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Cosentino, M.

Publications and source records attributed to Cosentino, M..

3 recordsLinked to original sources

The COVID-19 RNA vaccine SpikevaxTM transfects human umbilical endothelial cells and induces Spike protein production, inflammation and leukocyte adhesion

Endothelial cell dysfunction plays a key role in the pathogenesis of severe and critical COVID-19, leading to a multi-systemic inflammatory disease, and results from the direct interaction of the SARS-CoV-2 Spike proteins with endothelial cells. COVID-19 RNA vaccines encode a recombinant SARS-CoV-2 Spike protein which undergoes systemic biodistribution. No information is however so far available on the direct effects of COVID-19 RNA vaccines on human endothelial cells. In the present study, we exposed cultured human umbilical venous endothelial cells (HUVEC) to the COVID-19 RNA vaccine SpikevaxTM (Moderna, Inc.), and thereafter we measured the expression of the Spike protein, of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-, of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as the attachment of human leukocytes to HUVEC layers. We also assessed the effects of SpikevaxTM on HUVEC viability. Exposure of HUVEC to the COVID-19 RNA vaccine SpikevaxTM resulted in effective cell transfection, and subsequent production of the Spike protein, which was expressed in the cells and secreted in the culture medium. Spike protein production was accompanied by increased gene expression of IL-6 and TNF- and of ICAM-1 and VCAM-1, as well as by increased attachment of leukocytes to HUVEC monolayers. Exposure to the COVID-19 RNA vaccine SpikevaxTM did not affect HUVEC viability. Our results provide a mechanistic explanation to post-COVID-19 RNA vaccination pathologies resulting from endothelial dysfunction, such as during atherosclerosis, autoimmune inflammation, and systemic inflammatory conditions.

pharmacology and toxicology↗

DeepVir: A reproducible workflow for large-scale viral dark matter discovery

High-throughput sequencing (HTS) has revolutionized virosphere exploration. However, characterizing highly divergent viral sequences remains a bottleneck known as Viral Dark Matter (VDM). Numerous tools were developed to unravel such diversity, but they usually require complex prior HTS data analysis processes. Consequently, a common bottleneck to VDM exploration is the manual, chained execution of complex command-line applications. To address the need for automated and scalable viral discovery, we developed DeepVir, a reproducible Snakemake pipeline that integrates classical homology-based alignments with profile Hidden Markov Model (HMM) mining of the RNA-dependent RNA polymerase (RdRp). To validate the pipelines efficacy, we analyzed 385.23 GB of publicly available transcriptomic data (203 Sequence Read Archive libraries) from 49 American bat species. DeepVir successfully identified 179 distinct viral groups. This included 903 contigs spanning nine known viral families, enabling the characterization of novel genomes within Orthomyxoviridae (Influenza A H7N9), Picornaviridae, Alphaflexiviridae, Retroviridae (Spumaretrovirinae), Papillomaviridae, Herpesviridae, and Adenoviridae. Furthermore, the pipeline uncovered 170 putative novel VDM lineages. By employing deep homology searches and Sequence Similarity Network (SSN) visualization, we contextualized these highly divergent VDM sequences, revealing significant evolutionary relationships with the orders Mononegavirales and Bunyavirales. Notably, human-driven curation of the pipelines outputs allowed for the cross-library assembly of the first putative exogenous Spumavirus in the Americas. Ultimately, by automating complex bioinformatic processing steps, scalable pipelines like DeepVir empower researchers to prioritize the biological and epidemiological interpretation of their findings, accelerating the characterization of wildlife virospheres and enhancing pathogen genomic surveillance.

bioinformatics↗

EFFECT OF A BIORESONANCE DEVICE ON VIABILITY AND METABOLIC ACTIVITY IN HUMAN UMBILICAL VENOUS ENDOTHELIAL CELLS

The present study was aimed at evaluating the effects of the bioresonance (BR)-based device QDOME MINI PERSONAL, produced by the society QMED SWISS SA (Lugano, CH), on the viability and mitochondrial metabolic activity of cultured human umbilical venous endothelial cells (HUVEC). To this end, HUVEC were cultured under standard conditions and exposed for 24 h to an "active" or to a mock BR device, in resting conditions and during treatment with H2O2 at the concentration of 500 M, added at the beginning of the 24 h period. The personnel who performed the experiments, collected, and analysed the data was unaware of which device was "active" and which was mock. At the end of the culture, HUVEC were harvested and evaluated for viability and mitochondrial metabolic activity by means of the Trypan Blue exclusion and the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide reduction method, respectively. Under control conditions, viability and mitochondrial metabolic activity were not different in HUVEC exposed to the "active" or to the mock device. HUVEC viability, however, was significantly reduced by exposure to H2O2 in samples exposed to the mock device but not in those exposed to the "active" device. HUVEC mitochondrial metabolic activity was significantly reduced by exposure to H2O2 in both samples exposed to the "active" and to the mock device, however reduction was significantly less in samples exposed to the "active" device. In conclusion, exposure to the BR-based device QDOME MINI PERSONAL, produced by the society QMED SWISS SA (Lugano, CH), prevented the H2O2-induced reduction of viability and reduced the H2O2-induced impairment of mitochondrial metabolic activity in cultured HUVEC.

cell biology↗