• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.435-437
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• 2019

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and is endemic in many Latin American countries. Diagnosis is based on serologic testing and the WHO recommends two or more serological tests for confirmation. Acidic ribosomal P protein of T. cruzi showed strong reactivity against positive sera of patients, and we cloned the protein after fragmenting it to enhance its antigenicity and solubility. Twelve positive sera of Chagas disease patients were reacted with the fragmented ribosomal P protein using western blot. Detection rate and density for each fragment were determined. Fragments F1R1, F1R2, and F2R1 showed 100% rate of detection, and average density scoring of 2.00, 1.67, and 2.42 from a maximum of 3.0, respectively. Therefore, the F2R1 fragment of the ribosomal P protein of T. cruzi could be a promising antigen to use in the diagnosis of Chagas disease in endemic regions with high specificity and sensitivity.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.386-394
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• 2019

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor ($P-elF2{\alpha}$) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

• Parasites, Hosts and Diseases
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• v.57 no.1
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• pp.39-41
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• 2019

In the indeterminate chronic period of Chagas disease (ChD) the treatment has not been conclusive, because the serological negativization requires many years. This study aims to evaluate the efficacy of nifurtimox (NF) in the treatment of chronic ChD in prolonged follow-up by serological techniques of indirect immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) IgG comparing 2 groups of patients, treated and non treated. Mann-Whitney test was performed for ELISA and IFA, with significant difference between the groups (P<0.05). IgG levels were lower in individuals treated compared with untreated patients, indicating chemotherapeutic efficacy in prolonged follow-up.

• Parasites, Hosts and Diseases
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• v.54 no.5
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• pp.585-590
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• 2016

Paleopathologists have begun exploring the pathoecology of parasitic diseases in relation to diet and environment. We are summarizing the parasitological findings from a mummy in the site of Lapa do Boquete, a Brazilian cave in the state of Minas Gerais. These findings in context of the archaeology of the site provided insights into the pathoecology of disease transmission in cave and rockshelter environments. We are presenting a description of the site followed by the evidence of hookworm, intestinal fluke, and Trypanosoma infection with resulting Chagas disease in the mummy discovered in the cave. These findings are used to reconstruct the transmission ecology of the site.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.288-294
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• 2010

Three dimensional quantitative-structure relationships (3D-QSARs) models between structures of phenoxy, phenylthio or benzyloxy substituted quinolone analogues and their antitrypanosomal activity against Chagas disease (Trypanosoma cruzi) were derived and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimized CoMFA 1 model ($q^2$=0.528 and $r^2$=0.964) showed the best statistical results. According to the optimized CoMFA 1 model, the antitrypanosomal activities were dependent on the steric (60.0%) and electrostatic (36.2%) factors of quinolone derivatives. From the contour maps, it is predicted that the activity will be increased when sterically favored groups were located in $R_4$ and $R_5$ position and sterically disfavored groups were located in $R_2$ position. Also, the positively charged groups on $R_2$ would be able to increase the antitrypanosomal activities.

• Parasites, Hosts and Diseases
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• v.56 no.5
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• pp.515-519
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• 2018

Triatoma rubrofasciata is a wide-spread vector of Chagas disease in Americas. In this study, we completed the mitochondrial genome sequencing of T. rubrofasciata. The total length of T. rubrofasciata mitochondrial genome was 17,150 bp with the base composition of 40.4% A, 11.6% G, 29.4% T and 18.6% C. It included 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and one control region. We constructed a phylogenetic tree on the 13 protein-coding genes of T. rubrofasciata and other 13 closely related species to show their phylogenic relationship. The determination of T. rubrofasciata mitogenome would play an important role in understanding the genetic diversity and evolution of triatomine bugs.

