actively inhibits the production of extracellular vesicles by human neutrophils.

is the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signaling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation.

Modulation of Heme-Induced Inflammation Using MicroRNA-Loaded Liposomes: Implications for Hemolytic Disorders Such as Malaria and Sickle Cell Disease.

Hemolytic disorders, like malaria and sickle cell disease (SCD), are responsible for significant mortality and morbidity rates globally, specifically in the Americas and Africa. In both malaria and SCD, red blood cell hemolysis leads to the release of a cytotoxic heme that triggers the expression of unique inflammatory profiles, which mediate the tissue damage and pathogenesis of both diseases. MicroRNAs (miRNAs), such as miR-451a and let-7i-5p, contribute to a reduction in the pro-inflammatory responses induced by circulating free hemes.

An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth.

Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV-producing cells has never been demonstrated. Here, as a proof-of-concept, we demonstrate that EV-G12D-mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL-17A/FGF21 axis.

MiR-451a and let-7i-5p loaded extracellular vesicles attenuate heme-induced inflammation in hiPSC-derived endothelial cells.

Hemolysis is associated with many pathologies, including trauma, sepsis, hemorrhagic stroke, malaria, and genetic disorders such as sickle cell disease (SCD). When hemolysis occurs, free-heme drives vascular inflammation, resulting in oxidative tissue damage and cardiometabolic complications. A better understanding of heme clearance and detoxification is essential to preventing sustained tissue damage.

Food for thought: diet-induced impairments to decision-making and amelioration by N-acetylcysteine in male rats.

Rationale: Attempts to lose weight often fail despite knowledge of the health risks associated with obesity and determined efforts. We previously showed that rodents fed an obesogenic diet displayed premature habitual behavioural control and weakened flexible decision-making based on the current value of outcomes produced by their behaviour. Thus, habitual control may contribute to failed attempts to modify eating behaviours.

Separation of U87 glioblastoma cell-derived small and medium extracellular vesicles using elasto-inertial flow focusing (a spiral channel).

Nanoscale and microscale cell-derived extracellular vesicle types and subtypes are of significant interest to researchers in biology and medicine. Extracellular vesicles (EVs) have diagnostic and therapeutic potential in terms of biomarker and nanomedicine applications. To enable such applications, EVs must be isolated from biological fluids or separated from other EV types.

Ginger nanoparticles mediated induction of Foxa2 prevents high-fat diet-induced insulin resistance.

The obesity epidemic has expanded globally, due in large part to the increased consumption of high-fat diets (HFD), and has increased the risk of major chronic diseases, including type 2 diabetes. Diet manipulation is the foundation of prevention and treatment of obesity and diabetes. The molecular mechanisms that mediate the diet-based prevention of insulin resistance, however, remain to be identified.

Experiment, theory, and simulation of a flow-electrical-split flow thin particle separation device.

Herein, we describe the simulation of a novel flow-electrical-split flow thin (Fl-El-SPLITT) separation device and validate it using existing theory and experimentation for the first time using polystyrene particles of 28 and 1000 nm diameters. The fraction of particles exiting selected ports with DC El-SPLITT is predicted with existing theory, but the theory does not include AC fields, nor does it incorporate the use of crossflows. Using DC fields the El-SPLITT simulation and theory calculated transition points result in the same values.

Development and Testing of a Continuous Flow-Electrical-Split-Flow Lateral Transport Thin Separation System (Fl-El-SPLITT).

In this work, a new high-volume, continuous particle separation device that separates based upon size and charge is described. Two continuous flow-electrical-split-flow lateral transport thin (Fl-El-SPLITT) device architectures (a platinum electrode on a porous membrane and a porous graphite electrode under a membrane) were developed and shown to improve particle separations over a purely electrical-SPLITT device. The graphite FL-El-SPLITT device architecture achieved the best separation of approximately 60% of small (28 nm) vs large (1000 nm) polystyrene particles.

Hemoglobin Genotypes Modulate Inflammatory Response to Infection.

In 2018, 228 million cases and 405,000 malaria-associated deaths were reported worldwide with a majority being in Africa. A wide range of factors, including parasitemia, host immunity, inflammatory responses to infection, and host hemoglobin genotype, mediate the severity of malaria. Among the hemoglobinopathies, hemoglobin S (HbS) is caused by a single amino acid substitution of Glutamic Acid replaced by Valine at the sixth position of the beta-globin chain (E6V).

Characterization of Human Glioblastoma versus Normal Plasma-Derived Extracellular Vesicles Preisolated by Differential Centrifugation Using Cyclical Electrical Field-Flow Fractionation.

