Universidade Federal de Ouro Preto

The association of genetic variants and environmental factors contribute to increased susceptibility to arterial hypertension (AH). Polymorphisms of the angiotensin-converting enzyme (ACE) gene have been identified as a genetic risk factor related to blood pressure (BP) levels and liver function, since they influence the renin-angiotensin-aldosterone system (RAAS).

To evaluate the influence of the rs4344 polymorphism of the ACE gene on AH and biochemical parameters of liver function (ALT, AST, GGT and ALP) in normotensive and hypertensive patients.

The identification of the polymorphism was performed by qPCR, using the TaqMan^® system, in 811 individuals (484 normotensive and 327 hypertensive) and biochemical dosages (AST, ALT, GGT and ALP) were performed by UV/Vis spectrophotometry. A univariate logistic regression model was used to identify factors associated with hypertension and Pearson's chi-square test to assess allele frequency between groups. A multivariate logistic regression model was used to correct confounding factors and assess the association of the variant with hypertension. Data normality was assessed using the Shapiro-Wilk test. Continuous nonparametric variables were expressed as median and interquartile range and analyzed using the Mann-Whitney test and parametric data were expressed as mean and standard deviation and analyzed by unpaired Student's t test. The rs4344 variant was not linked to hypertension in the individuals examined. However, concerning liver function marker enzymes, the G allele was associated with increased levels of GGT and ALT in hypertensive patients.

Our findings indicated that the rs4344 variant of the ACE gene is linked to impaired liver function in hypertensive individuals.

Isoflurane is a widely used inhaled anesthetic, but its administration has been linked to increased reactive oxygen species (ROS) and pro-inflammatory cytokines. NADPH oxidases are suggested as the primary ROS source. This study aimed to evaluate the mechanisms by which isoflurane induces ROS and reactive nitrogen species (RNS) in vitro in human and murine cells and in vivo using wild-type (WT) and NOX2 knockout (NOX2^-/-) mice.

J774A.1 macrophages and MRC-5 fibroblast were exposed to 2 % isoflurane or ambient air for 3 or 6 h. In vivo, 28 mice (WT and NOX2^-/-) were divided into four groups (n = 7/group) and exposed to 2 % isoflurane for 3 h.

Isoflurane significantly altered cell metabolism and increased ROS production. In vivo, ISOWT (12.42 ± 4.44); (10.19 ± 3.44) mice showed greater leukocyte and macrophage influx in bronchoalveolar lavage fluid (BALF) than WT controls (p < 0.05). Superoxide dismutase, catalase activity, and the expression of iNOS, IL-1β, NF-κB, and Nrf2 were significantly elevated in ISOWT mice compared to the control (p < 0.0411). Levels of CCL2, IL-1β, and IL-6 also increased in ISOWT compared to WT (p < 0.0391). However, no significant differences were found between NOX2^-/-isoflurane-exposed mice and their controls.

These findings demonstrate that the NADPH oxidase NOX2 plays a key role in oxidative stress and inflammation in the lungs of healthy mice exposed to isoflurane.

Diseases caused by parasites of the genus Leishmania are considered neglected infections. Visceral leishmaniasis (VL) is the most severe form of the disease, with a high annual incidence worldwide. In Brazil, dogs play an essential role as reservoirs, exhibiting a high concentration of parasites on their skin and no clinical signs, making them potential transmitters of the disease. Given the need for an efficient method to reduce the incidence of the disease, this study aimed to develop a gene encoding a chimeric protein with multiple epitopes that target both CD4⁺ and CD8⁺ T lymphocytes. Together with the MPLA adjuvant, the chimeric protein has the potential to compose a vaccine formulation against canine visceral leishmaniasis. Using an immunoinformatics analysis tool, the prediction of specific epitopes for CD4⁺ and CD8⁺ T lymphocytes was performed on sequences of hypothetical proteins previously identified in the immunoproteome of Leishmania (Leishmania) infantum parasites. The vaccine formulation was evaluated in Balb/c mice, and the chimeric protein, in association with the adjuvant, induced a protective response with a polarized T_H1 profile against the Leishmania parasite, characterized by high levels of IFN-γ, TNF-α, and low levels of IL-10. Additionally, the vaccinated animals showed a significant reduction in parasite burden in the liver, spleen, and bone marrow and draining lymph nodes of the paws compared to the control groups. Thus, the chimeric protein described here has the potential to be used in a vaccine formulation against canine leishmaniasis.