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Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 μg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product.

The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds\' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 ± 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 ± 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.

Chagas disease, discovered over a century ago, continues to pose a global health challenge, affecting millions mainly in Latin America. This historical review with commentary outlines the disease\'s discovery, its evolution into a global concern due to migration, and highlights significant advances in diagnostics and treatment strategies. Despite these advancements, the paper discusses ongoing challenges in eradication, including vector control, congenital transmission, the disease\'s asymptomatic nature, and socioeconomic barriers to effective management. It calls for a multidisciplinary approach, enhanced diagnostics, improved treatment accessibility, and sustained vector control efforts. The review emphasizes the importance of global collaboration and increased funding to reduce Chagas disease\'s impact.

UNASSIGNED: Trypanosoma cruzi is a protozoan parasite that causes the tropical ailment known as Chagas disease, which has its origins in South America. Globally, it has a major impact on health and is transported by insect vector that serves as a parasite. Given the scarcity of vaccines and the limited treatment choices, we conducted a comprehensive investigation of core proteomics to explore a potential reverse vaccine candidate with high antigenicity.
UNASSIGNED: To identify the immunodominant epitopes, T. cruzi core proteomics was initially explored. Consequently, the vaccine sequence was engineered to possess characteristics of non-allergenicity, antigenicity, immunogenicity, and enhanced solubility. After modeling the tertiary structure of the human TLR4 receptor, the binding affinities were assessed employing molecular docking and molecular dynamics simulations (MDS).
UNASSIGNED: Docking of the final vaccine design with TLR4 receptors revealed substantial hydrogen bond interactions. A server-based methodology for immunological simulation was developed to forecast the effectiveness against antibodies (IgM + IgG) and interferons (IFN-g). The MDS analysis revealed notable levels of structural compactness and binding stability with average RMSD of 5.03 Aring;, beta-factor 1.09e+5 Å, Rg is 44.7 Aring; and RMSF of 49.50 Aring;. This is followed by binding free energies calculation. The system stability was compromised by the complexes, as evidenced by their corresponding Gibbs free energies of -54.6 kcal/mol.
UNASSIGNED: Subtractive proteomics approach was applied to determine the antigenic regions of the T cruzi. Our study utilized computational techniques to identify B- and T-cell epitopes in the T. cruzi core proteome. In current study the developed vaccine candidate exhibits immunodominant features. Our findings suggest that formulating a vaccine targeting the causative agent of Chagas disease should be the initial step in its development.

Chagas disease is an inflammatory parasitic infection caused by Trypanosoma cruzi (T. cruzi). Early diagnosis is crucial in guiding treatment and slowing disease progression; however, current diagnostic methods have insufficient detection limits and often require skilled technicians. Molecular tests, especially isothermal nucleic acid assays, are advantageous due to their excellent sensitivity, specificity, speed, and simplicity. Here, we optimized a colorimetric loop-mediated isothermal amplification (LAMP) assay for T. cruzi. We can detect as few as 2 genomic copies/reaction using three different T. cruzi strains. We examined selectivity using other parasitic protozoans and successfully detected T. cruzi DNA extracted from parasites in human whole blood down to 1.2 parasite equivalents/reaction. We also performed a blinded study using canine blood samples and established a 100% sensitivity, specificity, and accuracy for the colorimetric LAMP assay. Finally, we used a heated 3D printer bed and an insulated thermos cup to demonstrate that the LAMP incubation step could be performed with accessible, low-cost materials. Altogether, we have developed a high-performing assay for T. cruzi with a simple colorimetric output that would be ideal for rapid, low-cost screening at the point of use.

