PROTEOMICS – Clinical Applications最新文献

Bronchoalveolar lavage fluid (BALF) has long been used for diagnosing various lung diseases through its cellular components. However, the clinical utility of biomolecules in the BALF remains largely unexplored. Recently, mass spectrometry-based proteomics has been applied to profile the BALF proteomes to identify novel biomarkers for lung diseases. This review discusses the current progress in the field of BALF proteomics and highlights its potential as a valuable source of biomarkers for different lung diseases. Additionally, we explored the latest advancements and findings from BALF studies. Finally, we address the current limitations and propose future directions and research opportunities to advance the study of BALF.

Purpose: Proteins are key effectors of biological functions and play roles in signaling, transport, growth, repair, and immunity. Vitamin D biomarkers may be reflected in the plasma proteome. The aim of this discovery study was to identify novel proteins associated with vitamin D supplementation.

Experimental design: We examined cross-sectional associations between vitamin D supplementation and plasma proteins in the Atherosclerosis Risk in Communities (ARIC) study at visit 5 (2011-2013). An untargeted proteomic platform (SomaScan version 4, SomaLogic) was used to quantify relative abundance for 4955 proteins. We compared protein levels in vitamin D supplement users and nonusers using covariate-adjusted multivariable linear regression models.

Results: Of 5011 participants analyzed (mean age 76 [SD 5] years), 2255 (45%) used vitamin D supplements. Fifty-one proteins were associated with vitamin D supplementation at a false discovery rate-adjusted p < 0.05. Most proteins (33 of 51) were lower in users than nonusers. After adjusting for other supplement use (multivitamin/mineral, omega-3, B vitamins, and vitamin C), 7 proteins remained significantly associated with vitamin D supplementation.

Conclusions and clinical relevance: Chondroadherin, parathyroid hormone, transcobalamin-1, osteomodulin, collagen type II, and bone sialoprotein 2 were lower, while sclerostin was higher, in vitamin D users than nonusers. These proteins are potential markers of vitamin D in older adults and highlight vitamin D-related metabolic pathways.

Purpose: During COVID-19, significant changes in protein abundance can be linked with disease-related processes. The mass spectrometry-based proteomics of COVID-19-related biomarkers can help with the prognosis and diagnosis of this severe disease.

Design: Here, we surveyed scientific works in terms of proteomic analysis of solid tissues and non-blood fluids from COVID-19 patients. Works published since 2022 to date have been covered.

Results: Brain, lymph nodes, heart, spleen, aorta walls, liver, adrenal gland and kidneys were investigated as solid organs/tissues. The non-blood fluids involved exhaled breath particles, airway mucus, saliva, swabs, colostrum/milk and urine. The provided table depicts studies/experimental platforms to analyse COVID-19-related candidate protein biomarkers.

Conclusion: Even eminent research input has been made in this field, continuation towards deeper findings should be made. Translation of proteomics into the clinics to help with diagnostics and therapeutical strategies, is a highly important task. The analysed candidate protein biomarkers are the perspective molecules for pending clinical decisions making and treatments.

Purpose: Embryo-maternal signaling during the establishment of pregnancy in horses remains one of the biggest mysteries in large animal physiology. Early pregnancy loss represents a major source of economic loss to the breeding industry. This study aimed to investigate the systemic changes associated with early pregnancy by mapping the proteome of blood plasma at 14 days in pregnant and non-pregnant mares.

Experimental design: Plasma proteomes were analysed in commercially bred pregnant (n = 17) and non-pregnant (n = 17) Thoroughbred mares at 14 days after ovulation, using high-resolution mass spectrometry. Day 14 histotroph and yolk sac fluid were also profiled and datasets were integrated through pathway analysis.

Results: We identified 229 total protein IDs, with 12 increased and 10 decreased significantly in pregnant versus non-pregnant plasma. To gain functional insight, these data were aligned with proteomes of 14-day pregnant mare uterine fluid (n = 4; 1358 IDs) and conceptus fluid (soluble proteins within the yolk sac fluid; n = 4; 1152 IDs), and further interrogated using gene ontology databases and pathway analysis.

Conclusions and clinical relevance: These analyses identified consistent systemic changes in the mare's proteome that indicate a profound and specific immune response to early pregnancy, which appears to precede the systemic endocrine response to pregnancy. Integrated pathway analysis suggests that embryo-maternal interactions in early pregnancy may mimic elements of the virus-host interaction to modulate the maternal immune response. Transthyretin (TTR) and uteroglobin (SCGB1A1) were respectively down- and upregulated in plasma while also present in uterine fluid, and are proposed to be key proteins in early pregnancy establishment. These findings contribute significantly to our knowledge of early pregnancy in the mare and identify potential new avenues for developing clinical approaches to reduce early embryo loss.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy which mainly consists of serous, mucinous, clear cell, and endometrioid subtypes. Due to the lack of classic symptoms at an early stage, EOC usually presented as advanced tumors with local and/or distant metastasis. Although a large portion of EOC was initially platinum-sensitive, most patients would acquire resistance to common chemotherapeutic agents. These aforementioned issues lead to a challenge for clinical treatments and unsatisfying outcomes. Previous studies have demonstrated the genetic features of EOC are hard to target and the alterations at DNA and RNA levels are not fully represented at the protein expression profiles which made it more complex. In recent years, a panel of studies attempted to explore the key proteins involved in the development and progression of EOC using high-throughput proteomic technologies. We herein summarized them to provide a full view of this topic.

