Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(2)

Published: Feb. 1, 2024

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of cell origin and change functions phenotypes other cells. These features indicate strong biomarker therapeutic potential have generated broad interest, as evidenced by steady year-on-year increase in numbers scientific publications about EVs. Important advances been made EV metrology understanding applying biology. However, hurdles remain to realising EVs domains ranging from basic biology clinical applications due challenges nomenclature, separation non-vesicular extracellular particles, characterisation functional studies. To address opportunities this rapidly evolving field, International Society for Vesicles (ISEV) updates its 'Minimal Information Studies Vesicles', which was first published 2014 then 2018 MISEV2014 MISEV2018, respectively. The goal current document, MISEV2023, is provide researchers with an updated snapshot available approaches advantages limitations production, multiple sources, including culture, body fluids solid tissues. In addition presenting latest art principles research, document also covers advanced techniques that are currently expanding boundaries field. MISEV2023 includes new sections on release uptake a brief discussion vivo study Compiling feedback ISEV expert task forces more than 1000 researchers, conveys research facilitate robust discoveries move field forward even rapidly.

Language: Английский

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Applications of Tandem Mass Spectrometry (MS/MS) in Protein Analysis for Biomedical Research

Molecules, Journal Year: 2022, Volume and Issue: 27(8), P. 2411 - 2411

Published: April 8, 2022

Mass Spectrometry (MS) allows the analysis of proteins and peptides through a variety methods, such as Electrospray Ionization-Mass (ESI-MS) or Matrix-Assisted Laser Desorption (MALDI-MS). These methods allow identification mass protein peptide intact molecules peptide-mass fingerprinting generated upon enzymatic digestion. Tandem spectrometry (MS/MS) fragmentation to determine amino acid sequence (top-down middle-down proteomics) (bottom-up proteomics). Furthermore, tandem also post-translational modifications (PTMs) peptides. Here, we discuss application MS/MS in biomedical research, indicating specific examples for their PTMs relevant biomarkers diagnostic therapy.

Language: Английский

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Recent advances in proteomics and metabolomics in plants

Molecular Horticulture, Journal Year: 2022, Volume and Issue: 2(1)

Published: July 23, 2022

Over the past decade, systems biology and plant-omics have increasingly become main stream in plant research. New developments mass spectrometry bioinformatics tools, methodological schema to integrate multi-omics data leveraged recent advances proteomics metabolomics. These progresses are driving a rapid evolution field of research, greatly facilitating our understanding mechanistic aspects metabolisms interactions plants with their external environment. Here, we review MS-based metabolomics tools workflows special focus on applications research using several case studies related stress response, gene/protein function characterization, metabolic signaling pathways exploration, natural product discovery. We also present projection concerning future perspectives development including challenges for system biology. This is intended provide readers an overview how advanced MS technology, integrated application can be used advance

Language: Английский

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Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study

Gut, Journal Year: 2023, Volume and Issue: 72(11), P. 2051 - 2067

Published: July 17, 2023

Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead high-performance blood tests towards GC diagnosis prognosis. We attempted develop diagnostic prognostic models for based on plasma metabolic information.We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort 264 prospective cohort. Discovery verification phases were through machine learning Cox regression fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, developed model was validated both NPELDI-MS ultra-performance liquid chromatography-MS (UPLC-MS).We demonstrated high throughput, desirable reproducibility limited centre-specific effects PMFs NPELDI-MS. In cohort, we achieved performance with areas under curves (AUCs) 0.862-0.988 discovery (n=1157 5 centres) independent external dataset (n=787 another 2 centres), different PMFs, including neural network, ridge regression, lasso support vector random forest. Further, panel consisting 21 metabolites constructed identified AUCs 0.921-0.971 0.907-0.940 dataset, respectively. (n=264 centre), UPLC-MS applied detect validate panel, 0.855-0.918 0.856-0.916, Moreover, prognosis scoring system which can effectively predict survival patients.We GC, also contribute advanced analysis diseases, but not GC.

Language: Английский

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timsTOF HT Improves Protein Identification and Quantitative Reproducibility for Deep Unbiased Plasma Protein Biomarker Discovery

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(3), P. 929 - 938

Published: Jan. 15, 2024

Mass spectrometry (MS) is a valuable tool for plasma proteome profiling and disease biomarker discovery. However, wide-ranging protein concentrations, along with technical biological variabilities, present significant challenges deep reproducible quantitation. Here, we evaluated the qualitative quantitative performance of timsTOF HT Pro 2 mass spectrometers analysis neat (unfractionated) Proteograph-processed across wide range peptide loading masses liquid chromatography (LC) gradients. We observed up to 76% increase in total precursors identified >2-fold boost quantifiable (CV < 20%) compared 2. In an exploratory 20 late-stage lung cancer control samples, which were expected exhibit distinct proteomes, approximate 50% statistically (q 0.05) was Our data demonstrate superior identifying quantifying differences between biologically diverse allowing improved discovery large cohort studies. Moreover, researchers can leverage sets from this study optimize their chromatography–mass (LC–MS) workflows (ProteomeXchange identifier: PXD047854 PXD047839).

