Adipose derived stem cell extracellular vesicles modulate primary human macrophages to an anti-inflammatory phenotype in vitro.

EVs released by adipose derived stem cells (ADSCs) have shown promise as a therapeutic for tissue repair because of their purported immune-regulatory properties. Extracellular vesicles (EVs) from ADSCs could be beneficial in improving graft retention rates for autologous fat grafting (AFG) post-mastectomy as, currently, grafted tissue rates are variable. Enriching grafted tissue with ADSC-EVs may improve retention rates by modulating macrophages resident within both the breast and lipoaspirate.

CPHEN-017: Comprehensive phenotyping of neutrophil extracellular traps (NETs) on peripheral human neutrophils.

With the recent discovery of their ability to produce neutrophil extracellular traps (NETs), neutrophils are increasingly appreciated as active participants in infection and inflammation. NETs are characterized as large, web-like networks of DNA and proteins extruded from neutrophils, and there is considerable interest in how these structures drive disease in humans. Advancing research in this field is contingent on developing novel tools for quantifying NETosis.

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC.

Neutrophil-Enriched Biomarkers and Long-Term Prognosis in Acute Coronary Syndrome: a Systematic Review and Meta-analysis.

Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute coronary syndrome (ACS) patients. We conducted a systematic review to examine neutrophil-enriched biomarkers and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS. We identified twenty-seven studies including 17,831 patients with ACS.

Ensuring Full Spectrum Flow Cytometry Data Quality for High-Dimensional Data Analysis.

Full spectrum flow cytometry (FSFC) allows for the analysis of more than 40 parameters at the single-cell level. Compared to the practice of manual gating, high-dimensional data analysis can be used to fully explore single-cell datasets and reduce analysis time. As panel size and complexity increases so too does the detail and time required to prepare and validate the quality of the resulting data for use in downstream high-dimensional data analyses.

Importance of the endometrial immune environment in endometrial cancer and associated therapies.

Endometrial cancer is rising in prevalence. The standard treatment modality of hysterectomy is becoming increasingly inadequate due primarily to the direct link between endometrial cancer and high BMI which increases surgical risks. This is an immunogenic cancer, with unique molecular subtypes associated with differential immune infiltration.

Increased levels of low density neutrophils (LDNs) in myocardial infarction.

Background: Recent evidence suggests that neutrophils are highly plastic cells that can display heterogeneous phenotypes. Low-density neutrophils (LDNs) have been described in many inflammatory conditions, and are thought to represent an immature, hyperactivated subtype of neutrophils. Neutrophils are significantly involved in the inflammatory response to myocardial infarction (MI), although we do not know the extent to which LDNs exist, or function, in MI.

A combined biomarker approach for characterising extracellular matrix profiles in acute myocardial infarction.

Extracellular matrix (ECM) biomarkers are useful for measuring underlying molecular activity associated with cardiac repair following acute myocardial infarction (AMI). The aim of this study was to conduct exploratory factor analysis (EFA) to examine the interrelationships between ECM biomarkers, and cluster analysis to identify if distinct ECM profiles could distinguish patient risk in AMI. Ten ECM biomarkers were measured from plasma in 140 AMI patients: MMP-2, -3, -8, -9, periostin, procollagen I N-Terminal propeptide, osteopontin, TGF-β1, TIMP-1 and -4.

Linking Neutrophil Extracellular Traps and Platelet Activation: A Composite Biomarker Score for Predicting Outcomes after Acute Myocardial Infarction.

Background:  Activation of both platelets and neutrophils can contribute to the risk of major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). Neutrophil extracellular traps (NETs) are an important product of the platelet-neutrophil axis and exaggerate vascular damage in cardiovascular disease. Additionally, activated platelets can drive NETosis and are directly linked to thromboembolic risk.

Effects and Side Effects of Platelet Transfusion.

Aside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage.

An IL-6-IL-8 score derived from principal component analysis is predictive of adverse outcome in acute myocardial infarction.

