The Important Role of Endothelium and Extracellular Vesicles in the Cellular Mechanism of Aortic Aneurysm Formation

Homeostasis is a fundamental property of biological systems consisting of the ability to maintain a dynamic balance of the environment of biochemical processes. The action of endogenous and exogenous factors can lead to internal balance disorder, which results in the activation of the immune system and the development of inflammatory response. Inflammation determines the disturbances in the structure of the vessel wall, connected with the change in their diameter. These disorders consist of accumulation in the space between the endothelium and the muscle cells of low-density lipoproteins (LDL), resulting in the formation of fatty streaks narrowing the lumen and restricting the blood flow in the area behind the structure. The effect of inflammation may also be pathological dilatation of the vessel wall associated with the development of aneurysms. Described disease entities strongly correlate with the increased migration of immune cells. Recent scientific research indicates the secretion of specific vesicular structures during migration activated by the inflammation. The review focuses on the link between endothelial dysfunction and the inflammatory response and the impact of these processes on the development of disease entities potentially related to the secretion of extracellular vesicles (EVs).

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THE IMPACT OF PHYSIOLOGICAL AND BIOCHEMICAL PROCESSES IN POTATOES PLANTS ON ACCUMULATION OF STARCH IN TUBERS

Agro-industrial technologies of the Central Russia ◽

10.24888/2541-7835-2019-12-48-56 ◽

2019 ◽

Vol 12 (2) ◽

pp. 48-56

Author(s):

A.V. Butov ◽

◽

A.A. Mandrova ◽

Keyword(s):

Biochemical Processes ◽

The Impact ◽

Physiological And Biochemical

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Human Umbilical Cord Mesenchymal Stem Cell-Derived microRNA-30c-5p-Containing Extracellular Vesicles Alleviates Inflammatory Response of Diabetic Retinopathy Through Modulating the PLCG1/PKC/NF-κB Axis

SSRN Electronic Journal ◽

10.2139/ssrn.3514623 ◽

2020 ◽

Author(s):

Li Huang ◽

Jie Chen ◽

Xiaorong Gao ◽

Yujiao Dan ◽

Jinhua Gan ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Inflammatory Response ◽

Umbilical Cord ◽

Extracellular Vesicles ◽

Human Umbilical Cord

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695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0695 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A737-A737

Author(s):

Loise Francisco-Anderson ◽

Mary Abdou ◽

Michael Goldberg ◽

Erin Troy ◽

...

Keyword(s):

Tumor Microenvironment ◽

Tumor Growth ◽

Extracellular Vesicles ◽

Tumor Immunity ◽

Extracellular Vesicle ◽

The Body ◽

Checkpoint Inhibition ◽

Small Intestinal ◽

The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

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Extracellular Vesicles Analysis in the COVID-19 Era: Insights on Serum Inactivation Protocols towards Downstream Isolation and Analysis

Cells ◽

10.3390/cells10030544 ◽

2021 ◽

Vol 10 (3) ◽

pp. 544

Author(s):

Roberto Frigerio ◽

Angelo Musicò ◽

Marco Brucale ◽

Andrea Ridolfi ◽

Silvia Galbiati ◽

...

Keyword(s):

