Untargeted Metabolic Profiling of Extracellular Vesicles of SARS-CoV-2-Infected Patients Shows Presence of Potent Anti-Inflammatory Metabolites.

Extracellular vesicles (EVs) carry important biomolecules, including metabolites, and contribute to the spread and pathogenesis of some viruses. However, to date, limited data are available on EV metabolite content that might play a crucial role during infection with the SARS-CoV-2 virus. Therefore, this study aimed to perform untargeted metabolomics to identify key metabolites and associated pathways that are present in EVs, isolated from the serum of COVID-19 patients. The results showed the presence of antivirals and antibiotics such as Foscarnet, Indinavir, and lymecycline in EVs from patients treated with these drugs. Moreover, increased levels of anti-inflammatory metabolites such as LysoPS, 7-α,25-Dihydroxycholesterol, and 15-d-PGJ2 were detected in EVs from COVID-19 patients when compared with controls. Further, we found decreased levels of metabolites associated with coagulation, such as thromboxane and elaidic acid, in EVs from COVID-19 patients. These findings suggest that EVs not only carry active drug molecules but also anti-inflammatory metabolites, clearly suggesting that exosomes might play a crucial role in negotiating with heightened inflammation during COVID-19 infection. These preliminary results could also pave the way for the identification of novel metabolites that might act as critical regulators of inflammatory pathways during viral infections.

Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor ß (TGFß) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.