Search results for "target"
showing 10 items of 1196 documents
MetProc: Separating Measurement Artifacts from True Metabolites in an Untargeted Metabolomics Experiment
2019
High-throughput metabolomics using liquid chromatography and mass spectrometry (LC/MS) provides a useful method to identify biomarkers of disease and explore biological systems. However, the majority of metabolic features detected from untargeted metabolomics experiments have unknown ion signatures, making it critical that data should be thoroughly quality controlled to avoid analyzing false signals. Here, we present a postalignment method relying on intermittent pooled study samples to separate genuine metabolic features from potential measurement artifacts. We apply the method to lipid metabolite data from the PREDIMED (PREvención con DIeta MEDi-terránea) study to demonstrate clear remova…
The endoplasmic reticulum unfolded protein response in neurodegenerative disorders and its potential therapeutic significance
2017
In eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR) that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death. ER dysfunctions are involved and contribute to neuronal degeneration in several human diseases, including Al…
Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts
2020
Autophagy (cellular self-consumption) is a crucial adaptation mechanism during cellular stress conditions. This study aimed to examine how this important process is regulated in human periodontal ligament (PDL) fibroblasts by mechanical and inflammatory stress conditions and whether the mammalian target of rapamycin (mTOR) signaling pathway is involved. Autophagy was quantified by flow cytometry. Qualitative protein phosphorylation profiling of the mTOR pathway was carried out. Effects of mTOR regulation were assessed by quantification of important synthesis product collagen 1, cell proliferation and cell death with real-time PCR and flow cytometry. Autophagy as a response to mechanical or …
Self-packed core shell nano liquid chromatography columns and silica-based monolithic trap columns for targeted proteomics.
2016
Self-preparation of nano liquid chromatography (nLC) columns has advantages regarding cost and flexibility. For targeted proteomics, we evaluated several approaches for particle-packing nLC columns and manufacturing fritless silica-based monolithic trap columns (50μm inner diameter). Our preferred approach for nLC column preparation was to magnetically stir Accucore core shell particles (C18 stationary phase) in ACN/water (80/20, v/v) suspensions during pressure-driven filling of polymer-fritted standard fused silica capillaries. The columns were ready for use about one hour after preparation had begun. They had comparable peak capacities (peptides) to commercial columns, and satisfactory w…
Is proteomics of value in cardiovascular risk assessment?
2019
Purpose of review To briefly summarize recently published evidence in the field of cardiovascular proteomics, focusing on its ability to improve cardiovascular risk stratification and critically discussing still open and burning issues and future perspectives of proteomics research. Recent findings Several epidemiological studies have demonstrated an improvement in cardiovascular risk prediction beyond traditional risk factors by adding novel biomarkers, identified by both discovery and targeted proteomics. However, only a moderate improvement in risk discrimination over clinical variables was observed. Moreover, despite different outcomes there was also a strong overlap of identified candi…
Multi-omics approaches to improve malaria therapy.
2021
Malaria contributes to the most widespread infectious diseases worldwide. Even though current drugs are commercially available, the ever-increasing drug resistance problem by malaria parasites poses new challenges in malaria therapy. Hence, searching for efficient therapeutic strategies is of high priority in malaria control. In recent years, multi-omics technologies have been extensively applied to provide a more holistic view of functional principles and dynamics of biological mechanisms. We briefly review multi-omics technologies and focus on recent malaria progress conducted with the help of various omics methods. Then, we present up-to-date advances for multi-omics approaches in malari…
Data for the identification of proteins and post-translational modifications of proteins associated to histones H3 and H4 in S. cerevisiae, using tan…
2016
Tandem affinity purification method (TAP) allows the efficient purification of native protein complexes which incorporate a target protein fused with the TAP tag. Purified multiprotein complexes can then be subjected to diverse types of proteomic analyses. Here we describe the data acquired after applying the TAP strategy on histones H3 and H4 coupled with mass spectrometry to identify associated proteins and protein post-translational modifications in the budding yeast, Saccharomyces cerevisiae. The mass spectrometry dataset described here consists of 14 files generated from four different analyses in a 5600 Triple TOF (Sciex) by information‐dependent acquisition (IDA) LC–MS/MS. The above …
Potential treatment strategy for the rare osimertinib resistant mutation EGFR L718Q
2020
Epidermal growth factor receptor (EGFR) L718Q is a rare resistant mutation which independently leads to third-generation tyrosine kinase inhibitor (TKI) resistance. Although a few studies have examined its resistance mechanisms, no effective treatment strategy has yet been proposed for patients with this mutation. Here, we report an effective treatment strategy for the rare EGFR L718Q mutation for the first time. A 44-year-old Chinese male patient initially presented with the sensitizing EGFR L858R mutation, and the progression-free survival (PFS) time after initial icotinib treatment was 9 months. When the progression of the disease (PD) and the EGFR T790M mutation were identified, he did …
Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach
2018
Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This netw…
PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells
2020
ObjectiveCancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy.DesignA collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional…