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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.

Head and neck cancer (HNC) comprises a spectrum of neoplasms that affect the upper aerodigestive tract and are the sixth most common cancers worldwide. Individuals with HNC exhibit various symptoms and metabolic changes, including immune alterations and alterations of the purinergic pathway, which may signal worse outcomes. Therefore, the purpose of this research was to measure the activity of purinergic ectoenzymes and interleukins in patients with HNC, oral cavity cancer, and larynx cancer.We recruited 32 patients and 33 healthy control subjects and performed the laboratory analyses. We identified dysregulation in the purinergic signaling pathway characterized by an increase in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and a decrease in the deamination of adenosine to inosine in these cancers (p 0.05). These alterations were likely caused by increased activity of the ectoenzymes E-NTPDase and ecto-5'-nucleotidase and reduced adenosine deaminase activity. This dysregulation was associated with immune alterations, increased levels of IL-10, and decreased myeloperoxidase activity (p 0.05), suggesting immunosuppression in these patients and suggesting possible accumulation of adenosine in the extracellular environment.Adenosine is a potent immunosuppressive molecule associated with tumor progression and immune evasion. Our findings suggest a relationship between extracellular purines and the development and progression of the tumor microenvironment and poor outcomes. These findings increase the understanding of biological mechanisms related to HNC and demonstrate that these components are potential diagnostic markers and therapeutic targets for future management strategies and improvement in the quality of life.

Made available in DSpace on 2022-04-29T08:37:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Universidade Estadual Paulista (1) Background: Intermittent fasting is a nutrition practice in which individuals fast for several hours in a day, mainly with feeding time during the daylight hours. They seek to improve metabolic performance and cellular resistance to stress. In this study, we tested the fasting protocol to investigate the glycemic effect in a laparotomy perioperative period in diabetic rats and histopathologic findings. (2) Methods: The animals were diabetic-induced with alloxan. Two groups were set according to the feeding protocol: free food and intermittent fasting, whose rats could only eat 8 h in the daylight. Both groups were anesthetized, and a laparotomy was performed. We evaluated the glucose levels during the perioperative period, and we accessed organ histology seeking damage of kidney, bowel and liver after surgical trauma, and we evaluated the wound healing process. (3) Results: Glycemic levels were improved in the intermittent fasting group, especially in the post-operative period after laparotomy. Comparing both groups’ tubular damage showed interdependency with mice with worse glycemic level (Z = 2.3; p = 0.0215) and wound-healing parameters showed interdependency with rats with better glycemic status for neovascularization (Z = 2.2; p = 0.0273) and the presence of sebaceous and sweat gland in the healing process (Z = 2.30; p = 0.0215). (4) Conclusions: Intermittent fasting before surgery can be a tool to improve glycemic levels in diabetic rats, with improvement especially in the post-operative period. Anesthesia Department São Paulo State University (UNESP)-Botucatu Medical School Pharmacology and Histology Department Integrated Regional University (URI) Academic Coordination Biomedical Sciencies Department Federal University of Fronteira Sul Postgraduate Program in Biochemistry Department Federal University of Santa Catarina Anesthesia Department São Paulo State University (UNESP)-Botucatu