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Keywords = Chagas patients

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14 pages, 359 KiB  
Article
Association Between Physical Activity, Sedentary Time, and Quality of Life in Patients with Chagas Disease During COVID-19 Pandemic in Brazil: A Cross-Sectional Study
by Isis Gabrielli Gomes Xavier, Patrícia Mello Andrade, Rodrigo de Lima Vitor, Tayná Cruz Barros, Whesley Tanor Silva, Luciana Fernandes Portela, Marcelo Teixeira de Holanda, Luiz Henrique Conde Sangenis, Gilberto Marcelo Sperandio da Silva, Flavia Mazzoli-Rocha, Fernanda de Souza Nogueira Sardinha Mendes, Andréa Rodrigues da Costa, Marcelo Carvalho Vieira, Daniela Palheiro Mendes de Almeida, Cláudia Maria Valete, Alejandro Marcel Hasslocher-Moreno, Henrique Silveira Costa, Vitor Barreto Paravidino, Tatiana Rehder Gonçalves, Roberto Magalhães Saraiva and Mauro Felippe Felix Medianoadd Show full author list remove Hide full author list
Int. J. Environ. Res. Public Health 2025, 22(7), 1137; https://doi.org/10.3390/ijerph22071137 - 18 Jul 2025
Viewed by 303
Abstract
Background: COVID-19 led to social isolation, potentially reducing physical activity (PA), increasing sedentary time, and lowering quality of life (QoL). This study investigated the association between these factors in patients with Chagas disease (ChD) during the pandemic. Methods: This cross-sectional study included 187 [...] Read more.
Background: COVID-19 led to social isolation, potentially reducing physical activity (PA), increasing sedentary time, and lowering quality of life (QoL). This study investigated the association between these factors in patients with Chagas disease (ChD) during the pandemic. Methods: This cross-sectional study included 187 patients with ChD. PA and sedentary time were assessed by the IPAQ-short and QoL by the WHOQOL-Bref. The relationship between PA levels and sedentary time with QoL were assessed using unadjusted and adjusted generalized linear models. Results: The highest tertile of total PA was positively associated with the psychological (Exp β = 1.11; 95% CI: 1.02–1.22) and environmental (Exp β = 1.12; 95% CI: 1.01–1.23) QoL domains. The intermediate (Exp β = 1.12; 95% CI: 1.01–1.25) and highest (Exp β = 1.14; 95% CI: 1.02–1.27) tertiles of moderate-to-vigorous PA were positively associated with the physical domain. Similarly, both the intermediate (Exp β = 1.11; 95% CI: 1.01–1.22) and highest (Exp β = 1.12; 95% CI: 1.01–1.21) tertiles of moderate-to-vigorous PA were positively associated with the psychological domain. The highest tertile of sedentary time was associated with a decrease in the physical domain (Exp β = 0.88; 95% CI: 0.79–0.98). Conclusions: Higher levels of total and moderate-to-vigorous PA were associated with better QoL, while greater sedentary time was associated with poorer QoL. Full article
12 pages, 552 KiB  
Article
Impact of Kidney Function on the Survival of Patients with Chagas Cardiomyopathy and Implantable Cardioverter Defibrillators
by Fernanda Pinheiro Martin Tapioca, Luiz Carlos Santana Passos, Caio Cafezeiro, Willian Carvalho, Paulo Novis Rocha and Maria Gabriela Guimarães
J. Clin. Med. 2025, 14(14), 4862; https://doi.org/10.3390/jcm14144862 - 9 Jul 2025
Viewed by 366
Abstract
Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients [...] Read more.
Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients with Chagas cardiomyopathy (CC) have been underrepresented. This study aimed to determine whether kidney dysfunction has the same negative impacts on patients with ICDs or CRT-Ds and CC. Methods: We prospectively followed patients with CC and left ventricular ejection fractions (LVEFs) of ≤40% who underwent ICD or CRT-D implantation and had at least one prior creatinine measurement. The primary outcome was the survival rate during follow-up. Variables with a p of <0.10 from the univariate analysis were selected for inclusion in the Cox regression model. Results: A total of 343 patients were enrolled, with a median follow-up duration of 777 days. The mean age was 60.2 (±11.2) years. Fifty percent of patients were observed to have a New York Heart Association (NYHA) functional class of III, and the median left ventricular ejection fraction (LVEF) was 27% (22–32). Overall mortality events occurred in 113 (32.9%) participants during follow-up. Although the estimated glomerular filtration rate (eGFR) was significantly associated with survival in the univariate analysis [HR 0.98 (CI 95% 0.98–0.99), p = 0.007], it did not retain significance in the multivariate model [HR 0.99 (0.98–1.00), p = 0.138], which was adjusted for age, gender, atrial fibrillation (AF), body mass index (BMI), and the use of digoxin, furosemide, anticoagulants, and LVEF. Conclusions: Unlike other cardiomyopathies, impaired eGFR was not an independent predictor of mortality in this cohort of CC patients undergoing ICD or CRT-D implantation, possibly due to the distinctive pathophysiological mechanisms of the disease. These findings suggest that clinicians should not be discouraged from recommending CIEDs in patients with CC and moderately impaired kidney function, although further studies are warranted to assess outcomes in those with advanced CKD. Full article
(This article belongs to the Section Nephrology & Urology)
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16 pages, 421 KiB  
Article
Chagas Disease in a Non-Endemic Setting: Clinical Profile, Treatment Outcomes, and Predictors of Cure in a 15-Year Cohort Study
by Carlos Bea-Serrano, Ana Isabel de Gracia-León, Jara Llenas-García, Sara Vela-Bernal, Andreu Belmonte-Domingo, Carolina Pinto-Pla, Ana Ferrer-Ribera, María José Galindo, María Jesús Alcaraz and María Rosa Oltra Sempere
Trop. Med. Infect. Dis. 2025, 10(6), 161; https://doi.org/10.3390/tropicalmed10060161 - 11 Jun 2025
Viewed by 1475
Abstract
This retrospective cohort study aimed to assess clinical and epidemiological characteristics, treatment outcomes, and predictors of serological cure in patients with chronic Chagas disease in a non-endemic setting. All individuals aged ≥16 years with confirmed infection and evaluated at a tertiary hospital in [...] Read more.
This retrospective cohort study aimed to assess clinical and epidemiological characteristics, treatment outcomes, and predictors of serological cure in patients with chronic Chagas disease in a non-endemic setting. All individuals aged ≥16 years with confirmed infection and evaluated at a tertiary hospital in Spain from 2008 to 2023 were included. Most of the 107 participants were women (78.5%) and Bolivian-born (99.1%). Digestive and cardiac involvement were identified in 32.7% and 17.8% of cases, respectively. Cardiac symptoms were significantly associated with the diagnostic findings of cardiac involvement (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.1–8.2), whereas digestive symptoms did not correlate with imaging abnormalities (OR 0.7, 95% CI 0.3–1.6). Antiparasitic treatment, usually benznidazole, was initiated in 69% of patients and led to adverse events in 66.2%, with treatment discontinuation in 25.7%. Only 8.1% of treated patients achieved serological cure after a median 26 months, with obesity emerging as the only independent predictor (adjusted OR 31.0, 95% CI 3.7–261.2). Cardiac progression occurred in 9.3% of patients despite treatment. Although 59.8% were lost to follow-up, the cohort maintained a median follow-up of 27 months. These findings underscore the need for improved treatment strategies and sustained clinical monitoring in non-endemic settings. Full article
(This article belongs to the Special Issue Advances in Parasitic Neglected Tropical Diseases)
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31 pages, 4011 KiB  
Review
Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases
by Jaime A. Isern, Renzo Carlucci, Guillermo R. Labadie and Exequiel O. J. Porta
Trop. Med. Infect. Dis. 2025, 10(5), 142; https://doi.org/10.3390/tropicalmed10050142 - 20 May 2025
Cited by 1 | Viewed by 954
Abstract
Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, [...] Read more.
Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide–alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases. Full article
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18 pages, 2025 KiB  
Article
Immunogenicity of Trypanosoma cruzi Multi-Epitope Recombinant Protein as an Antigen Candidate for Chagas Disease Vaccine in Humans
by Christian F. Teh-Poot, Andrea Alfaro-Chacón, Landy M. Pech-Pisté, Miguel E. Rosado-Vallado, Oluwatoyin Ajibola Asojo, Liliana E. Villanueva-Lizama, Eric Dumonteil and Julio Vladimir Cruz-Chan
Pathogens 2025, 14(4), 342; https://doi.org/10.3390/pathogens14040342 - 3 Apr 2025
Viewed by 1101
Abstract
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the most significant neglected tropical disease affecting individuals in the Americas. Currently, available drugs, such as nifurtimox and benznidazole (BZN), are both toxic and ineffective in the chronic phase of [...] Read more.
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the most significant neglected tropical disease affecting individuals in the Americas. Currently, available drugs, such as nifurtimox and benznidazole (BZN), are both toxic and ineffective in the chronic phase of the disease. A promising alternative is the development of a Chagas disease vaccine, although this effort is hampered by the complexity of the parasite and HLA polymorphisms. In addition, the activation of epitope-specific CD8+ T cells is critical to conferring a robust cell-mediated immune response and protection by producing IFN-γ and perforin. Thus, the antigen (s) for the development of a Chagas vaccine or immunotherapy must include CD8+ T cell epitopes. In this study, we aimed to develop a multi-epitope recombinant protein as a novel human vaccine for Chagas disease. Sixteen database programs were used to predict de novo 40 potential epitopes for the HLA-A*02:01 allele. Nine out of the 40 predicted epitopes were able to elicit IFN-γ production in Peripheral Blood Mononuclear Cells (PBMCs) from Chagas patients. Molecular docking revealed a good binding affinity among the epitopes with diverse HLA molecules. Therefore, a recombinant multi-epitope protein including these nine T. cruzi CD8+ epitopes was expressed and demonstrated to recall an antigen-specific immune response in ex-vivo assays using PBMCs from Chagas patients with the HLA-A*02 allele. These findings support the development of this multi-epitope protein as a promising candidate human vaccine against Chagas disease. Full article
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17 pages, 4425 KiB  
Article
Epidemiological Scenario of American Trypanosomiasis and Its Socioeconomic and Environmental Relations, Pará, Eastern Brazilian Amazon
by Claudia do Socorro Carvalho Miranda, Bruna Costa de Souza, Tainara Carvalho Garcia Miranda Filgueiras, João Simão de Melo Neto, Amanda Sophia Carvalho Miranda da Silva, Hilton Pereira da Silva, Marcos Valério Santos da Silva, Frederico Itã Mateus Carvalho Oliveira Miranda, Edilene do Socorro Nascimento Falcão Sarges, Sérgio Luiz Althoff, Selma Kazumi da Trindade Noguchi and Nelson Veiga Gonçalves
Trop. Med. Infect. Dis. 2025, 10(4), 88; https://doi.org/10.3390/tropicalmed10040088 - 28 Mar 2025
Viewed by 750
Abstract
Chagas disease is a serious public health problem worldwide. In Brazil, the state of Pará has the largest number of reported cases. This article analyzes the spatial distribution of this disease and its relationship with socioeconomic, environmental, and public policy health variables in [...] Read more.
