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Парадигм Смена в Моноклональном Обнаружении Протеина: От электрофореза до Массовых Спектрометрических методов.

Моноклональный белок (M-протеин) является важнейшим биомаркером для диагностики и мониторинга моноклональных гаммопатий, включая множественную миелому (ММ). Традиционно для обнаружения M-протеинов широко использовались такие основанные на электрофорезе (ЭП) методы, как белковый EP и иммунофиксационный EP. Однако эти методы могут свидетельствовать о низкой чувствительности и недостаточной количественной оценке небольших количеств М-протеина. Для преодоления этих проблем методы, основанные на ЭП, часто сочетаются с количественной оценкой свободных световых цепочек в автоматизированных иммуномасс

Совпадение в аннотации оригинала
Monoclonal protein (M-protein) is a crucial biomarker for diagnosing and monitoring monoclonal gammopathies, including multiple myeloma (MM) … combined with the quantification of serum free light chains in automated immunoassays. Advances in mass spectrometry (MS) have introduced three main approaches for sample preparation: top-down, middle-down, and bottom-up. Middle-down approaches are commonly used with matrix-assisted laser desorption/ionization time-of-flight MS and liquid chromatography-electrospr …

[Rapid determination of venetoclax in plasma by ultra performance liquid chromatography-tandem mass spectrometry].

Leukemia is a malignant tumor of the hematological system characterized by the uncontrolled proliferation of abnormal hematopoietic cells in … ch aims to establish a rapid， sensitive and reliable ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method. This method is used for the quantitative determination of venetoclax in plasma， and its performance was validated. This method employs an electrospray ionization and multiple reaction monitoring （MRM） in the positive ion mode to …

Advances in Mass Spectrometry-Based Proteomics for Kidney Disease Biomarker Discovery and Clinical Translation.

The high prevalence and substantial burden of kidney diseases necessitate advanced approaches to elucidate molecular mechanisms and promote precision medicine. Mass spectrometry (MS)-based proteomics has evolved into a widely used analytical platform, delivering high-sensitivity, high-throughput protein profiling capabilities that have contributed substantially to biomarker discovery, mechanistic dissection, and therapeutic target identification across a broad range of kidney diseases. This review provides a comprehensive overview of MS-based proteomics applications in kidney disease research,…

Immunoprecipitation-mass spectrometry reveals known and novel (NatC, BCS1L) antinuclear antibodies in rheumatoid arthritis.

OBJECTIVE: In a fraction of patients with rheumatoid arthritis (RA), antinuclear antibodies (ANA) are present. However, in most ANA-positive samples from patients with RA, no autoantigens can be identified. We aimed to characterise the ANA landscape in RA and to identify known and novel autoantigens using an unbiased immunoprecipitation-mass spectrometry (IP-MS) approach. METHODS: Sera from 51 ANA-positive, DMARD-naïve patients with RA were analysed by IP-MS using HeLa nuclear or cytoplasmic extracts (depending on the ANA staining pattern). Immunoprecipitated proteins were digested and identi…

Detection of NADH/NAD+ dysregulation in MELAS via diazo-carboxyl click derivatization mass spectrometry.

OBJECTIVES: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder driven by mutations in mitochondrial or nuclear DNA, involving an altered NADH/NAD+-associated redox metabolism as a key pathological mechanism. The traditional metabolomic analyses in MELAS face sensitivity and sample volume limitations, particularly for carboxylic acid metabolites. This study employed a recently established diazo-carboxyl/hydroxylamine-ketone double-click derivatization (DQmB-HA) mass spectrometry method to overcome these barriers, enabling highly sensit…

Identifying lncRNA-Protein Interactions in Hematopoietic Progenitor Cells by Hybridization Capture and Mass Spectrometry.

Long noncoding RNAs (lncRNAs) exert regulatory functions in a wide spectrum of biological contexts, and certain regulatory functions involve … tors of Gas5 lncRNA using HyPR-MS (hybridization purification of RNA-protein complexes, followed by mass spectrometry). A total of 303 proteins were identified as Gas5 lncRNA interactors, five of which were experimentally validated as Gas5 lncRNA interactors by RNA immunoprecipitation qPCR (RIP-qPCR) analysis. The identification of protein interactors with a DDX41- …

Fragmentation Patterns of Chlorogenic Acid Homologs in Positive- and Negative-Ion Mode Mass Spectrometry.

