Coronavirus disease 2019 (COVID-19) is driven by dysregulated immune responses yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 47 patients with confirmed SARS-CoV-2 infection and 16 uninfected controls, we found an immunometabolic dysregulation specific for patients with progressed disease that was reversible in the recovery phase. Specifically, T cells and monocytes exhibited increased mitochondrial mass, accumulated intracellular ROS and these changes were accompanied by disrupted mitochondrial architecture. Basigin (CD147), but not established markers of T cell activation, was up-regulated on T cells from progressed COVID-19 patients and correlated with ROS accumulation, reflected in the transcriptome. During recovery, basigin and ROS decreased to match the uninfected controls. In vitro analyses confirmed the correlation and showed a down-regulation of ROS by dexamethasone treatment. Our findings provide evidence of a basigin-related and reversible immunometabolic dysregulation in COVID-19.
Leishmaniasis and Chagas diseases are two of the most important parasitic diseases in the world. Both belong to the category of Neglected Tropical Diseases, and they cannot be prevented by vaccination. Their treatments are founded in outdated drugs that possess many pernicious side-effects and they're not easy to administer. With the aim of discovering new compounds that could serve as anti-trypanosomal drugs, an antiparasitic study of a synthetic compound family has been conducted. A series of new 1,4-bis(alkylamino)-and 1alkylamino-4-chloroazine and benzoazine derivatives 1-4 containing imidazole rings have been synthesized and identified.Their structures showed a possible interest based on previous work. Their in vitro anti-Leishmania infantum, anti-L. braziliensis, anti-L. donovani and anti-T. cruzi activity were tested, as well as the inhibition of Fe-SOD enzymes. It was found that some of them exhibited quite relevant values indicative of being worthy of future more detailed studies, as most of them showed activity to more than only one parasite species, especially compound 3 c was active for the three studied Leishmania species and also for T. cruzi, which is a very interesting trait as it covers a wide spectrum.
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