Chagas disease is a serious public health problem worldwide. In Brazil, the state of Pará has the largest number of reported cases. This article analyzes the spatial distribution of this disease and its relationship with socioeconomic, environmental, and public policy health variables in three mesoregions in the Pará state from 2013 to 2022. This ecological study used secondary data obtained from official Brazilian agencies. Spatial analysis was carried out using the flow, kernel, and bivariate global Moran techniques expressed in thematic maps. A total of 3664 cases of the disease were confirmed, with the highest number of cases being reported in the northeast of Pará. A seasonal pattern of the disease, an epidemiological profile similar to other diseases in the Amazon region, and the spatial dependence between the disease prevalence and socioeconomic indicators were observed. The most intense movement of patients for treatment was to the Belém metropolitan mesoregion, which has the majority of the health services and professionals. The disease showed an inhomogeneous pattern of cases in terms of the spatial distribution, with a direct relationship between areas with a higher number of cases and those with human clusters. The socioenvironmental origins of the disease transcend mesoregion boundaries and stem from the historically unsustainable development model in the Amazon. Full article
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8 pages, 567 KiB  
Article
TP53 Mutations in Chagasic Megaesophagus
by Aparecida Perpetuo Fedossi Silveira, Ricardo Quiterio Sartori, Lilian Castiglioni, Heidi Lacerda Alves da Cruz, Eumildo de Campos Junior, Cinara Cássia Brandão and Luiz Carlos de Mattos
Curr. Issues Mol. Biol. 2025, 47(4), 229; https://doi.org/10.3390/cimb47040229 - 27 Mar 2025
Viewed by 473
Abstract
Patients carrying Chagasic megaesophagus (CME) are at high risk for esophageal carcinoma. We aimed to investigate mutations in the TP53 in patients carrying CME. Blood samples from 114 patients with Chagas disease (CD) were used. The samples were subjected to PCR-SSCP analysis and [...] Read more.
Patients carrying Chagasic megaesophagus (CME) are at high risk for esophageal carcinoma. We aimed to investigate mutations in the TP53 in patients carrying CME. Blood samples from 114 patients with Chagas disease (CD) were used. The samples were subjected to PCR-SSCP analysis and DNA sequencing in exons 5 and 7 of the TP53 gene. We observed mutations in the exon 5 codon 184 (GAT > AAT) in 14.8% of G1 (11/74), 10% of G2 (4/40), and 5% of G3 (2/40). We also observed the codon 185 mutation (AGC > AGG) in 14.8% of G1 (11/74), 10% of G2 (4/40), and 7.5% of G3 (3/40). Regarding Exon 7, a mutation (G > T) was observed in the intronic region in 2.7% of G1 (2/74), 7.5% of G2 (3/40), and none of G3 (0/40). Our study showed, for the first time, simultaneous mutations at codons 184 and 185 of the TP53 gene in patients with CME and Chagasic patients without megaesophagus. More studies are needed to assess whether the simultaneous presence of mutations at codons 184 and 185 increases the risk of developing esophageal carcinoma in these patients. Full article
(This article belongs to the Collection Molecular Mechanisms in Human Diseases)
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30 pages, 3776 KiB  
Article
Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and Trypanosoma cruzi Amastigotes
by Gabriela Alves de Souza, Lorrane de Souza Chaves, Afonso Santine M. M. Velez, Jorge Lucas F. Lacerda, Paulo Pitasse-Santos, Jayane Clys Conceição dos Santos, Otávio Augusto Chaves, Carlos Serpa, Raphael do Carmo Valente, Leonardo Marques da Fonseca , Marcos André Rodrigues da Costa Santos, Jhenifer Santos dos Reis, Carlos Antônio do Nascimento Santos, Lucia Mendonça-Previato, Jose Osvaldo Previato, Celio Geraldo Freire-de-Lima, Debora Decoté-Ricardo, Leonardo Freire-de-Lima and Marco Edilson Freire de Lima
Pharmaceuticals 2025, 18(4), 456; https://doi.org/10.3390/ph18040456 - 24 Mar 2025
Cited by 1 | Viewed by 875
Abstract
Background: Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. In a similar context, [...] Read more.
