BackgroundMyeloproliferative neoplasms are Philadelphia chromosome-negative diseases characterized by hyperproliferation of mature myeloid cells, associated or not with the Janus kinase 2 tyrosine kinase mutation, JAK2V617F. As there is no curative therapy, researchers have been investigating new drugs to treat myeloproliferative neoplasms, including l-amino acid oxidase from Calloselasma rhodostoma snake venom (CR-LAAO), which is a toxin capable of eliciting apoptosis in several tumor cell lines.ObjectiveTo evaluate the effects of l-amino acid oxidase from C. rhodostoma snake venom in the apoptotic machinery of JAK2-mutated cell lines.MethodsThe HEL 92.1.7 and SET-2 cell lines were cultured with l-amino acid oxidase and catalase for 12 h at 37 °C in 5% carbon dioxide. The cell viability was assessed by the multi-table tournament method, the level of apoptosis was measured by flow cytometry, and the expression of cysteine-dependent aspartate-specific proteases and cleaved Poly(ADP-ribose) polymerase were analyzed by Western blotting.Resultsl-Amino acid oxidase from C. rhodostoma snake venom was cytotoxic to HEL 92.1.7 and SET-2 cells (50% inhibitory concentration = 0.15 μg/mL and 1.5 μg/mL, respectively) and induced apoptosis in a concentration-dependent manner. Cell treatment with catalase mitigated the l-amino acid oxidase toxicity, indicating that hydrogen peroxide is a key component of its cytotoxic effect.The activated caspases 3 and 8 expression and cleaved PARP in HEL 92.1.7 and SET-2 cells confirmed the apoptosis activation by CR-LAAO.Conclusionsl-Amino acid oxidase from C. rhodostoma snake venom is a potential antineoplastic agent against HEL 92.1.7 and SET-2 JAK2V617F-positive cells as it activates the extrinsic apoptosis pathway.
The coronavirus disease of 2019 , characterized as a pandemic by the World Health Organization in March 2020, has infected over 30.3 million people and caused 948,147 deaths globally, 134,935 of them in Brazil, as of September 18, 2020 [1]. It can lead to severe pulmonary disease, including pneumonia and acute respiratory distress syndrome (ARDS), and many extrapulmonary complications. These include thrombotic events and cardiovascular, neurological, renal, endocrine, hepatic, and gastrointestinal manifestations, as well as musculoskeletal, ocular, and dermatological symptoms [2]. In this chapter, we will overview some of these complications, reported until now, and some treatment-related and possible long-term sequelae.
COVID-19-Related Pulmonary ComplicationsUndoubtedly, the foremost feared complication related to COVID-19 is the development of respiratory failure due to lung involvement. Since the beginning of the pandemic, it has been evident that the mortality was directly related to a viral
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