Search Results (580)

The Triatoma rubrovaria subcomplex, comprising several triatomine species, plays a significant role in the transmission of Chagas disease in southern Brazil. Despite morphological distinctions among these species, their genetic differentiation remains poorly understood, particularly in sympatric regions. This study investigates the genetic diversity and phylogenetic relationships through DNA sequencing analysis of five sympatric species within the T. rubrovaria subcomplex (T. rubrovaria, T. carcavalloi, T. klugi, T. circummaculata, and T. pintodiasi), using a 542-bp fragment of the mitochondrial cytochrome b (mtCytb) gene. A total of 84 specimens were collected from six municipalities in Rio Grande do Sul, Brazil, and analyzed alongside laboratory-reared specimens and sequences from the GenBank. Bayesian phylogenetic reconstructions, haplotype networks, and population structure analyses revealed a lack of clear genetic differentiation among the five species, with overlapping intra- and interspecific divergences and shared haplotypes. These findings suggest either a single species exhibiting phenotypic plasticity or a group of incipient species with ongoing gene flow. This study highlights the need for a taxonomic revision and suggests that this group could serve as a valuable model for further genomic research to elucidate potential aspects of phenotypic plasticity and/or sympatric speciation in triatomines. Full article

The successful transmission of Trypanosoma cruzi, the causative agent of Chagas disease, depends on intricate interactions with its insect vector. In Mexico, Meccus pallidipennis is a relevant triatomine species involved in the parasite’s life cycle. In the gut of these insects, the parasite moves from the anterior midgut (AMG) to the posterior midgut (PMG), where it multiplies. Finally, T. cruzi differentiates into its infective form by metacyclogenesis in the proctodeum or rectum (RE). This study aimed to characterize and compare the protein and glycoprotein profiles of the anterior midgut (AMG) and rectum (RE) of M. pallidipennis, and to assess their potential association with T. cruzi metacyclogenesis, with special attention to sex-specific differences. Insects were infected with the T. cruzi isolate ITRI/MX/12/MOR (Morelos). Protein profiles were analyzed by polyacrylamide gel electrophoresis, while glycoproteins were detected using ConA, WGA, and PNA lectins. The metacyclogenesis index was calculated for male and female triatomines. A lower overlap of protein fractions was found in the RE compared to the AMG between sexes, suggesting functional sexual dimorphism. Infected females showed greater diversity in glycoprotein patterns in the RE, potentially related to higher blood intake and parasite burden. The metacyclogenesis index was significantly higher in females than in males. These findings highlight sex-dependent differences in gut protein and glycoprotein profiles in M. pallidipennis, which may influence the efficiency of T. cruzi development within the vector. Further proteomic studies are needed to identify the molecular components involved and clarify their roles in parasite differentiation and suggest new targets for disrupting parasite transmission within the vector. Full article

Via a One Health approach, this study concomitantly assessed the susceptibility of humans and dogs to Trypanosoma cruzi infections on three islands and in two mainland seashore areas of southern Brazil. Human serum samples were tested using an enzyme-linked immunosorbent assay (ELISA) to detect anti-T. cruzi antibodies, while dog serum samples were tested using indirect fluorescent antibodies in an immunofluorescence assay (IFA). Seropositive human and dog individuals were also tested using quantitative polymerase chain reaction (qPCR) in corresponding blood samples. Overall, 2/304 (0.6%) human and 1/292 dog samples tested seropositive for T. cruzi by ELISA and IFA, respectively, and these cases were also molecularly positive for T. cruzi by qPCR. Although a relatively low positivity rate was observed herein, these cases were likely autochthonous, and the individuals may have been infected as a consequence of isolated events of disturbance in the natural peridomicile areas nearby. Such a disturbance could come in the form of a fire or deforestation event, which can cause stress and parasitemia in wild reservoirs and, consequently, lead to positive triatomines. In conclusion, T. cruzi monitoring should always be conducted in suspicious areas to ensure a Chagas disease-free status over time. Further studies should also consider entomological and wildlife surveillance to fully capture the transmission and spread of T. cruzi on islands and in seashore mainland areas of Brazil and other endemic countries. Full article