• Parasites, Hosts and Diseases
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• v.61 no.4
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• pp.405-417
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• 2023

Chagas disease, caused by Trypanosoma cruzi parasite, is a significant but neglected tropical public health issue in Latin America due to the diversity of its genotypes and pathogenic profiles. This complexity is compounded by the adverse effects of current treatments, underscoring the need for new therapeutic options that employ medicinal plant extracts without negative side effects. Our research aimed to evaluate the trypanocidal activity of Bidens pilosa fractions against epimastigote and trypomastigote stages of T. cruzi, specifically targeting the Brener and Nuevo León strains-the latter isolated from Triatoma gerstaeckeri in General Terán, Nuevo León, México. We processed the plant's aerial parts (stems, leaves, and flowers) to obtain a methanolic extract (Bp-mOH) and fractions with varying solvent polarities. These preparations inhibited more than 90% of growth at concentrations as low as 800 ㎍/ml for both parasite stages. The median lethal concentration (LC₅₀) values for the Bp-mOH extract and its fractions were below 500 ㎍/ml. Tests for cytotoxicity using Artemia salina and Vero cells and hemolytic activity assays for the extract and its fractions yielded negative results. The methanol fraction (BPFC3MOH1) exhibited superior inhibitory activity. Its functional groups, identified as phenols, enols, alkaloids, carbohydrates, and proteins, include compounds such as 2-hydroxy-3-methylbenzaldehyde (50.9%), pentadecyl prop-2-enoate (22.1%), and linalool (15.4%). Eight compounds were identified, with a match confirmed by the National Institute of Standards and Technology (NIST-MS) software through mass spectrometry analysis.

• Parasites, Hosts and Diseases
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• v.55 no.1
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• pp.81-84
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• 2017

Trypanosoma cruzi is the etiological agent of Chagas disease. Epimastigote forms of T. cruzi can be readily cultured in axenic conditions. Ethanol and dimethyl sulfoxide (DMSO) are commonly used solvents employed as vehicles for hydrophobic compounds. In order to produce a reference plot of solvent dependent growth inhibition for T. cruzi research, the growth of epimastigotes was analyzed in the presence of different concentrations of ethanol (0.1-4.0%) and DMSO (0.5-7.5%). The ability of the parasites to resume growth after removal of these solvents was also examined. As expected, both ethanol and DMSO produced a dose-dependent inhibition of cellular growth. Parasites could recover normal growth after 9 days in up to 2% ethanol or 5% DMSO. Since DMSO was better tolerated than ethanol, it is thus recommended to prefer DMSO over ethanol in the case of a similar solubility of a given compound.

• IMMUNE NETWORK
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• v.22 no.6
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• pp.51.1-51.20
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• 2022

Trypanosoma cruzi, the etiological agent of Chagas disease, is an intracellular protozoan parasite, which is now present in most industrialized countries. About 40% of T. cruzi infected individuals will develop severe, incurable cardiovascular, gastrointestinal, or neurological disorders. The molecular mechanisms by which T. cruzi induces cardiopathogenesis remain to be determined. Previous studies showed that increased IL-6 expression in T. cruzi patients was associated with disease severity. IL-6 signaling was suggested to induce pro-inflammatory and pro-fibrotic responses, however, the role of this pathway during early infection remains to be elucidated. We reported that T. cruzi can dysregulate the expression of host PIWI-interacting RNAs (piRNAs) during early infection. Here, we aim to evaluate the dysregulation of IL-6 signaling and the piRNAs computationally predicted to target IL-6 molecules during early T. cruzi infection of primary human cardiac fibroblasts (PHCF). Using in silico analysis, we predict that piR_004506, piR_001356, and piR_017716 target IL6 and SOCS3 genes, respectively. We validated the piRNAs and target gene expression in T. cruzi challenged PHCF. Secreted IL-6, soluble gp-130, and sIL-6R in condition media were measured using a cytokine array and western blot analysis was used to measure pathway activation. We created a network of piRNAs, target genes, and genes within one degree of biological interaction. Our analysis revealed an inverse relationship between piRNA expression and the target transcripts during early infection, denoting the IL-6 pathway targeting piRNAs can be developed as potential therapeutics to mitigate T. cruzi cardiomyopathies.