Language: Английский

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Proteomics of human biological fluids for biomarker discoveries: technical advances and recent applications

Expert Review of Proteomics, Journal Year: 2022, Volume and Issue: 19(2), P. 131 - 151

Published: Feb. 1, 2022

Biological fluids are routine samples for diagnostic testing and monitoring. Blood typically measured because of their moderate invasive collection high information content on health disease. Several body fluids, such as cerebrospinal fluid (CSF), also studied suited to specific pathologies. Over the last two decades, proteomics has quested identify protein biomarkers but with limited success. Recent technologies refined pipelines have accelerated profiling human biological fluids.We review proteomic identification biomarkers. These based antibodies/aptamers arrays or mass spectrometry (MS), new ones emerging. Advances in scalability throughput allowed better design studies cope sample size that until now prevailed due technological constraints. With these enablers, plasma/serum, CSF, saliva, tears, urine, milk proteomes been further profiled; we provide a non-exhaustive picture some recent highlights (mainly covering literature from 5 years Scopus database) using MS-based proteomics.While shadow genomics years, tools methodologies reached certain maturity. They discover innovative robust biofluid

Language: Английский

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Development of Nucleic‐Acid‐Based Electrochemical Biosensors for Clinical Applications

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(50)

Published: Sept. 30, 2022

Nucleic acids are remarkable molecules. In addition to Watson-Crick base pairing, the different structural motifs of these molecules can bind non-nucleic acid targets or catalyze chemical reactions. Additionally, nucleic easily modified with functional groups. These properties make acids, particularly DNA, ideally suited for use in electrochemical biosensors, both as biorecognition elements and redox reporter probes. this Minireview, we will review historical evolution probes biosensors. We then specific examples nucleic-acid-based biosensors that have been evaluated clinical areas infectious disease, cancer, cardiovascular health.

Language: Английский

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Machine Learning Assisted Simultaneous Structural Profiling of Differently Charged Proteins in a Mycobacterium smegmatis Porin A (MspA) Electroosmotic Trap

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(2), P. 757 - 768

Published: Jan. 7, 2022

The nanopore is emerging as a means of single-molecule protein sensing. However, proteins demonstrate different charge properties, which complicates the design sensor that can achieve simultaneous sensing differently charged proteins. In this work, we introduce an asymmetric electrolyte buffer combined with Mycobacterium smegmatis porin A (MspA) to form electroosmotic flow (EOF) trap. Apo- and holo-myoglobin, differ in only single heme, be fully distinguished by method. Direct discrimination lysozyme, apo/holo-myoglobin, ACTR/NCBD complex, are basic, neutral, acidic proteins, respectively, was simultaneously achieved MspA EOF To automate event classification, multiple features were extracted build machine learning model, 99.9% accuracy achieved. demonstrated method also applied identify molecules α-lactalbumin β-lactoglobulin directly from whey powder. This protein-sensing strategy useful direct recognition mixture, suggesting its prospective use rapid sensitive detection biomarkers or real-time structural analysis.

Language: Английский

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Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification

Journal of Internal Medicine, Journal Year: 2023, Volume and Issue: 294(4), P. 378 - 396

Published: April 24, 2023

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors comprise common noncommunicable diseases, including allergies, cardiovascular disease, psychiatric metabolic disorders. More than 25% Europeans suffer from complex together these account for 70% all deaths. The use genomic, molecular, or imaging data to develop accurate diagnostic tools treatment recommendations preventive strategies, disease prognosis prediction, is an important step toward precision medicine. However, medicine associated with several challenges. There significant heterogeneity between patients specific disease-both regards symptoms underlying causal mechanisms-and the number genetic nongenetic risk often high. Here, we summarize approaches highlight current breakthroughs as well We conclude that genomic-based has been used mainly highly penetrant monogenic forms, such cardiomyopathies. most diseases-including disorders allergies-available polygenic scores more probabilistic deterministic have not yet validated clinical utility. subclassifying into discrete homogenous subtypes based on molecular phenotypic promising strategy improving diagnosis, treatment, prevention, prognosis. availability high-throughput technologies, large collections health novel data-driven approaches, offers promise improved individual through

Language: Английский

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Clinical Translation of Targeted Protein Degraders

Clinical Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 114(3), P. 558 - 568

Published: July 3, 2023

Targeted protein degradation (TPD) has emerged as a potentially transformational therapeutic modality with considerable promise. Molecular glue degraders remodel the surface of E3 ligases inducing interactions neosubstrates resulting in their polyubiquitination and proteasomal degradation. glues are clinically precedented have demonstrated ability to degrade proteins‐of‐interest (POIs) previously deemed undruggable due absence traditional small molecule binding pocket. Heterobifunctional proteolysis targeting chimeras (PROTACs) possess ligands for an complex POIs, which chemically linked together, similarly hijack ubiquitin machinery deplete target. There been recent surge number entering clinical trials, particularly directed toward cancer. Nearly all utilize CRL4 CRBN ligase, relatively limited diversity POIs currently targeted. In this review, we provide overview trials perspective on lessons learned from development emerging human data that will be broadly useful those working TPD field.

Language: Английский

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