Background: Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. In a similar context, the treatment of Chagas disease, a neglected tropical illness, is hindered by the high toxicity of the currently available drugs. Researchers are increasingly focusing on the development of safer and more selective alternatives, with natural compounds being studied as potential starting points for the creation of more effective drug candidates with a favorable therapeutic index. Objectives: The aim of this study was to design simplified curcumin-derived structures that preserved or enhanced their therapeutic activity against human lung cancer cell lines and T. cruzi, while also improving bioavailability and minimizing toxicity. Methods: In this study, curcumin and two natural curcuminoids inspired the synthesis of a chalcone and a set of bis-chalcones, compound classes known for their enhanced stability compared with their natural parent derivatives. The synthetic strategy used was the acid-catalyzed aldol condensation reaction. The stability profiles, IC50 values against A549 and H460 tumor cell lines, and trypanocidal activity against T. cruzi amastigotes of these derivatives were assessed. Results: The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC50 values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against T. cruzi amastigotes. Conclusions: This study provides a potential pathway toward the development of more effective and less toxic treatments for both cancer and Chagas disease. The simplified curcumin derivatives represent a promising foundation for designing new therapeutic agents with improved bioavailability and efficacy. Full article
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10 pages, 836 KiB  
Article
Prevalence, Molecular Epidemiology, and Clinical Characteristics of Human Bocavirus Among Patients with Acute Gastroenteritis in Northern Brazil During 2017–2022
by Yasmim Gabrielly Souza Sousa, Carolina Alcântara Maneschy, Carolina Costa Monteiro, João Victor Souza Rodrigues, Patrícia Santos Lobo, Dielle Monteiro Teixeira, Jones Anderson Monteiro Siqueira, Kenny Costa Pinheiro, Hugo Reis Resque, Luciana Damascena Silva, Sylvia Fátima dos Santos Guerra and Luana Silva Soares
Viruses 2025, 17(1), 79; https://doi.org/10.3390/v17010079 - 9 Jan 2025
Viewed by 919
Abstract
Acute gastroenteritis (AG) is a major illness in early childhood. Recent studies suggest a potential association between human bocavirus (HBoV) and AG. HBoV, a non-enveloped virus with a single-strand DNA genome, belongs to the Parvoviridae family. This study aimed to describe the frequency [...] Read more.
Acute gastroenteritis (AG) is a major illness in early childhood. Recent studies suggest a potential association between human bocavirus (HBoV) and AG. HBoV, a non-enveloped virus with a single-strand DNA genome, belongs to the Parvoviridae family. This study aimed to describe the frequency of HBoV in Northern Brazil using samples from patients with AG collected between 2017 and 2022. Fecal samples obtained from the viral gastroenteritis surveillance network at the Evandro Chagas Institute (IEC) were analyzed. Fecal suspensions (20%) were prepared, and the viral genome was extracted. PCR and nested-PCR were employed to detect HBoV, followed by nucleotide sequencing to identify viral types. Out of 692 samples, HBoV positivity was detected in 9.2% of cases (64/692). Genotypes HBoV-1, HBoV-2, HBoV-3, and HBoV-4 were found in 42.5% (17/40), 22.5% (9/40), 32.5% (13/40), and 2.5% (1/40) of the specimens, respectively. Co-infections with HBoV and other enteric viruses occurred in 48.3% (31/64) of cases, with RVA being the most frequent (31.2%, 20/64). The study results underscore the importance of continuous monitoring and further research to better understand the seasonality, coinfection patterns, and genetic variability of HBoV. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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14 pages, 1529 KiB  
Article
Repurposing the Antidiabetic Drugs Glyburide, Gliquidone, and Glipizide in Combination with Benznidazole for Trypanosoma cruzi Infection
by Citlali Vázquez, Rusely Encalada, Isabel Jiménez-Galicia, Rogelio Gómez-Escobedo, Gildardo Rivera, Benjamín Nogueda-Torres and Emma Saavedra
Pharmaceuticals 2025, 18(1), 21; https://doi.org/10.3390/ph18010021 - 27 Dec 2024
Viewed by 1244
Abstract
Infection with the protozoan parasite Trypanosoma cruzi causes human Chagas disease. Benznidazole (BNZ) and nifurtimox are the current drugs for the treatment; however, they induce severe adverse side effects in patients; therefore, there is a need to improve the treatment effectiveness and efficiency [...] Read more.
