering are rapidly emerging. Foodomics is a new concept and practice to bring about "precision nutrition" and integrative bioengineering studies of food composition, quality, and safety, and applications to improve health of humans, animals, and other living organisms on the planet...
February 12, 2018: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/29427919/the-building-blocks-of-successful-translation-of-proteomics-to-the-clinic
#17
REVIEW
Paul Kearney, J Jay Boniface, Nathan D Price, Leroy Hood
Recently, the first two multiplexed tests using selective reaction monitoring (SRM-MS) mass spectrometry have entered clinical practice. Despite different areas of indication, risk stratification in lung cancer and preterm birth, they share multiple steps in their development strategies. Here we review these strategies and their implications for successful translation of biomarkers to clinical practice. We believe that the identification of blood protein panels for the identification of disease phenotypes is now a reproducible and standard (albeit complex) process...
February 6, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29427020/-autoimmunity-and-glaucoma
#18
REVIEW
K Bell, S Funke, F H Grus
In addition to the clinically most relevant risk factor for glaucoma, i.e., elevated intraocular pressure (IOP), there are other factors with high relevance for the disease. Changes in the autoimmune component of the immune system are of particular importance. Clinical studies have demonstrated alterations in different autoantibodies in glaucoma patients compared to healthy controls, some of which increase in abundance/have a raised titer, but also some which have a reduced titer. These changes have a distinct potential-not only as a tool for early glaucoma detection, but also as a therapeutic option due to the documented neuroprotective effects of some of these antibodies...
February 9, 2018: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/29425736/targeted-proteomics-analyses-of-phosphorylation-dependent-signalling-networks
#19
Sara L Banerjee, Ugo Dionne, Jean-Philippe Lambert, Nicolas Bisson
Protein phosphorylation often regulates interactions between components of signalling networks. Its tight regulation by opposing actions of kinases and phosphatases contribute to making this modification key in controlling the dynamic architecture of phosphorylation-dependent networks. The introduction in cell signalling research of long-standing targeted proteomics approaches such as selected reaction monitoring (SRM) combined with the development of state-of-the-art methods such as parallel reaction monitoring (PRM) and data-independent analysis (DIA), have allowed delineating temporal quantitative profiles of interactions networks...
February 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29421973/multimodal-characterization-of-the-late-effects-of-tbi-letbi-a-methodological-overview-of-the-letbi-project
#20
Brian L Edlow, C Dirk Keene, Daniel Perl, Diego Iacono, Rebecca Folkerth, William Stewart, Christine L MacDonald, Jean Augustinack, Ramon Diaz-Arrastia, Camilo Estrada, Elissa Flannery, Wayne Gordon, Tom Grabowski, Kelly Hansen, Jeanne Hoffman, Christopher Kroenke, Eric Larson, Patricia Lee, Azma Mareyam, Jennifer A McNab, Jeanne McPhee, Allison L Moreau, Anne Renz, KatieRose Richmire, Allison Stevens, Cheuk Y Tang, Lee S Tirrell, Emily Trittschuh, Andre van der Kouwe, Ani Varjabedian, Lawrence L Wald, Ona Wu, Anastasia Yendiki, Liza Young, Lilla Zollei, Bruce Fischl, Paul K Crane, Kristen Dams-O'Connor
Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's and Parkinson's disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood...
February 8, 2018: Journal of Neurotrauma
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