Biology subjects

de Necochea Campion, R.

Publications and source records attributed to de Necochea Campion, R..

3 recordsLinked to original sources

bioRxiv2025

Increased mannosylation of extracellular vesicles in Long COVID plasma provides a potential therapeutic target for Galanthus nivalis agglutinin (GNA) affinity resin

There is no proven therapy for Long COVID, a post-acute illness characterized by a myriad of diverse symptoms including fatigue, dyspnea, and brain fog following SARS-CoV-2 infection. Extracellular vesicles (EVs) have been implicated in Long COVID pathogenesis by promoting viral and inflammatory signaling with their molecular cargo. In this study, we investigated whether EV abundance and glycome characteristics are altered in plasma from people with Long COVID and whether they can be targeted for removal using a glycan-binding affinity resin. Large (100-500 nm) and small (40-200 nm) EVs were isolated from plasma of participants in the post-acute phase of COVID-19 and analyzed by nanoparticle flow cytometry to measure concentration and glycan characteristics. Plasma of those with Long COVID contained elevated levels of both large and small EVs, and mannose-positive large EVs were significantly increased in comparison to recovered controls (p < 0.05). EV capture assays using Galanthus nivalis agglutinin (GNA) affinity resin demonstrated small EV removal positively correlated with mannose-positive EV abundance (r = 0.341, p < 0.05). NanoString analyses identified seven EV-associated miRNAs significantly depleted by GNA affinity resin treatment of plasma. PROGENy pathway inference of validated miRNA-mRNA interactions suggests these reductions may lead to a downregulation of JAK-STAT signaling and upregulation of Estrogen, VEGF, and PI3K pathways, resulting in a favorable rebalancing of immune and tissue-repair networks. These findings reveal specific glycome EV-miRNA cargo signatures in Long COVID and the potential clinical benefits of a lectin capture therapeutic strategy to remove these pathogenic vesicles and their inflammatory cargo.

molecular biology↗

bioRxiv2025

Ex Vivo Removal of CD41 positive platelet microparticles from Plasma by a Medical Device containing a Galanthus nivalis agglutinin (GNA) affinity resin

BackgroundPlatelet microparticles (PMP) are elevated in and associated with disease activity in a number of diseases including cancer, neurological conditions, autoimmune diseases, and infectious diseases. This finding raises the possibility of a removal of these microparticles as a therapeutic strategy. The Hemopurifier is an experimental device consisting of a plasma separator and an affinity resin containing Galanthus nivalis agglutinin (GNA) affinity resin that has previously been shown to remove extracellular vesicles in vitro and in vivo. In this proof on concept study, we sought to determine ex vivo removal of platelet-derived microparticles from healthy human plasma by the Hemopurifier. MethodsTwo hundred milliliters of thawed healthy human plasma were circulated over the Hemopurifier device at a rate of 100 mL/minute. Plasma samples were taken at time points equivalent to a 4-, 6- and 8-hour clinical Hemopurifier session in a healthy adult. Microparticles were isolated from these timepoints and analyzed for treatment concentration changes. Platelet microparticle counts were determined by binding to antiCD41. ResultsThe Hemopurifier removed 98.5% of platelet microparticles during the equivalent of a 4-hour clinical session. ConclusionsWe demonstrated that an extracorporeal device with a GNA affinity resin removes platelet microparticles from normal healthy plasma. Next steps would be demonstration of the removal of PMPs from plasma by the Hemopurifier in different disease states and characterization of the cargo within removed PMPs.

immunology↗

bioRxiv2024

The Hemopurifier removes extracellular vesicles and microRNAs from renal perfusates following controlled oxygenated rewarming of discarded donor kidneys

Kidney transplantation is considered the benchmark treatment for end-stage kidney disease patients. Nevertheless, the demand for donor kidneys is continuously on the rise and the scarcity of suitable kidneys poses a significant hindrance for patients and healthcare providers. One approach is to extend the criteria for the use of kidneys from deceased brain death and deceased circulatory death donors. Use of these organs especially from these extended criteria donors is associated with ischemia reperfusion injury (IRI) and resultant delayed graft function (DGF) as well as increased rates of allograft rejection. One approach to try to lessen these complications as well as increase the time the assessment of organ viability is the use of machine perfusion on recovered kidneys. In this study we obtained perfusates from discarded organs that had undergone Controlled Oxygenated Rewarming. Perfusates were analyzed for extracellular vesicles (EVs), dsDNA associated with EVs and microRNAs. These perfusates were then pumped over the Aethlon Hemopurifier, a plasma separator with an affinity resin containing the lectin Galanthus nivalis agglutinin (GNA). Following treatment with the Hemopurifier, a diminution in extracellular vesicles, dsDNA associated with EVs and microRNAs was observed. These results support a future study of the Aethlon Hemopurifier as part of a machine perfusion circuit to explore if the device decreases these mediators in a dynamic circuit and is associated with improved function of retrieved kidneys.

molecular biology↗