Chlorogenic acids, esters of hydroxycinnamic acids with quinic acid, are abundant plant metabolites with over 400 known derivatives. Due to the limited availability of commercial standards, mass spectrometry fragmentation data are essential for structural identification. We acquired fragmentation spectra of six chlorogenic acid homologs in both positive- and negative-ion modes using direct infusion mass spectrometry. In positive-ion mode, sodiated molecules provided additional structural information in addition to that from protonated molecules, although the difference in substitution position…

Examination of lipid distributions in hydrogel-expanded mouse brain tissue using imaging mass spectrometry.

BACKGROUND: Imaging is essential in biological research, and imaging mass spectrometry uniquely provides a label-free approach with high molecular specificity. However, imaging mass spectrometry is limited in spatial resolution, which in turn limits the biological structures that can be studied. Custom lens setups and altered optical paths can shrink the diameter of the incident laser beam probe in matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to achieve high spatial resolutions (<5 μm). However, these research-grade instruments are complex and expensive, making…

Mass spectrometry-based methods for biofluid biomarkers for progressive diseases: amyloid peptides and dystrophins.

PURPOSE: Using two diseases, Alzheimer's disease and muscular dystrophy as examples, in which many resources have been invested, trends in bioanalytical techniques for detection of peptide or protein biomarkers using mass spectrometry are reviewed using Web of Science database. Amyloid beta peptides have been used to detect Alzheimer's disease, and peptides obtained by tryptic digestion of dystrophin have been used to detect muscular dystrophy. Based on the recent interest in peripheral blood analysis, literature review was focused on biofluid analysis. RESULTS: Both electrospray or matrix-as…

Mass spectrometry footprinting reveals how kinetic stabilizers counteract transthyretin dynamics altered by pathogenic mutations.

The aggregation of transthyretin (TTR) results in life-threatening transthyretin amyloidosis. Familial forms of the disease arise from point … hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) offer critical insights into the conformational dynamics associated with TTR amyloidogenic mutations and the binding of kinetic stabilizers. The results indicate that the design of TTR binders should consider the specific conformational traits …

Bacterial identification using MALDI-TOF mass spectrometry in positive blood cultures: A pilot study.

BACKGROUND: Early pathogen identification in the bloodstream has long been a key focus for microbiologists and clinicians, given its crucial role in patient management. Matrix-assisted laser desorption ionization-time of flight mass spectrometry has emerged as a valuable tool for the direct and rapid identification of organisms from positive blood cultures. OBJECTIVE: This study aimed to evaluate the accuracy, productivity, and feasibility of two methods for the rapid detection of bloodstream infections. METHODS: Two methods were employed in this study: One based on differential centrifugati…

Clickable Multitargeting Cross-Linkers Based on SuFEx for In Vivo Cross-Linking Mass Spectrometry.

Cross-linking mass spectrometry (XL-MS) is a powerful technique to study protein structures and protein-protein interactions. The coverage of amino acids determines the depth of the XL-MS analysis and accuracy of the structural resolution. In this work, we designed and synthesized a pair of novel trifunctional cross-linkers, succinimidyl-propargyl-aryl sulfonyl fluoride (SPSF), for multitargeting cross-linking in vivo. The highly reactive succinimide ester reacts rapidly with Lys residues first; then, the less reactive sulfonyl fluoride reacts with multiple nucleophilic amino acid side chains …

Rapid on-site identification of pyrrolizidine alkaloids in herbal medicines using miniature mass spectrometry.

Pyrrolizidine alkaloids (PAs) are naturally occurring plant toxins with significant multi-organ toxicity, especially hepatotoxicity. Accidental consumption of PAs-containing herbal medicines can lead to severe health consequences, emphasizing the need for rapid and effective detection methods to ensure medicinal safety. In this study, we developed a novel on-site rapid analytical method using paper capillary spray miniature mass spectrometry (PCS-mini MS), and created a database containing 34 different PAs with a detection limit ranging from 0.5 to 2 ng mL-1. This method is particularly suitab…

Structural analysis of synthetic opioids using travelling wave ion mobility-mass spectrometry (TWIM-MS).