Although many properties for small extracellular vesicles (sEVs, formerly termed "exosomes") isolated at ∼100 000 are known, a wide range of values are reported for their electrophoretic mobility (EM) measurements. This paper reports for the first time the effect of dilution on the EM of U87 glioblastoma cell-derived and plasma-derived sEVs and medium size EVs (mEVs, commonly termed "oncosomes") preisolated by differential centrifugation. Furthermore, the effect of resalting on the EM of sEVs and mEVs was evaluated.

Natural melanoma-derived extracellular vesicles.

Melanoma cells produce a variety of extracellular vesicle (EV) types including shedding vesicles and exosomes (EXOs). These EVs are defined by their mechanism of cellular production. To date, the majority of EV investigations has centered around melanoma EXOs or small EVs (sEVs).

Detection of Inflammation-Related Melanoma Small Extracellular Vesicle (sEV) mRNA Content Using Primary Melanocyte sEVs as a Reference.

Melanoma-derived small extracellular vesicles (sEVs) participate in tumor pathogenesis. Tumor pathogenesis is highly dependent on inflammatory processes. Given the potential for melanoma sEVs to carry tumor biomarkers, we explored the hypothesis that they may contain inflammation-related mRNA content.

Exosome Isolation: Cyclical Electrical Field Flow Fractionation in Low-Ionic-Strength Fluids.

The influence of buffer substitution and dilution effects on exosome size and electrophoretic mobility were shown for the first time. Cyclical electrical field flow fractionation (Cy-El-FFF) in various substituted fluids was applied to exosomes and other particles. Tested carrier fluids of deionized (DI) water, 1× phosphate buffered saline (PBS), 0.

Melanoma exosomes promote mixed M1 and M2 macrophage polarization.

Macrophages are key participants in melanoma growth and survival. In general, macrophages can be classified as M1 or M2 activation phenotypes. Increasing evidence demonstrates that melanoma exosomes also facilitate tumor survival and metastasis.

The association of exosomes with lymph nodes.

Cells produce extracellular nanovesicles known as exosomes that transport information between tissue microenvironments. Exosomes can engage and regulate the function of various immune cell types facilitating both normal and pathological processes. It follows that exosomes should also associate with lymph nodes containing immune cells.

Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes.

Angiogenesis is a key process in the preparation of lymph nodes for melanoma metastasis. Granulocyte macrophage colony stimulating factor (GM-CSF) induces hypoxia inducible factor 1 alpha (HIF-1α) in M1 or HIF-2α in M2 polarized macrophages. HIF-1α promotes neoangiogenesis while HIF-2α facilitates morphogenic normalization of neovasculature.

Post isolation modification of exosomes for nanomedicine applications.

Exosomes are extracellular nanovesicles. They innately possess ideal structural and biocompatible nanocarrier properties. Exosome components can be engineered at the cellular level.

Melanoma exosomes enable tumor tolerance in lymph nodes.

Melanoma preferentially spreads via lymph nodes. Melanoma exosomes can induce angiogenesis and immune suppression. However, a role for melanoma exosomes in facilitating tumor tolerance in lymph nodes has not been considered.

A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM.

Exosomes participate in cancer metastasis, but studying them presents unique challenges as a result of their small size and purification difficulties. Asymmetrical field flow fractionation with in-line ultraviolet absorbance, dynamic light scattering, and multi-angle light scattering was applied to the size separation and characterization of non-labeled B16-F10 exosomes from an aggressive mouse melanoma cell culture line. Fractions were collected and further analyzed using batch mode dynamic light scattering, transmission electron microscopy and compared with known size standards.

Magnetic resonance imaging of melanoma exosomes in lymph nodes.

Purpose: Exosomes are cell derived extracellular nanovesicles that relay molecular signals pertinent to both normal physiologic and disease processes. The ability to modify and track exosomes in vivo is essential to understanding exosome pathogenesis, and for utilizing exosomes as effective diagnostic and therapeutic nanocarriers to treat diseases.

Methods: We recently reported a new electroporation method that allow exosomes to be loaded with superparamagnetic iron oxide nanoparticles for magnetic resonance tracking.

Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity.

Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro.

Maximizing exosome colloidal stability following electroporation.

Development of exosome-based semisynthetic nanovesicles for diagnostic and therapeutic purposes requires novel approaches to load exosomes with cargo. Electroporation has previously been used to load exosomes with RNA. However, investigations into exosome colloidal stability following electroporation have not been considered.