Introduction: Many studies have shown that elevated biomarkers of inflammation following acute myocardial infarction (AMI) are associated with major adverse cardiovascular events (MACE). However, the optimal way of measuring the complex inflammatory response following AMI has not been determined. In this study we explore the use of principal component analysis (PCA) utilising multiple inflammatory cytokines to generate a combined cytokine score that may be predictive of MACE post-AMI.

Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis.

While platelet function has traditionally been described in the context of maintaining vascular integrity, recent evidence suggests that platelets can modulate inflammation in a much more sophisticated and nuanced manner than previously thought. Some aspects of this expanded repertoire of platelet function are mediated via expression of Toll-like receptors (TLRs). TLRs are a family of pattern recognition receptors that recognize pathogen-associated and damage-associated molecular patterns.

Platelets modulate multiple markers of neutrophil function in response to in vitro Toll-like receptor stimulation.

Introduction: In addition to their role in facilitating leukocyte-mediated inflammation, platelets can dampen leukocyte pro-inflammatory responses in some contexts. Consequently, platelets are increasingly appreciated as regulators of inflammation. Together, platelets and neutrophils play a role in inflammation through Toll-like receptor (TLR) expression, although we do not fully understand how platelets shape neutrophil responses to TLR stimulation.

Immunoglobulin G levels predicts risk of recurrent adverse cardiovascular events in myocardial infarction patients.

Patients with myocardial infarction (MI) are at an increased risk of experiencing recurrent major adverse cardiovascular events (MACE) but predicting MACE has remained challenging. Immunoglobulins are implicated in cardiovascular disease, although the predictive value of total immunoglobulin G (IgG) has not yet been evaluated in a secondary prevention setting. This study examined whether total IgG is predictive of MACE in an MI population, and how total IgG compared to the predictive value of C-reactive protein (CRP), an acute inflammatory marker.

Platelets regulate leucocyte responses to Toll-like receptor stimulation.

Objectives: Platelets are important regulators of vascular thrombosis and inflammation and are known to express Toll-like receptors (TLRs). Through TLRs, platelets mediate a number of responses by interacting with leucocytes. Here, we report the extent to which platelets modulate peripheral blood mononuclear cells (PBMCs) and granulocyte responses to TLR4, TLR2/1 and TLR2/6 stimulation in healthy subjects.

The effects of aspirin and ticagrelor on Toll-like receptor (TLR)-mediated platelet activation: results of a randomized, cross-over trial.

Platelet activation underlies the pathology of an acute myocardial infarction (AMI), and dual antiplatelet therapy (DAPT) is administered post-AMI to limit this activation. Platelets express Toll-like receptors (TLRs) 1, 2, and 4 and become potently activated in response to TLR2/1 and TLR4 stimulation. However, it is unknown whether antiplatelet agents can protect against platelet activation via these TLR pathways.

Platelet Toll-like receptor (TLR) expression and TLR-mediated platelet activation in acute myocardial infarction.

Both platelets and Toll-like receptors (TLRs) contribute to acute myocardial infarction (AMI). Platelet activation can occur post-AMI and despite treatment with anti-platelet therapy. TLRs may represent an alternative platelet activation pathway, although the role of platelet-TLRs in AMI is poorly characterized.

Toll-like receptor 9 expression and activation in acute coronary syndrome patients on dual anti-platelet therapy.

Introduction: The Toll-like receptor 9 (TLR9) pathway can activate platelets but its role in acute coronary syndromes (ACS) is unknown. This study examined TLR9 expression and platelet activation in response to ODN2006, a TLR9 agonist, in healthy subjects and in ACS subjects treated with dual anti-platelet therapy (DAPT).

Materials And Methods: TLR9 expression was examined in both resting and thrombin receptor activator peptide (TRAP)-activated platelets (1 and 10μM) from healthy and ACS subjects by flow cytometry.