Infection with the protozoan parasite Trypanosoma cruzi causes human Chagas disease. Benznidazole (BNZ) and nifurtimox are the current drugs for the treatment; however, they induce severe adverse side effects in patients; therefore, there is a need to improve the treatment effectiveness and efficiency of these drugs for its safer use. Background/Objective: Glyburide, glipizide, and gliquidone, hypoglycemic drugs for diabetes treatment, were previously predicted to bind to dihydrofolate reductase-thymidylate synthase from T. cruzi by in silico docking analysis; they also showed antiproliferative effects against T. cruzi epimastigotes, the stage of the insect vector. In the present study, the potential parasiticidal effect of these antidiabetic drugs was tested in monotherapy and bi-therapy with BNZ in human cells in vitro and in animals. Methods: Evaluation was performed in (a) a model of in vitro infection of T. cruzi trypomastigotes using human fibroblasts as host cells and (b) in mice infected with T. cruzi. Results: The antidiabetic drugs in monotherapy showed antiparasitic effects in preventing infection progression (trypomastigotes release), with an IC50 of 8.4–14.3 µM in comparison to that of BNZ (0.26 µM) in vitro. However, in bi-therapy, the presence of just 0.5 or 1 µM of the antidiabetics decreased the BNZ IC50 by 5–10 times to 0.03–0.05 µM. Remarkably, the antidiabetic drugs in monotherapy decreased the infection in mice by 40–60% in a similar extent to BNZ (80%). In addition, the combination of BNZ plus antidiabetics perturbed the antioxidant metabolites in epimastigotes. Conclusions: These results identified antidiabetics as potential drugs in combination therapy with BNZ to treat T. cruzi infection. Full article
(This article belongs to the Special Issue Drug Discovery and Development for Parasitic Diseases)
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16 pages, 2016 KiB  
Review
The Functions of Cytokines in the Cardiac Immunopathogenesis of Chagas Disease
by Mariana Citlalli de Alba-Alvarado, Margarita Cabrera-Bravo, Edgar Zenteno, Paz María Salazar-Schetino and Martha Irene Bucio-Torres
Pathogens 2024, 13(10), 870; https://doi.org/10.3390/pathogens13100870 - 3 Oct 2024
Cited by 4 | Viewed by 2365
Abstract
Chagas disease is a complex zoonosis. Clinically, it presents in two distinct phases, acute and chronic. The ability of patients to respond to Trypanosoma cruzi infection depends on the balance between inflammatory and anti-inflammatory responses, in which cytokines play a key regulatory role. [...] Read more.
Chagas disease is a complex zoonosis. Clinically, it presents in two distinct phases, acute and chronic. The ability of patients to respond to Trypanosoma cruzi infection depends on the balance between inflammatory and anti-inflammatory responses, in which cytokines play a key regulatory role. In this review, we discuss the role of cytokines in regulating the host response and as mediators of cardiac injury by inducing profibrotic alterations. The importance of characterizing cytokine profiles as biomarkers of the evolution of cardiac damage in T.-cruzi-infected individuals is also emphasized. Full article
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15 pages, 3785 KiB  
Article
Molecular Docking-Based Virtual Screening of FDA-Approved Drugs Using Trypanothione Reductase Identified New Trypanocidal Agents
by Rogelio Gómez-Escobedo, Domingo Méndez-Álvarez, Citlali Vázquez, Emma Saavedra, Karina Vázquez, Verónica Alcántara-Farfán, Joaquín Cordero-Martínez, Alonzo Gonzalez-Gonzalez, Gildardo Rivera and Benjamín Nogueda-Torres
Molecules 2024, 29(16), 3796; https://doi.org/10.3390/molecules29163796 - 10 Aug 2024
Cited by 2 | Viewed by 2341
Abstract
American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects approximately 6–7 million people worldwide. However, its pharmacological treatment causes several uncomfortable side effects, causing patients’ treatment abandonment. Therefore, there is a need for new and better treatments. In [...] Read more.
