Proteome in platelet of sepsis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Meiling Su
PROVIDER: PXD053408 | iProX | Wed Jun 26 00:00:00 BST 2024
REPOSITORIES: iProX
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Project description:Platelets and megakaryocytes are critical players in immune responses. Recent reports suggest infection and inflammation alter the megakaryocyte and platelet transcriptome to induce altered platelet reactivity. We examined if non-viral sepsis induces differential platelet gene expression and reactivity. Non-viral sepsis significantly upregulated IFITM3, an interferon responsive gene that restricts viral replication
2022-12-01 | GSE210797 | GEO
Project description:Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis
| PRJEB45262 | ENA
Project description:Pediatric sepsis is a leading cause of mortality in children across the world. Within pediatric sepsis, how developmental age-specific host immune response impact on the occurrence and development of pediatric sepsis is still unknown, especially between infants and toddlers, which were the major susceptible age groups in sepsis. Experimental design In this study, we applied a nested case-control study strategy and analyzed the plasma proteomes of pediatric sepsis patients between infants and toddlers in comparison to their age-matched controls respectively. Each age group consists of three subgroups with different outcomes. One hundred and ten plasma samples were pooled into 16 samples for quantitative identification by LC-MS/MS. Results It was totally quantified 677 proteins. In comparison to toddlers, infant sepsis patients were characteristic with dominant neutrophil-mediated defense, suppressed adaptive immunity and NK-mediated cytotoxicity. Besides, pentose phosphate pathway was more up-regulated in infants and associated with poor outcome. Moreover, combined Hp and Thbs1 with the AUC value of 0.958 (95%CI, 0.868, 1.000) was confirmed as potential infant-adapted prognostic marker of poor outcome in sepsis. Conclusion and clinical relevance Our proteomic analysis of age-associated pediatric sepsis combined with clinical laboratory data provided a comprehensive insight into the complex, multifactorial heterogeneous host response to pediatric sepsis and allowed identification of critical differences between infant and toddler sepsis. Moreover, we confirmed that combined Hp and Thbs1 is more infant-adapted and serves as a potential prognostic biomarker for poor outcome of infant sepsis, promoting the application of age-adapted precision medicine in pediatric sepsis.
2021-11-01 | PXD026656 | Pride
Project description:Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen is a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen where interleukin-3 (IL-3) induced their differentiation into megakaryocytes. In the spleen, immune-skewed megakaryocytes produced a CD40L-high platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.
2022-02-14 | GSE196607 | GEO
Project description:Sepsis represents a complex disease with dysregulated inflammatory response and high mortality rate. Long noncoding RNAs (lncRNAs) have been reported to play regulatory roles in a variety of biological processes. However, studies evaluating the function of lncRNAs in pediatric sepsis are scarce, and current knowledge of the role of lncRNAs in pediatric sepsis is still limited. We explored the expression patterns of both lncRNAs and mRNAs between pediatric sepsis patients and healthy controls based on a comprehensive microarray analysis.
2020-02-14 | GSE145227 | GEO
Project description:The temporal evolution of sepsis was monitored by transcriptional profiling of five critically ill children with meningococcal sepsis and sepsis-induced multiple organ failure. Blood was sampled at 6 time points during the first 48 hours of their admission to pediatric intensive care, where the children received standard clinical treatment including organ support and antimicrobial therapy. Striking transcript instability was observed over the 48 hours, with increasing numbers of regulated genes over time. Most notably, proposed biomarkers for sepsis risk stratification also showed expression instability, with varied expression levels over 48 hours. This study demonstrates the extent of the complexity of temporal changes in gene expression that occur during the evolution of sepsis-induced multiple organ failure. Importantly, stratification tools that propose expression of biomarkers must take into account the temporal changes, over the use of single snapshots that may be less informative.
2013-04-03 | E-MEXP-3850 | biostudies-arrayexpress
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.