Purpose: Multiple Sclerosis is an inflammatory neurodegenerative disease characterised by blood-brain barrier dysfunction and leukocyte infiltration into the CNS. Platelets are best known for their contributions to haemostasis, however, upon activation, platelets release an abundance of soluble and vesicular-associated proteins, termed the platelet releasate (PR). This milieu contains numerous inflammatory and vasoactive proteins, that can attract leukocytes and alter endothelial permeability.

Experimental design: We aimed to characterise the PR of Relapsing-Remitting multiple sclerosis (RRMS) patients, previously characterized regarding thrombin generation dynamics compared to healthy controls. We carried out LFQ proteomic profiling of the PR from 15 RRMS and 19 aged-matched healthy controls.

Results: We identified 9 proteins increased and 16 proteins decreased in the PR of RRMS patients. Platelet/endothelial cell-adhesion molecule-1 (PECAM-1) was uniquely found in healthy control PR and circulating levels of PECAM-1 were significantly lower in RRMS patient samples. GO analysis revealed a strong link between altered proteins and extracellular vesicles (EVs). Small EV levels were significantly reduced in RRMS PR compared to healthy PR and showed a negative correlation with PECAM-1 levels in RRMS plasma.

Conclusions and clinical relevance: Our findings suggest that platelet reactivity may be linked to disease activity, even in periods of disease remission.

Purpose: The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in the role of the hippocampus remain largely unexplored.

Experimental design: An LC-MS/MS bottom-up proteomics analysis of three human hippocampal tissue samples was applied to profile the lactylation map in human hippocampi under normal physiological conditions.

Results: We identified 2579 quantifiable Class I lactylated sites in 853 proteins, of which contained four types of modification motifs. Cellular localization analysis implies that a majority of lactylated proteins were distributed in the cytoplasm. Functional enrichment analysis showed that lactylated proteins were mainly involved in energy metabolic pathways. In addition, we found that the lactylation on histones exhibits a certain degree of conservation across different tissues. Compared with previously reported lactylation databases, 213 lactylated proteins were identified for the first time in this study.

Conclusion and clinical relevance: The first global lactylated proteins atlas of human hippocampi was reported in this study. Our work provides a reliable foundation for further research on lactylation in the hippocampus under physiological conditions.

Saliva is a child appropriate biofluid, but it has not previously been used to evaluate the systemic response to burn injury in children. The aim of this study was to investigate the salivary proteome of children with small area thermal skin burns relative to different burn characteristics (mechanism, time to re-epithelialization and risk of emotional distress). SWATH Mass Spectrometry was used to quantify the abundance of 742 proteins in the saliva of children with burns (n = 22) and healthy controls (n = 37). Eight proteins were differentially abundant in the saliva of children with burns compared to healthy children, and these were associated with immune processes, epidermal cell differentiation and transferrin receptor binding. Eleven proteins were differentially abundant in patients with burns of different mechanisms. Scald burns had an over-representation of immune/inflammatory response processes, and contact burns had an over-representation of cornification, intermediate filament assembly and cell death cellular processes. Four proteins were elevated in patients who were at high risk for emotional distress and 15 proteins were correlated with time to wound re-epithelialization. This pilot study proves that saliva can be used for paediatric biomarker discovery and can be used as a diagnostic and prognostic sample to investigate systemic changes in a paediatric burn cohort.

Background: IL4 is a versatile cytokine essentially known for differentiation, proliferation and cell death in cells. Its dysregulation has been found to be associated with the development of inflammatory disorders.

Objective: The goal of the current investigation is to identify and select non-synonymous single-nucleotide polymorphisms (nsSNPs) in the IL-4 gene by employing computational methods which may have a potential functional impact on the occurrence of disease.

Method and result: Six different nsSNPs were predicted to be deleterious based on the consensus of different algorithms: SIFT, Polyphen2 (Humdiv and HumVar), PredictSNP and SNP&GO. I-mutant and MuPro assessment revealed a decrease in the stability of these mutants except K150M. Modelling was then carried out to build the wild type along with its mutants, followed by superimposition of the wild type with mutants to evaluate the RMSD value, which lies between 0.26 and 0.34. Simulation results of mutant models, along with wild type, showed that four of the mutants (N113Y, A118G, R109W and K150M) deviated most and were unstable. A118G showed a significant deviation from the wild type, while V53A and C123R were stable.

Conclusion: The finding establishes the evidence that the identified six nsSNPs of IL-4 can be the new entrant presenting their candidature for genetic testing.

Purpose: Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial hemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes.

Experimental design: Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation, and neuronal signaling. Here, we investigated activity-based protein profiling (ABPP) coupled to liquid chromatography-mass spectrometry (LC-MS) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS).

Results: Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism.

Conclusions and clinical relevance: To our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.