Traveling wave ion mobility-mass spectrometry (TWIM-MS) has emerged as a powerful tool for the identification of synthetic opioids, such as fentanyl and its analogs. However, due to its novelty, only a few fentanyl analogs have been studied using this technology and alternative drift gases, apart from the commonly employed nitrogen gas. Here we introduce the largest compendium of measured TWCCSN2, TWCCSHe, and TWCCSCO2 values for fentanyl-related compounds. This compendium of mobility-derived CCS molecular descriptors for precursor [M + H]+ ions can be used to assign fentanyl identities. Here,…

Advances in Chromatography-Free and Ambient Ionization Mass Spectrometry Techniques Toward Clinical Toxicology Testing.

This review presents current scientific literature focused on chromatography-free/ambient ionization mass spectrometry techniques for clinical toxicology. Traditional methods like gas and liquid chromatography, paired with mass spectrometry, are commonly used in clinical laboratories but can be time-consuming, leading to backlogs. To alleviate workloads, immunoassays are often used for screening before confirmatory methods but are susceptible to false positives/negatives especially with structurally similar compounds. Therefore, chromatography-free ionization mass spectrometry methods could ad…

In-Solution Conformation Dynamics of Hemoprotein Catalytic Adaptability Revealed by Ultraviolet Photodissociation Mass Spectrometry.

Despite structure-based mutagenesis being widely used for the rational evolution of engineering enzymes, the in-solution conformation dynamics of enzyme catalytic adaptability is still hard to profile and modulate. Herein, we utilize native mass spectrometry to probe the integrity of hemoprotein overall structure and 193 nm ultraviolet photodissociation to provide residue-level conformation dynamics of catalytic hotspots in peroxidation reaction. We demonstrate that the structure of hemoprotein is generally stable in 25% acetonitrile and methanol aqueous solutions, yet the hotspot conformation…

Non-Invasive Prenatal Screening for Down Syndrome: A Review of Mass-Spectrometry-Based Approaches.

Down Syndrome or Trisomy 21 (T21) is a complex genetic disease characterized by the presence of an extra chromosome 21, which leads to multiple clinical features and manifestations that severely affect the patient's quality of life. Various methods of prenatal screening have been developed over time, allowing informed decision-making. However, a common drawback of the current methods for detecting T21 is their invasive nature. Over the past years, mass-spectrometry-based omics technologies have become a key tool for discovering biomarkers for the prenatal screening of T21, particularly focusin

Fully Automated Deep Learning Enabled Miniature Mass Spectrometry System for Psychoactive Therapeutic Drug Monitoring.

Advancing precision medicine requires efficient small molecule biomarker detection in biofluids, yet existing methods encounter challenges in complexity, portability, and throughput. This study presents an integrated miniature blood processing and mass spectrometry (MS) analysis system, which incorporates automated magnetic solid-phase extraction, self-aspiration sampling miniature mass spectrometer, and deep learning algorithms for automated quantitative analysis. It achieves full automation from sample preparation to detection, demonstrating the capability to analyze serum psychoactive drugs…

Mass Spectrometry Imaging Elucidates the Precise Localization and Site-Specific Functions of Skin Lipids.

Lipids are essential for the skin, playing a crucial role in forming plasma membranes and maintaining the skin's permeability barrier and hy … n of skin lipids, especially intercellular lipids, and investigate their roles and metabolism using mass spectrometry imaging (MSI). We conducted high-resolution (spatial resolution: 5 µm) matrix-assisted laser desorption/ionization (MALDI)-MSI on the lower back and buttocks and created overlay images of skin lipids to clarify their precise localizations. Ceramide …

Categorization and Characterization of Snake Venom Variability through Intact Toxin Analysis by Mass Spectrometry.

The variation in venom between and within snake species has significant implications for snakebite treatment. This highlights the critical importance of studying venom composition and its variations, not only for medical purposes but also from an evolutionary perspective. This study explores analytics for characterizing venom variability, focusing on venom toxin accurate masses, and emphasizes how the complexity of studying snake venom variability can be addressed by using liquid chromatography mass spectrometry (LC-MS) analysis with bioinformatics tools. This was demonstrated by investigating…