The hematophagous common bed bug, Cimex lectularius, is not known to transmit human pathogens outside laboratory settings, having evolved various immune defense mechanisms including the expression of antimicrobial peptides (AMPs). We unveil three novel prolixicin AMPs in bed bugs, exhibiting strong homology to the prolixicin of kissing bugs, Rhodnius prolixus, and to diptericin/attacin AMPs. We demonstrate for the first time sex-specific and immune mode-specific upregulation of these prolixicins in immune organs, the midgut and rest of body, following injection and ingestion of Gr+ (Bacillus subtilis) and Gr- (Escherichia coli) bacteria. Synthetic CL-prolixicin2 significantly inhibited growth of E. coli strains and killed or impeded Trypanosoma cruzi, the Chagas disease agent. Our findings suggest that prolixicins are regulated by both IMD and Toll immune pathways, supporting cross-talk and blurred functional differentiation between major immune pathways. The efficacy of CL-prolixicin2 against T. cruzi underscores the potential of AMPs in Chagas disease management.

BACKGROUND: Monitoring and analysing the infection rates of the vector of Trypanosoma cruzi, that causes Chagas disease, helps assess the risk of transmission.
OBJECTIVE: A study was carried out on triatomine in the State of Paraná, Brazil, between 2012 and 2021 and a comparison was made with a previous study. This was done to assess the risk of disease transmission.
METHODS: Ecological niche models based on climate and landscape variables were developed to predict habitat suitability for the vectors as a proxy for risk of occurrence.
RESULTS: A total of 1,750 specimens of triatomines were recorded, of which six species were identified. The overall infection rate was 22.7%. The areas with the highest risk transmission of T. cruzi are consistent with previous predictions in municipalities. New data shows that climate models are more accurate than landscape models. This is likely because climate suitability was higher in the previous period.
CONCLUSIONS: Regardless of uneven sampling and potential biases, risk remains high due to the wide presence of infected vectors and high environmental suitability for vector species throughout the state and, therefore, improvements in public policies aimed at wide dissemination of knowledge about the disease are recommended to ensure the State remains free of Chagas disease.

Optical microscopy videos enable experts to analyze the motion of several biological elements. Particularly in blood samples infected with Trypanosoma cruzi (T. cruzi), microscopy videos reveal a dynamic scenario where the parasites\' motions are conspicuous. While parasites have self-motion, cells are inert and may assume some displacement under dynamic events, such as fluids and microscope focus adjustments. This paper analyzes the trajectory of T. cruzi and blood cells to discriminate between these elements by identifying the following motion patterns: collateral, fluctuating, and pan-tilt-zoom (PTZ). We consider two approaches: i) classification experiments for discrimination between parasites and cells; and ii) clustering experiments to identify the cell motion. We propose the trajectory step dispersion (TSD) descriptor based on standard deviation to characterize these elements, outperforming state-of-the-art descriptors. Our results confirm motion is valuable in discriminating T. cruzi of the cells. Since the parasites perform the collateral motion, their trajectory steps tend to randomness. The cells may assume fluctuating motion following a homogeneous and directional path or PTZ motion with trajectory steps in a restricted area. Thus, our findings may contribute to developing new computational tools focused on trajectory analysis, which can advance the study and medical diagnosis of Chagas disease.

In the subfamily Triatominae, the genus Rhodnius is one of the most studied, not only because of its epidemiological importance, but also because of the difficulty in differentiating its species. Currently, one of the strategies to control Chagas disease, besides other initiatives such as the analysis of donated blood, is focused on fighting the vector. Correctly identifying triatomines is essential for the entomoepidemiological surveillance of Chagas disease. The objective of the present work was to compare the species of the R.prolixus complex using geometric morphometry of hemelytra and heads to evaluate the patterns of intraspecific and interspecific allometry and their taxonomic implications. This method can help in the diagnosis of close species, whose morphological characteristics are insufficient for correct identification. Specimens from five different collections were used, covering the species included in the R.prolixus complex (R.barretti, R.dalessandroi, R.domesticus, R.marabaensis, R.milesi, R.montenegrensis, R.nasutus, R.neglectus, R.neivai, R.prolixus and R.robustus). Morphometric analyses indicated that the hemelytra are not structures with good resolution for separating species and, for this reason, the use of the heads proved to be more adequate for this group (thus allowing differentiation of all species of the R.prolixus complex). The results suggest that R.milesi is a variant of R.neglectus and confirms that R.prolixus and R.robustus are distinct species. Furthermore, we propose the creation of the R.neivai complex comprising R.domesticus and R.neivai.