American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects approximately 6–7 million people worldwide. However, its pharmacological treatment causes several uncomfortable side effects, causing patients’ treatment abandonment. Therefore, there is a need for new and better treatments. In this work, the molecular docking of nine hundred twenty-four FDA-approved drugs on three different sites of trypanothione reductase of T. cruzi (TcTR) was carried out to find potential trypanocidal agents. Finally, biological evaluations in vitro and in vivo were conducted with the selected FDA-approved drugs. Digoxin, alendronate, flucytosine, and dihydroergotamine showed better trypanocidal activity than the reference drugs benznidazole and nifurtimox in the in vitro evaluation against the trypomastigotes form. Further, these FDA-approved drugs were able to reduce 20–50% parasitemia in a short time in an in vivo model, although with less efficiency than benznidazole. Therefore, the results suggest a combined therapy of repurposed and canonical drugs against T. cruzi infection. Full article
(This article belongs to the Special Issue The Design, Synthesis, and Biological Activity of New Drug Candidates)
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16 pages, 6097 KiB  
Article
Identification of Potential Trypanosoma cruzi Trans-Sialidase Inhibitors by Computational Drug Repositioning Approaches
by Miguel A. Uc-Chuc, Nohemi Cigarroa-Toledo, Karla Y. Acosta-Viana, José I. Chan-Pérez, Juan C. Pineda-Cortes and Hernán de J. Villanueva-Alonzo
Sci. Pharm. 2024, 92(3), 40; https://doi.org/10.3390/scipharm92030040 - 27 Jul 2024
Cited by 1 | Viewed by 1959
Abstract
Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi (T. cruzi), represents a worldwide public health issue. To date, there is no efficient treatment to combat this pathology, and the only drugs available are usually toxic to the patient. Through the [...] Read more.
Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi (T. cruzi), represents a worldwide public health issue. To date, there is no efficient treatment to combat this pathology, and the only drugs available are usually toxic to the patient. Through the enzyme trans-salidase, the parasite invades, infects, and multiplies intracellularly in the host cell. This protein has been considered an attractive target for developing or searching for compounds with potential trypanocidal activity. In this study, an in silico analysis was performed using a Food and Drug Administration-approved computational drug repositioning approach to identify compounds with anti-Chagas potential against two trans-sialidase proteins. Those compounds with potential inhibition were analyzed and selected through a molecular docking-based virtual screening. Forty-nine compounds were identified, of which forty-five are available on the market, and the rest were evaluated in silico. Our predicted results follow that these compounds are safe for human use and could be potential anti-trans-sialidase agents. Full article
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14 pages, 777 KiB  
Article
Chagas Disease in the Non-Endemic Area of Rome, Italy: Ten Years of Experience and a Brief Overview
by Maria Letizia Giancola, Andrea Angheben, Laura Scorzolini, Stefania Carrara, Ada Petrone, Antonella Vulcano, Raffaella Lionetti, Angela Corpolongo, Rosalia Marrone, Francesca Faraglia, Tommaso Ascoli Bartoli, Patrizia De Marco, Maria Virginia Tomassi, Carla Fontana and Emanuele Nicastri
Infect. Dis. Rep. 2024, 16(4), 650-663; https://doi.org/10.3390/idr16040050 - 24 Jul 2024
Cited by 1 | Viewed by 1978
Abstract
Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to [...] Read more.
Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to share our experience at the National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, in Rome, Italy, where to date, a total of 47 patients—mainly Bolivian women—diagnosed with CD have received treatment with benznidazole, with all but one presenting with chronic disease. Most of the patients were recruited through the first extensive screening program held in 2014 at our Institute. About a quarter of our patients showed adverse effects to benznidazole, including a case of severe drug-induced liver injury, but 83% completed a full course of treatment. In addition to the description of our cohort, the paper reports a brief overview of the disease compiled through a review of the existing literature on CD in non-endemic countries. The growing prevalence of CD in Western countries highlights the importance of screening at-risk populations and urges public concern and medical awareness about this neglected tropical disease. There are still many unanswered questions that need to be addressed to develop a personalized approach in treating patients. Full article
(This article belongs to the Section Neglected Tropical Diseases)
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Article
Pirfenidone Prevents Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy
by Tatiana Araújo Silva, Diane Thomas, Jair L. Siqueira-Neto and Claudia Magalhaes Calvet
Int. J. Mol. Sci. 2024, 25(13), 7302; https://doi.org/10.3390/ijms25137302 - 3 Jul 2024
Cited by 3 | Viewed by 2464
Abstract
Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-β [...] Read more.
Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-β (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast Green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect was independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the hearts of the patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Myocardial Disease)
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