Triatoma pallidipennis, the main vector of Chagas disease in central Mexico, hosts a diverse and complex gut bacterial community shaped by environmental and physiological factors. To gain insight into these microbes’ dynamics, we characterised the gut bacterial communities of wild and insectary insects under different feeding and Trypanosoma cruzi infection conditions, using 16S rRNA gene sequencing. We identified 91 bacterial genera across 8 phyla, with Proteobacteria dominating most samples. Wild insects showed greater bacterial diversity, led by Acinetobacter and Pseudomonas, while insectary insects exhibited lower diversity and were dominated by Arsenophonus. The origin of the insects, whether they were reared in the insectary (laboratory) or collected from wild populations, was the principal factor structuring the gut microbiota, followed by feeding and T. cruzi infection. A stable core microbiota of 12 bacterial genera was present across all conditions, suggesting key functional roles in host physiology. Co-occurrence and functional enrichment analyses revealed that feeding and infection induced condition-specific microbial interactions and metabolic pathways. Our findings highlight the ecological plasticity of the triatomine gut microbiota and its potential role in modulating vector competence, providing a foundation for future microbiota-based control strategies. Full article

Congenital Chagas disease (CCD) is caused when Trypanosoma cruzi crosses the placental barrier during pregnancy and reaches the fetus, which can lead to serious consequences in the developing fetus. Current treatment is carried out with nifurtimox or benznidazole, but their effectiveness is limited, and they cause side effects, requiring the search for new therapeutic strategies. In this sense, many studies have demonstrated the potential of different compounds of the Copaifera genus in the control of parasitic diseases. Here, we aimed to evaluate the effect of oleoresin (OR) and leaf hydroalcoholic extract (LHE) of Copaifera multijuga on Trypanosoma cruzi infection in human villous trophoblast cells (BeWo line) and human placenta explants. Treatment with both compounds reduced invasion, proliferation, and release of trypomastigotes. Furthermore, OR and LHE affected the trypomastigotes and amastigote morphology, compromising their ability to invade and proliferate in BeWo cells, respectively. Also, treatment with OR decreased ROS production in infected BeWo cells, while LHE induced an increase. In addition, both compounds induced pro-inflammatory and anti-inflammatory cytokine production. In human placental explants, both compounds also decreased T. cruzi infection, in addition to inducing the production of pro-inflammatory cytokines. Thus, both OR and LHE of C. multijuga control T. cruzi infection at the human maternal–fetal interface, highlighting the possible therapeutic potential of these compounds for the treatment of CCD. Full article

Background/Objectives: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a major neglected tropical disease, with over six million cases concentrated, primarily in Latin America. Despite decades of research, treatment continues to rely on two outdated drugs—benznidazole and nifurtimox—both of which exhibit limited efficacy and are associated with severe side effects. In this context, drug repurposing presents a promising strategy to accelerate the development of safer and more effective therapies. Nitroxoline, a hydroxyquinoline compound widely used in Europe to treat bacterial urinary tract infections, has recently garnered attention for its broad-spectrum antimicrobial and anticancer activities. This study evaluated the antitrypanosomal potential of nitroxoline against both epimastigote and intracellular amastigote forms of T. cruzi, demonstrating significantly greater efficacy than benznidazole. Methods: In addition to its antiparasitic activity, we investigated the mechanism of parasite death and found that nitroxoline induces hallmarks of programmed cell death, including chromatin condensation, mitochondrial membrane depolarization, ATP depletion, reactive oxygen species accumulation, and increased membrane permeability. These cellular events are critical for minimizing host tissue inflammation and suggest a safer therapeutic profile. Results: The nitroxoline was shown to induce greater activity than the reference treatment, benznidazole, in addition to triggering events related to apoptotic or silent cell death. Conclusions: Given its established clinical use and favorable safety data, nitroxoline emerges as a strong candidate for further investigation as a repurposed treatment for Chagas disease. Future work should focus on in vivo efficacy, pharmacokinetics, and drug delivery strategies to enhance systemic bioavailability. Full article

Chagas disease, caused by Trypanosoma cruzi, poses a significant public health challenge due to its widespread prevalence, limited therapeutic options, and adverse effects associated with available medications. In this study, we developed 13 novel pyrazole-imidazoline derivatives, inspired by a previously identified cysteine protease inhibitor, and evaluated their antiparasitic activity. Our in silico analyses predicted favorable physicochemical profiles and promising oral bioavailability for these derivatives. Upon phenotypic screening, we observed that these new derivatives exhibited low cytotoxicity (CC₅₀ > 100 µM) and marked efficacy against intracellular amastigotes. Derivative 1k showed high activity (IC₅₀ = 3.3 ± 0.2 µM), selectivity (SI = 73.9), and potency (pIC₅₀ = 5.4). In a 3D cardiac microtissue model, 1k significantly reduced parasite load, matching the efficacy of benznidazole (Bz) even at lower concentrations. Both 1k and Bz effectively prevented parasite recrudescence; however, neither resulted in parasite sterility under the experimental conditions employed. The combination of 1k–Bz yielded an additive interaction, highlighting its potential for in vivo combination therapy. While structural changes abolished cysteine protease inhibition, incorporating a CF₃ substituent at the para position and excluding the amino group enhanced antiparasitic activity. These findings reinforce the promise of the pyrazole-imidazoline scaffold and support further structural optimizations to develop innovative candidates for treating Chagas disease. Full article

The use of metal-based complexes is currently taking centre stage in the field of nanomedicine for the treatment and control of various ailments. Rhenium(I) tricarbonyl complexes have frequently been evaluated in vitro for their anticancer activities, and a few have advanced to in vivo and clinical trials, owing to the distinct application characteristics of these complexes. Their inception in drug development is key. This study explores a detailed chronological overview of the medical applications of Re(I) tricarbonyl complexes over the past six years (2019–2024), focusing on their applications and clinical tests in the control and management of various ailments. An in-depth examination of their activities in anticancer treatments, Chagas disease, antifungal infections, antimalarial, and microbial infections was conducted, comparing the complexes to various standard antibiotics, conventional antimalarial drugs, antifungals, and standard anticancer agents. Full article

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

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

Triatoma dimidiata is a widely distributed vector of Trypanosoma cruzi in Mexico and Central America, found across a range of habitats from sylvatic to domestic. Vector control has relied heavily on indoor residual spraying with pyrethroids; however, reinfestation and emerging resistance have limited its long-term effectiveness. In this study, we analyzed the genetic diversity and population structure of T. dimidiata from Veracruz, Oaxaca, and Yucatan using mitochondrial markers (cyt b and ND4) and screened for knockdown resistance (kdr)-type mutations in the voltage-gated sodium channel (VGSC) gene. High haplotype diversity and regional differentiation were observed, with most genetic variation occurring between populations. The ND4 marker provided greater resolution than cyt b, revealing ten haplotypes and supporting evidence of recent population expansion. Haplotype networks showed clear geographic segregation, particularly between populations east and west of the Isthmus of Tehuantepec. The L925I mutation, highly associated with pyrethroid resistance, was detected for the first time in Mexican populations of T. dimidiata, albeit at low frequencies. These findings highlight the importance of integrating population genetic data and resistance surveillance into regionally adapted vector control strategies for Chagas disease. Full article

Chagas disease (ChD) caused by Trypanosoma cruzi remains a major public health concern, affecting approximately 8 million people worldwide. However, the number of undiagnosed cases is likely much higher. Existing treatments rely on benznidazole and nifurtimox which, despite their efficacy during the acute phase of infection, are often associated with severe side effects that can be life-threatening. As a promising alternative, actinomycetes—which are renowned for producing pharmacologically and industrially relevant metabolites—have demonstrated potent antimicrobial properties; however, their antiparasitic potential remains largely unexplored. This study evaluated the anti-trypanocidal activities of extracellular metabolites produced by Streptomyces thermocarboxydus strain Chi-43 (ST-C43) and Streptomyces sp. strain Chi-104 (S-C104) against epimastigote, trypomastigote, and amastigote forms of T. cruzi. The strains were cultured in ISP2 broth, and their extracellular metabolites were assessed via antiparasitic diffusion assays in microplates. The 50% lethal concentration (LC₅₀) values ranged from 102 to 116 μg/mL against epimastigotes and trypomastigotes. The antiparasitic activity was confirmed through 3-(4,5-dimetiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based spectrophotometric assays and optical microscopy. Toxicity assays revealed that the extracellular metabolites were non-toxic to Artemia salina, non-cytotoxic to Huvecs, and non-hemolytic to human erythrocytes. Dose–response regression analysis showed statistically significant differences (p ≤ 0.05). LC-MS/MS analysis identified amphomycin and K-252c aglycone staurosporine as the active antiparasitic compounds. These findings highlight the potential of Streptomyces-derived extracellular metabolites as novel, selective, and safe anti-T. cruzi agents. Nevertheless, further studies in murine or preclinical models are needed to validate their efficacy and support future clinical applications for the treatment of ChD. Full article

Trypanosoma cruzi is a kinetoplastid parasite and etiological agent of Chagas disease. Given the significant morbidity and mortality rates of this parasitic disease, possible treatment alternatives need to be studied. 3-Bromopyruvate (3-BrPA) is a synthetic analog of pyruvate that was introduced in the early 21st century as an anticancer agent, affecting the proliferation and motility of certain microorganisms. Therefore, this work aims to evaluate the role of 3-BrPA in the energy metabolism, proliferation, and infectivity of T. cruzi, with a primary focus on the mitochondrial state, ATP production, and the key glycolytic pathway enzymes. It was observed that mitochondrial function in 3-BrPA cells was impaired compared to control cells. Accordingly, cells maintained in control conditions have a higher intracellular ATP content than cells maintained with 3-BrPA and higher ecto-phosphatase activity. However, the 3-BrPA reduced ecto-nuclease activity and was capable of hydrolyzing 5′-AMP, ADP, and ATP. When we evaluated two key glycolytic pathway enzymes, glucose kinase (GK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we observed that 3-BrPA induced higher GAPDH activity but did not alter GK activity. The compensatory energy mechanisms presented in T. cruzi may influence the process of cell metabolism and, consequently, the functional infectious process, suggesting the potential use of 3-BrPA in future clinical applications for Chagas disease. Full article

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), continues to pose significant public health challenges due to the toxicity, poor tolerability, and limited efficacy of current treatments. Targeted protein degradation (TPD) using proteolysis-targeting chimeras (PROTACs) represents a novel therapeutic avenue by leveraging the ubiquitin–proteasome system to selectively degrade essential parasite proteins. This review introduces the conceptual framework of “TrypPROTACs” as a prospective strategy for T. cruzi, integrating a comprehensive analysis of druggable targets across critical biological pathways, including ergosterol biosynthesis, redox metabolism, glycolysis, nucleotide synthesis, protein kinases, molecular chaperones such as heat shock protein 90 (Hsp90), and epigenetic regulators such as T. cruzi bromodomain factor 3 (TcBDF3). It is important to note that no TrypPROTAC compound has yet been synthesized or experimentally validated in T. cruzi; the approach discussed herein remains theoretical and forward-looking. Representative inhibitors for each target class are compiled, highlighting potency, selectivity, and structural features relevant to ligand design. We also examine the parasite’s ubiquitination machinery and compare it to the human system to identify putative E3 ubiquitin ligases. Key aspects of linker engineering and ternary complex stabilization are discussed, alongside potential validation techniques such as the cellular thermal shift assay (CETSA) and bioluminescence resonance energy transfer (NanoBRET). Collectively, these insights outline a roadmap for the rational design of TrypPROTACs and support the feasibility of expanding targeted protein degradation strategies to neglected tropical diseases. Full article

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques. Methods: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay. Results: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response. Conclusions: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria. Full article