Obesity is a strong risk factor for short-term mortality and adverse outcomes in Mexican patients with COVID-19: a national observational study.

Conflicting results have been obtained through meta-analyses for the role of obesity as a risk factor for adverse outcomes in patients with coronavirus disease-2019 (COVID-19), possibly due to the inclusion of predominantly multimorbid patients with severe COVID-19. Here, we aimed to study obesity alone or in combination with other comorbidities as a risk factor for short-term all-cause mortality and other adverse outcomes in Mexican patients evaluated for suspected COVID-19 in ambulatory units and hospitals in Mexico. We performed a retrospective observational analysis in a national cohort of 71 103 patients from all 32 states of Mexico from the National COVID-19 Epidemiological Surveillance Study. Two statistical models were applied through Cox regression to create survival models and logistic regression models to determine risk of death, hospitalisation, invasive mechanical ventilation, pneumonia and admission to an intensive care unit, conferred by obesity and other comorbidities (diabetes mellitus (DM), chronic obstructive pulmonary disease, asthma, immunosuppression, hypertension, cardiovascular disease and chronic kidney disease). Models were adjusted for other risk factors. From 24 February to 26 April 2020, 71 103 patients were evaluated for suspected COVID-19; 15 529 (21.8%) had a positive test for SARS-CoV-2; 46 960 (66.1%), negative and 8614 (12.1%), pending results. Obesity alone increased adjusted mortality risk in positive patients (hazard ratio (HR) = 2.7, 95% confidence interval (CI) 2.04-2.98), but not in negative and pending-result patients. Obesity combined with other comorbidities further increased risk of death (DM: HR = 2.79, 95% CI 2.04-3.80; immunosuppression: HR = 5.06, 95% CI 2.26-11.41; hypertension: HR = 2.30, 95% CI 1.77-3.01) and other adverse outcomes. In conclusion, obesity is a strong risk factor for short-term mortality and critical illness in Mexican patients with COVID-19; risk increases when obesity is present with other comorbidities.

Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1ß, IL-12p70 and IL-10 in human macrophages.

Leishmania major : detection of membrane-bound protein tyrosine phosphatase.

PTPases have been reported as a virulence factor in different pathogens. Recent studies suggest that PTPases play a role in the pathogenesis of Leishmania infections through activation of macrophage PTPases by the parasite. We report here the presence of a membrane-bound PTPase in Leishmania major promastigotes. We detected differences in the PTPases present in the procyclic and metacyclic stages of promastigotes. In metacyclic promastigotes, the PTPase activity was totally inhibited by specific PTPase and serine/threonine inhibitors, whereas in procyclic promastigotes the PTPase activity was inhibited only with PTPase inhibitors. Two antibodies against the catalytic domains of the human placental PTPase1B and a PTPase from Trypanosoma brucei cross-reacted with a 55-60 kDa molecule present in the soluble detergent-extracted fraction of a Leishmania homogenate. Metacyclic promastigotes expressed more of this molecule than parasites in the procyclic stage. Yet the specific activity of the enzyme was lower in metacyclic than in procyclic promastigotes. Ultrastructural localization of the enzyme showed that it was more membrane-associated in metacyclic promastigotes, whereas in procyclic promastigotes it was scattered throughout the cytoplasm. This is the first demonstration of a PTPase present in Leishmania major promastigotes that differs in expression, activity and ultrastructural localization between the procyclic and metacyclic stages of the parasite's life-cycle.

Membrane-bound acid phosphatase (MAP) from Entamoeba histolytica has phosphotyrosine phosphatase activity and disrupts the actin cytoskeleton of host cells.

Protein tyrosine phosphatases (PTPases) have been described as virulence factors in different pathogenic microorganisms. The pathogenic process by Enatamoeba histolytica is a multifactorial phenomenon that occurs in 3 steps: adhesion, cytolytic and cytotoxic effect, and phagocytosis. Lytic enzymes may participate during the second part of this process. In this work, we determined that purified membrane-bound acid phosphatase (MAP) from E. histolytica trophozoites has PTPase activity. The enzyme specifically dephosphorylated O-phospho-L-tyrosine at optimum pH of 5.0, with little activity towards O-phospho-L-serine, O-phospho-L-threonine, and ATP. It was inhibited by ammonium molybdate and sodium tungstate, and trifluoperazine did not show any effect. A monoclonal antibody against the catalytic domain of the human placental PTPase 1B, cross-reacted with a 55 kDa molecule present in the solubilized fraction. The interaction of the amoebic PTPase with HeLa cells resulted in the alteration of the cell actin cytoskeleton by disruption of the actin stress fibres.

Purification and properties of an acid phosphatase from Entamoeba histolytica HM-1:IMSS.

Entamoeba histolytica contains and secretes acid phosphatase, which has been proposed as a virulence factor in some pathogenic microorganisms. In this work, we purified and characterised a membrane-bound acid phosphatase (MAP) from E. histolytica HM-1:IMSS and studied the effect of different chemical compounds on the secreted acid phosphatase and MAP activities. MAP purification was accomplished by detergent solubilisation, and affinity and ion exchange chromatographies. The enzyme showed a pI of 5.5-6.2, an optimum pH of 5.5, and a Km value of 1.14 mM with p-nitrophenyl phosphate.