Extracellular Vesicles ◽

Analytical Techniques ◽

Heat Inactivation ◽

Force Microscopy ◽

Atomic Force ◽

Droplet Pcr ◽

Detergent Treatment ◽

Routine Procedures ◽

The Impact ◽

Mirna Content

Since the outbreak of the COVID-19 crisis, the handling of biological samples from confirmed or suspected SARS-CoV-2-positive individuals demanded the use of inactivation protocols to ensure laboratory operators’ safety. While not standardized, these practices can be roughly divided into two categories, namely heat inactivation and solvent-detergent treatments. These routine procedures should also apply to samples intended for Extracellular Vesicles (EVs) analysis. Assessing the impact of virus-inactivating pre-treatments is therefore of pivotal importance, given the well-known variability introduced by different pre-analytical steps on downstream EVs isolation and analysis. Arguably, shared guidelines on inactivation protocols tailored to best address EVs-specific requirements will be needed among the analytical community, yet deep investigations in this direction have not yet been reported. We here provide insights into SARS-CoV-2 inactivation practices to be adopted prior to serum EVs analysis by comparing solvent/detergent treatment vs. heat inactivation. Our analysis entails the evaluation of EVs recovery and purity along with biochemical, biophysical and biomolecular profiling by means of a set of complementary analytical techniques: Nanoparticle Tracking Analysis, Western Blotting, Atomic Force Microscopy, miRNA content (digital droplet PCR) and tetraspanin assessment by microarrays. Our data suggest an increase in ultracentrifugation (UC) recovery following heat treatment; however, it is accompanied by a marked enrichment in EVs-associated contaminants. On the other hand, solvent/detergent treatment is promising for small EVs (<150 nm range), yet a depletion of larger vesicular entities was detected. This work represents a first step towards the identification of optimal serum inactivation protocols targeted to EVs analysis.

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Effect of Lipopolysaccharides (LPS) and Lipoteichoic acid (LTA) on the Inflammatory Response in Rumen Epithelial Cells (REC) and the Impact of LPS on Claw Explants

Animals ◽

10.3390/ani11072058 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2058

Author(s):

Nicole Reisinger ◽

Dominik Wendner ◽

Nora Schauerhuber ◽

Elisabeth Mayer

Keyword(s):

Epithelial Cells ◽

Inflammatory Response ◽

Structural Integrity ◽

Animal Health ◽

Lipoteichoic Acid ◽

Local Inflammatory Response ◽

Tissue Integrity ◽

Separation Force ◽

The Impact ◽

Rumen Epithelial Cells

Endotoxins play a crucial role in ruminant health due to their deleterious effects on animal health. The study aimed to evaluate whether LPS and LTA can induce an inflammatory response in rumen epithelial cells. For this purpose, epithelial cells isolated from rumen tissue (RECs) were stimulated with LPS and LTA for 1, 2, 4, and 24 h. Thereafter, the expression of selected genes of the LPS and LTA pathway and inflammatory response were evaluated. Furthermore, it was assessed whether LPS affects inflammatory response and structural integrity of claw explants. Therefore, claw explants were incubated with LPS for 4 h to assess the expression of selected genes and for 24 h to evaluate tissue integrity via separation force. LPS strongly affected the expression of genes related to inflammation (NFkB, TNF-α, IL1B, IL6, CXCL8, MMP9) in RECs. LTA induced a delayed and weaker inflammatory response than LPS. In claw explants, LPS affected tissue integrity, as there was a concentration-dependent decrease of separation force. Incubation time had a strong effect on inflammatory genes in claw explants. Our data suggest that endotoxins can induce a local inflammatory response in the rumen epithelium. Furthermore, translocation of LPS might negatively impact claw health.

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Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽

10.1007/s10753-021-01507-x ◽

2021 ◽

Author(s):

Shangrila Parvin ◽

Clintoria R. Williams ◽

Simone A. Jarrett ◽

Sandra M. Garraway

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Response ◽

Inflammatory Cytokine ◽

Cardiovascular Health ◽

Mrna Levels ◽

Post Injury ◽

Cord Injury ◽

And Function ◽

The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

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Temporal Quantitative Proteomics Analysis of Neuroblastoma Cells Treated with Bovine Milk-Derived Extracellular Vesicles Highlights the Anti-Proliferative Properties of Milk-Derived Extracellular Vesicles

Cells ◽

10.3390/cells10040750 ◽

2021 ◽

Vol 10 (4) ◽

pp. 750

Author(s):

Pamali Fonseka ◽

Taeyoung Kang ◽

Sing Chee ◽

Sai V. Chitti ◽

Rahul Sanwlani ◽

...

Keyword(s):

High Risk ◽

Extracellular Vesicles ◽

Quantitative Proteomics ◽

Cell Metabolism ◽

Bovine Milk ◽

Neuroblastoma Cells ◽

Treatment Strategies ◽

Treatment Resistance ◽

Label Free ◽

The Impact

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.

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