2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress
Project description:<p>Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.</p><p><br></p><p>In MTBLS1382, to validate lipid mediator species identified with the Qtrap instrument (<a href='https://www.ebi.ac.uk/metabolights/MTBLS1381' rel='noopener noreferrer' target='_blank'>https://www.ebi.ac.uk/metabolights/MTBLS1381</a>), the Thermo QEx HF was used to perform high resolution MS full scan (HR-FS) and data independent acquisition (DIA) analyses between 200-400 m/z with a 20 m/z step size. DIA method preparation and data analysis were performed with Skyline. We used LipidCreator as an external tool in Skyline to generate a collision-energy specific transition list for the mediators 12-HETE, 13-HODE, 15-HETE, arachidonic acid (AA),<strong> </strong>docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and thromboxane B2 (TXB2) and their deuterated counterparts 12-HETE-d8, 13-HODE-d4, 15-HETE-d8, AA-d8, DHA-d5, EPA-d5 and TXB2-d4, at a normalized collision energy NCE=21. We also used LipidCreator's relative fragment intensity prediction model to generate a custom spectral library for the light and heavy mediators. We transfered both the transition list and the spectral library directly from LipidCreator to Skyline and exported the dot product values after manual fragment peaks review.</p><p><br></p><p>Studies linked to this manuscript include;</p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1333' rel='noopener noreferrer' target='_blank'>MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HF</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1334' rel='noopener noreferrer' target='_blank'>MTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTof</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1369' rel='noopener noreferrer' target='_blank'>MTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1375' rel='noopener noreferrer' target='_blank'>MTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standard</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1376' rel='noopener noreferrer' target='_blank'>MTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identification</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1381' rel='noopener noreferrer' target='_blank'>MTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1382' rel='noopener noreferrer' target='_blank'>MTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation</a></p>
2020-04-15 | MTBLS1382 | MetaboLights
Project description:Immune thrombocytopenia (ITP) is a common platelet disorder in pediatric patients. Pediatric and adult ITP have been associated with sialic acid alterations, but the pathophysiology of ITP remains elusive, and ITP is often a diagnosis of exclusion. Our analysis of pediatric ITP plasma samples showed increased anti-Thomsen-Friedenreich antigen (TF-antigen) antibody representation, suggesting increased exposure of the typically sialylated and cryptic TF-antigen in these patients. The O-glycan sialyltransferase St3gal1 add sialic acid specifically on the TF-antigen. To understand if TF-antigen exposure associates with thrombocytopenia, we generated a mouse model with targeted deletion of St3gal1 in megakaryocytes (MK) (St3gal1MK-/-). TF-antigen exposure was restricted to MKs and resulted in thrombocytopenia. Deletion of Jak3 in St3gal1MK-/- mice normalized platelet counts implicating involvement of immune cells. Interferon-producing Siglec H-positive bone marrow (BM) immune cells engaged with O-glycan sialic acid moieties to regulate type I interferon (IFN-I) secretion and platelet release (thrombopoiesis), as evidenced by partially normalized platelet count following and inhibition of interferon and Siglec H receptors. Single cell RNAseq determined that TF-antigen exposure by MKs primed St3gal1MK-/- BM immune cells to release IFN-I. Single cell RNAseq further revealed a new population of immune cells with a plasmacytoid dendritic cell (pDC)-like signature and concomitant upregulation of immunoglobulin re-arrangement gene transcripts Igkc and Ighm, suggesting additional immune regulatory mechanisms. Thus, aberrant TF-antigen moieties, often found in pathological conditions, regulate immune cells and thrombopoiesis in the BM, leading to reduced platelet count.
2021-06-29 | GSE179067 | GEO
Project description:Background: The role of viral infections as a mediator of systemic immune dysfunction leading to sepsis has received limited attention compared to the bacterial pathogens. The COVID-19 pandemic and the increased cases of sepsis in the absence of known bacterial pathogens have highlighted the clinical relevance of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolic characteristics to shed light on the molecular mechanisms underlying the pathological conditions of viral sepsis in COVID-19. Methods: We retrospectively analyzed data from 231 hospitalized patients with confirmed COVID-19 admitted to three hospitals in China. The presence of viral sepsis was diagnosed with SOFA score 2 in the absence of bacterial infection. Demographics, clinical, and laboratory parameters, as well as clinical outcomes, were obtained from electronic chart reviews. Plasma samples were obtained from a subset of these patients (23 patients in the Viral Non-Sepsis [VNS] group and 14 patients in the Viral Sepsis [VS] group) to analyze proteomic and metabolic profiles. Findings: The viral sepsis group exhibited severe disease, as indicated by elevated markers of both pulmonary (ARDS) and systemic disease (liver, kidney, and cardiac injury). Consistent with known immune paralysis observed in sepsis, subjects with viral sepsis were more susceptible to secondary infections by bacterial and fungal pathogens. Overall, viral sepsis led to an increased length of ICU stay, required invasive mechanical ventilation and a significant increase in mortality compared to the non-viral sepsis group. At the molecular levels, we identified unique metabolic and proteomic signatures that suggest a substantial contribution of the coagulation and platelet dysfunction pathways to systemic pathologies. Interpretation: Viral sepsis presents an underrecognized threat contributing to high mortality. Specific metabolic and proteomic changes demonstrated coagulation and platelet dysfunction as key pathological pathway in viral sepsis.
2024-03-03 | PXD050303 |