Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients.

For over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent inosine increase in COVID-19 patients, while the nucleotides ATP and ADP had positive correlations with fibrinogen and other coagulation proteins. Also, ATP, ADP, inosine, and hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression, COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in COVID-19 patients. KEY MESSAGES : Adenosinergic pathways are modulated on leukocytes from COVID-19 patients. Plasmatic inosine levels are increased in COVID-19 patients. ATP, ADP, AMP, hypoxanthine, and inosine are correlated with coagulation players. The nucleotides and nucleosides are correlated with patients' clinical features. The P2 receptors and ectoenzymes are correlated with Tissue factor in COVID-19.

Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro.

Mesenchymal stem cells (MSCs) have recently been described to home to brain tumors and to integrate into the tumor-associated stroma. Understanding the communication between cancer cells and MSCs has become fundamental to determine whether MSC-tumor interactions should be exploited as a vehicle for therapeutic agents or considered a target for intervention. Therefore, we investigated whether conditioned medium from adipose-derived stem cells (ADSCs-CM) modulate glioma tumor cells by analyzing several cell biology processes in vitro. C6 rat glioma cells were treated with ADSCs-CM, and cell proliferation, cell cycle, cell viability, cell morphology, adhesion, migration, and expression of epithelial-mesenchymal transition (EMT)-related surface markers were analyzed. ADSCs-CM did not alter cell viability, cell cycle, and growth rate of C6 glioma cells but increased their migratory capacity. Moreover, C6 cells treated with ADSC-CM showed reduced adhesion and underwent changes in cell morphology. Up-regulation of EMT-associated markers (vimentin, MMP2, and NRAS) was also observed following treatment with ADSC-CM. Our findings demonstrate that the paracrine factors released by ADSCs are able to modulate glioma cell biology. Therefore, ADSC-tumor cell interactions in a tumor microenvironment must be considered in the design of clinical application of stem cell therapy. Graphical Abstract Factors released by adipose-derived stem cells (ADSCs) may modulate the biology of C6 glioma cells. When C6 cells are exposed to a conditioned medium from adipose-derived stem cells (ADSCs-CM), some of these cells can undergo an EMT-like process and trans-differentiate into cells with a more mesenchymal phenotype, characterized by enhanced expression of EMT-related surface markers, reduced cell adhesion capacity, increased migratory capacity, as well as changes in cell and nuclei morphology.