A biomarker for tegumentary and visceral leishmaniasis based on a recombinant Leishmania hypothetical protein

The measures for leishmaniasis control include the precise diagnosis of disease. However, although several recombinant antigens have been tested with this biotechnological purpose, no effective product exists, which could detects patients with the active disease, as well as differentiates them from cured and treated patients. In this study, a conserved Leishmania hypothetical protein, which was identified in Leishmania infantum parasites, but evaluated to presents high homology in the amino acid sequences between distinct parasite species, was evaluated for the diagnosis of tegumentary and visceral leishmaniasis. In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant. Regarding the serological analyses, ELISA experiments using the recombinant protein (rLiHyL) and a human serological panel revealed high sensitivity and specificity values to detect both diseases, while control antigens showed worst results. Regarding the cellular response, results showed that rLiHyL-stimulated cells produced higher IFN-γ and lower IL-4 and IL-10 levels in the supernatants. Also, the anti-protein antibody production was evaluated in these patients, and data showed higher IgG2 and lower IgG1 levels found in the treated patients and healthy controls, demonstrating the stimulation of a Th1-type response induced by the rLiHyL protein. In conclusion, this hypothetical protein can be considered as antigenic in TL and VL, as well as a vaccine candidate to be tested in future studies to protect against disease.     

Effects of the Interaction of the ANKK1/DRD2 TaqIA and HTR2C Cys23Ser Polymorphisms on Approach Motivation in Schizophrenia Patients and Healthy People

Neuroscience and Behavioral Physiology - Objective. To assess the association of the DRD2 gene and its interaction with the HTR2C gene with the characteristics of the hedonistic and activatory...     

Association of Chronotype,Road Traffic Accidents,and Polymorphisms in Genes Linked with the Biological Clock and the Dopaminergic System

Neuroscience and Behavioral Physiology - Objective. To study the association between single-nucleotide polymorphisms (SNP) of the RORA (rs1159814), CLOCK (rs12649507), PER3 (rs2640909), NPSR1...     

The Role of Stretch-Activated Channels in Mediating mTORC1 Signaling in Isolated Rat Soleus Muscle in Response to Mechanical Stimulation after Functional Unloading

Neuroscience and Behavioral Physiology - The aim of the present work was to identify the role of stretch-activated ion channels (SAC) in the transmission of mechanical signals to the key...     

Learning with Reinforcement: the Role of Immediate Feedback and the Internal Model of the Situation

Neuroscience and Behavioral Physiology - Human behavior in conditions of partial indeterminacy of the outcome is characterized by correspondence between the frequency of actions and the probability...     

Comparative Characteristics of the Expression of Inducible NO Synthase in the Hippocampus of Humans and Experimental Animals

Neuroscience and Behavioral Physiology - Objective: To study the characteristics of the expression of inducible NO synthase (iNOS) in hippocampal fields CA1 and CA3 in adult male humans and adult...     

Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β, in the cervical microenvironment of HPV-infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF-β markers, and the expression of GITR and IL-10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25⁺FOXP3⁺, CD4⁺TGFβ⁺, IL-10⁺, and GITR⁺ cells in samples with high viral loads and severe lesions of HPV-infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation.