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Purpose: Meniscal injuries are common in knee surgery and often require preservation techniques to prevent secondary osteoarthritis. Despite advancements in repair techniques, some patients undergo partial meniscectomy, which can lead to postmeniscectomy syndrome. To address these challenges, meniscal substitution techniques like scaffolds have been developed. However, a comprehensive synthesis of the existing evidence through an umbrella review is lacking. Methods: A comprehensive search was conducted in the MEDLINE, Embase and Scopus databases to identify relevant systematic reviews and meta-analyses. Studies were screened based on predefined inclusion and exclusion criteria. The quality of included studies was assessed using the AMSTAR-2 tool. Results: A total of 17 studies met the inclusion criteria and were included in the review. Most studies focused on the use of collagen-based scaffolds, with fewer studies evaluating synthetic scaffolds. The majority of studies (52.9%) were rated as having 'Critically Low' overall confidence, with only one study (5.9%) rated as 'High' confidence and most studies exhibiting methodological limitations, such as small sample sizes and lack of long-term follow-up. Despite these limitations, the majority of studies reported positive short-term outcomes, including pain relief and functional improvement, following scaffold implantation. However, some studies noted a relatively high failure rate. Radiographically, outcomes also varied, with some studies reporting morphological deterioration of the implant seen on MRI, while others noted possible chondroprotective effects. Conclusions: Meniscal scaffold-based approaches show promise in the management of meniscal deficiency; however, the current evidence is limited by methodological shortcomings. One notable gap in the literature is the lack of clear guidelines for patient selection and surgical technique. Future research should focus on conducting well-designed randomized controlled trials with long-term follow-up to further elucidate the benefits and indications of these techniques in clinical practice. Additionally, efforts should be made to develop consensus guidelines to standardize the use of meniscal scaffolds and improve patient outcomes. Despite limited availability, synthesizing the literature on meniscal scaffold-based approaches is crucial for understanding research, guiding clinical decisions and informing future directions. Level of Evidence: Level IV.
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The placenta plays a critical role in host-pathogen interactions. Thus, ex vivo infection of mammalian placental explants is an excellent and simple method to study the mechanisms of cellular and tissue invasion by different pathogens in different mammalian species. These explants can be maintained in culture for several days, preserving the tissue architecture and resembling in-utero conditions under more physiological conditions than their isolated counterparts in isolated cell culture models. In addition, placental explants not only allow us to study how the placenta responds and defends itself against various infections but also provide a versatile platform for advancing our understanding of placental biology and the immune response. Furthermore, they serve as powerful tools for drug discovery, facilitating the screening of potential therapeutics for placental infections and for the identification of diagnostic markers. This review highlights the utility of mammalian placental explants in studying the host-pathogen interaction of two relevant protozoan parasites, Trypanosoma cruzi, the causative agent of Chagas disease, and Toxoplasma gondii, the etiological agent of Toxoplasmosis. Here, we discuss the different methodologies and technical aspects of the model, as well as the effect of both parasites on placental responses in human, canine, and ovine explants.
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Chagas disease is caused by the single-flagellated protozoan Trypanosoma cruzi, which affects several million people worldwide. Understanding the signal transduction pathways involved in this parasite's growth, adaptation, and differentiation is crucial. Understanding the basic mechanisms of signal transduction in T. cruzi could help to develop new drugs to treat the disease caused by these protozoa. In the present work, we have demonstrated that Fetal Calf Serum (FCS) can quickly increase the levels of both phosphorylated and unphosphorylated forms of T. cruzi DNA polymerase beta (TcPolß) in tissue-cultured trypomastigotes. The in vitro phosphorylation sites on TcPolß by protein kinases TcCK1, TcCK2, TcAUK1, and TcPKC1 have been identified by Mass Spectrometry (MS) analysis and with antibodies against phosphor Ser-Thr-Tyr. MS analysis indicated that these protein kinases can phosphorylate Ser and Thr residues on several sites on TcPolß. Unexpectedly, it was found that TcCK1 and TcPKC1 can phosphorylate a different Tyr residue on TcPolß. By using a specific anti-phosphor Tyr monoclonal antibody, it was determined that TcCK1 can be in vitro autophosphorylated on Tyr residues. In vitro and in vivo studies showed that phorbol 12-myristate 13-acetate (PMA) can activate the PKC to stimulate the TcPolß phosphorylation and enzymatic activity in T. cruzi epimastigotes.
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ABSTRACT Purpose: to characterize the practices of speech-language-hearing pathologists in Chile, regarding speech perception assessment in children and adolescents. Methods: an exploratory cross-sectional study carried out using a self-administered online survey to investigate knowledge and quantify trends in the practice of speech perception assessment, based on six focus groups with speech-language-hearing pathologists. The instrument was disseminated through the researchers' social media and contact networks. Descriptive statistical analysis was performed. Results: a total of 121 people responded to the survey, all of them being speech-language-hearing pathologists. These professionals, in Chile, highly value speech perception in child development, however, a large percentage of them do not assess it. Those who carry it out, reported a wide range of assessment practices. Conclusion: the results highlight the need for standardizing certain speech-language-hearing methods and the importance of understanding the assessment strategies in use to point out opportunities to improve both the assessment and subsequent therapeutic processes.
RESUMEN Objetivo: caracterizar las prácticas de los profesionales de la Fonoaudiología en Chile en torno a la evaluación de la percepción del habla en niños, niñas y adolescentes. Métodos: se realizó un estudio exploratorio de diseño transversal mediante una encuesta online autoadministrada diseñada para indagar en los saberes y cuantificar tendencias en la práctica de la evaluación de la percepción del habla. La encuesta fue confeccionada en base a seis grupos focales realizados con profesionales fonoaudiólogos. La difusión del instrumento se realizó a través de redes sociales y redes de contacto de los investigadores. El análisis estadístico realizado fue de carácter descriptivo. Resultados: un total de 121 personas respondieron la encuesta, todos profesionales de la Fonoaudiología. Los profesionales de la Fonoaudiología en Chile otorgan un alto valor a la percepción del habla en el desarrollo infantil, no obstante, un gran porcentaje no la evalúa. Aquellos profesionales que lo realizan, revelan una amplia diversidad en las prácticas evaluativas. Conclusión: los resultados permiten visibilizar la necesidad de estandarizar ciertos métodos fonoaudiológicos y resaltar la importancia de comprender las estrategias evaluativas en uso para señalar oportunidades de mejora tanto en la evaluación como en los posteriores procesos terapéuticos.
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INTRODUCTION: Upon infection, Trypanosoma cruzi, a protozoan parasite, crosses the placental barrier and causes congenital Chagas disease. Ex vivo infection of human placental explants (HPEs) with the parasite induces apoptotic cell death. This cellular process involves changes in gene expression, which are partially regulated by miRNAs. In this study, we investigated the role of miR-512-3p, a highly expressed miRNA in the placenta, in parasite-induced apoptosis. METHODS: HPE cells were transfected with antagomirs or mimics of miR-512-3p and subsequently challenged with the parasite. The expression levels of miR-512-3p, caspase 3, caspase 8, and Livin were measured using RT-qPCR, and apoptotic cell death was analyzed based on caspase activity and DNA fragmentation assays. RESULTS: Targeted inhibition of miR-512-3p effectively prevented parasite-induced expression and enzymatic activity of caspase 3 and caspase 8. However, it did not completely prevent DNA fragmentation, indicating the involvement of other factors in this process. Furthermore, the findings suggest that Livin may be regulated by miR-512-3p. DISCUSSION: Our findings suggest that miR-512-3p modulates parasite-induced apoptosis in the trophoblast. By understanding the mechanisms involved in this process, we can gain insights into the pathogenesis of congenital Chagas disease and develop targeted therapeutic strategies.
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Enfermedad de Chagas , MicroARNs , Trypanosoma cruzi , Humanos , Embarazo , Femenino , Placenta/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Caspasa 3/metabolismo , Caspasa 8 , Enfermedad de Chagas/genética , Apoptosis/genéticaRESUMEN
Fission yeast ribosomal protein genes (RPGs) contain a HomolD box as a core promoter element required for transcription. Some of the RPGs also contain a consensus sequence named HomolE, located upstream of the HomolD box. The HomolE box acts as an upstream activating sequence (UAS), and it is able to activate transcription in RPG promoters containing a HomolD box. In this work, we identified a HomolE-binding protein (HEBP) as a polypeptide of 100 kDa, which was able to bind to the HomolE box in a Southwestern blot assay. The features of this polypeptide were similar to the product of the fhl1 gene of fission yeast. The Fhl1 protein is the homolog of the FHL1 protein of budding yeast and possesses fork-head-associated (FHA) and fork-head (FH) domains. The product of the fhl1 gene was expressed and purified from bacteria, and it was demonstrated that is able to bind the HomolE box in an electrophoretic mobility assay (EMSA), as well as being able to activate in vitro transcription from an RPG gene promoter containing HomolE boxes upstream of the HomolD box. These results indicate that the product of the fhl1 gene of fission yeast can bind to the HomolE box, and it activates the transcription of RPGs.
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Schizosaccharomyces , Proteínas Portadoras/metabolismo , Regiones Promotoras Genéticas , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Transcripción GenéticaRESUMEN
DNA polymerase ß plays a fundamental role in the life cycle of Trypanosoma cruzi since it participates in the kinetoplast DNA repair and replication. This enzyme can be found in two forms in cell extracts of T. cruzi epimastigotes form. The H form is a phosphorylated form of DNA polymerase ß, while the L form is not phosphorylated. The protein kinases which are able to in vivo phosphorylate DNA polymerase ß have not been identified yet. In this work, we purified the H form of this DNA polymerase and identified the phosphorylation sites. DNA polymerase ß is in vivo phosphorylated at several amino acid residues including Tyr35, Thr123, Thr137 and Ser286. Thr123 is phosphorylated by casein kinase 2 and Thr137 and Ser286 are phosphorylated by protein kinase C-like enzymes. Protein kinase C encoding genes were identified in T. cruzi, and those genes were cloned, expressed in bacteria and the recombinant protein was purified. It was found that T. cruzi possesses three different protein kinase C-like enzymes named TcPKC1, TcPKC2, and TcPKC3. Both TcPKC1 and TcPKC2 were able to in vitro phosphorylate recombinant DNA polymerase ß, and in addition, TcPKC1 gets auto phosphorylated. Those proteins contain several regulatory domains at the N-terminus, which are predicted to bind phosphoinositols, and TcPKC1 contains a lipocalin domain at the C-terminus that might be able to bind free fatty acids. Tyr35 is phosphorylated by an unidentified protein kinase and considering that the T. cruzi genome does not contain Tyr kinase encoding genes, it is probable that Tyr35 could be phosphorylated by a dual protein kinase. Wee1 is a eukaryotic dual protein kinase involved in cell cycle regulation. We identified a Wee1 homolog in T. cruzi and the recombinant kinase was assayed using DNA polymerase ß as a substrate. T. cruzi Wee1 was able to in vitro phosphorylate recombinant DNA polymerase ß, although we were not able to demonstrate specific phosphorylation on Tyr35. Those results indicate that there exists a cell signaling pathway involving PKC-like kinases in T. cruzi.
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Enfermedad de Chagas , ADN Polimerasa beta , Trypanosoma cruzi , Humanos , ADN Polimerasa beta/genética , ADN Polimerasa beta/metabolismo , Quinasa de la Caseína II/metabolismo , Proteína Quinasa C/metabolismoRESUMEN
Trypanosoma cruzi and Toxoplasma gondii are two zoonotic parasites that constitute significant human and animal health threats, causing a significant economic burden worldwide. Both parasites can be transmitted congenitally, but transmission rates for T. gondii are high, contrary to what has been observed for T. cruzi. The probability of congenital transmission depends on complex interactions between the pathogen and the host, including the modulation of host cell gene expression by miRNAs. During ex vivo infection of canine and ovine placental explants, we evaluated the expression of 3 miRNAs (miR-30e-3p, miR-3074-5p, and miR-127-3p) previously associated with parasitic and placental diseases and modulated by both parasites. In addition, we identified the possible target genes of the miRNAs by using computational prediction tools and performed GO and KEGG enrichment analyses to identify the biological functions and associated pathologies. The three miRNAs are differentially expressed in the canine and ovine placenta in response to T. cruzi and T. gondii. We conclude that the observed differential expression and associated functions might explain, at least partially, the differences in transmission rates and susceptibility to parasite infection in different species.
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Enfermedad de Chagas , MicroARNs , Toxoplasma , Trypanosoma cruzi , Animales , Enfermedad de Chagas/veterinaria , Perros , Femenino , Humanos , MicroARNs/genética , Placenta/parasitología , Embarazo , Ovinos , Toxoplasma/genética , Trypanosoma cruzi/genéticaRESUMEN
MicroRNAs (miRNAs) are a group of small non-coding RNAs present in a wide diversity of organisms. MiRNAs regulate gene expression at a post-transcriptional level through their interaction with the 3' untranslated regions of target mRNAs, inducing translational inhibition or mRNA destabilization and degradation. Thus, miRNAs regulate key biological processes, such as cell death, signal transduction, development, cellular proliferation and differentiation. The dysregulation of miRNAs biogenesis and function is related to the pathogenesis of diseases, including parasite infection. Moreover, during host-parasite interactions, parasites and host miRNAs determine the probability of infection and progression of the disease. The present review is focused on the possible role of miRNAs in the pathogenesis of diseases of clinical interest caused by parasitic protists. In addition, the potential role of miRNAs as targets for the design of drugs and diagnostic and prognostic markers of parasitic diseases is also discussed.
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MicroARNs , Parásitos , Regiones no Traducidas 3' , Animales , Regulación de la Expresión Génica , Interacciones Huésped-Parásitos/genética , MicroARNs/metabolismo , Parásitos/genética , Parásitos/metabolismoRESUMEN
Chagas disease, or American trypanosomiasis, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi) [...].
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Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.
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microRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally through their interaction with the 3' untranslated regions (3' UTR) of target mRNAs, affecting their stability and/or translation. Therefore, miRNAs regulate biological processes such as signal transduction, cell death, autophagy, metabolism, development, cellular proliferation, and differentiation. Dysregulated expression of microRNAs is associated with infectious diseases, where miRNAs modulate important aspects of the parasite-host interaction. Helminths are parasitic worms that cause various neglected tropical diseases affecting millions worldwide. These parasites have sophisticated mechanisms that give them a surprising immunomodulatory capacity favoring parasite persistence and establishment of infection. In this review, we analyze miRNAs in infections caused by helminths, emphasizing their role in immune regulation and its implication in diagnosis, prognosis, and the development of therapeutic strategies.
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Introduction: Chronic Chagasic cardiomyopathy (CCC), caused by the protozoan Trypanosoma cruzi, is the most severe manifestation of Chagas disease.CCC is characterized by cardiac inflammation and fibrosis caused by a persistent inflammatory response. Following infection, macrophages secrete inflammatory mediators such as IL-1ß, IL-6, and TNF-α to control parasitemia. Although this response contains parasite infection, it causes damage to the heart tissue. Thus, the use of immunomodulators is a rational alternative to CCC. Rho-associated kinase (ROCK) 1 and 2 are RhoA-activated serine/threonine kinases that regulate the actomyosin cytoskeleton. Both ROCKs have been implicated in the polarization of macrophages towards an M1 (pro-inflammatory) phenotype. Statins are FDA-approved lipid-lowering drugs that reduce RhoA signaling by inhibiting geranylgeranyl pyrophosphate (GGPP) synthesis. This work aims to identify the effect of statins on U937 macrophage polarization and cardiac tissue inflammation and its relationship with ROCK activity during T. cruzi infection. Methods: PMA-induced, wild-type, GFP-, CA-ROCK1- and CA-ROCK2-expressing U937 macrophages were incubated with atorvastatin, or the inhibitors Y-27632, JSH-23, TAK-242, or C3 exoenzyme incubated with or without T. cruzi trypomastigotes for 30 min to evaluate the activity of ROCK and the M1 and M2 cytokine expression and secretion profiling. Also, ROCK activity was determined in T. cruzi-infected, BALB/c mice hearts. Results: In this study, we demonstrate for the first time in macrophages that incubation with T. cruzi leads to ROCK activation via the TLR4 pathway, which triggers NF-κB activation. Inhibition of ROCKs by Y-27632 prevents NF-κB activation and the expression and secretion of M1 markers, as does treatment with atorvastatin. Furthermore, we show that the effect of atorvastatin on the NF-kB pathway and cytokine secretion is mediated by ROCK. Finally, statin treatment decreased ROCK activation and expression, and the pro-inflammatory cytokine production, promoting anti-inflammatory cytokine expression in chronic chagasic mice hearts. Conclusion: These results suggest that the statin modulation of the inflammatory response due to ROCK inhibition is a potential pharmacological strategy to prevent cardiac inflammation in CCC.
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Cardiomiopatías , Enfermedad de Chagas , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Trypanosoma cruzi , Humanos , Animales , Ratones , Trypanosoma cruzi/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Quinasas Asociadas a rho/metabolismo , FN-kappa B/metabolismo , Atorvastatina/farmacología , Células U937 , Macrófagos/metabolismo , Enfermedad de Chagas/genética , Citocinas/metabolismo , Cardiomiopatías/metabolismo , Inflamación/metabolismoRESUMEN
BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapeutic agent to regulate the pro-inflammatory state during the early chronic phase of Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 µg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 µg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the early chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue. CONCLUSIONS/SIGNIFICANCE: AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during early chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite.
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Cardiomiopatía Chagásica/tratamiento farmacológico , Ácidos Docosahexaenoicos/administración & dosificación , Animales , Cardiomiopatía Chagásica/genética , Cardiomiopatía Chagásica/inmunología , Cardiomiopatía Chagásica/parasitología , Enfermedad Crónica/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Corazón/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/inmunología , Nitroimidazoles/administración & dosificación , Carga de Parásitos , Receptores de Formil Péptido/genética , Receptores de Formil Péptido/inmunología , Trypanosoma cruzi/fisiologíaRESUMEN
Apicomplexans are a group of pathogenic protists that cause various diseases in humans and animals that cause economic losses worldwide. These unicellular eukaryotes are characterized by having a complex life cycle and the ability to evade the immune system of their host organism. Infections caused by some of these parasites affect millions of pregnant women worldwide, leading to various adverse maternal and fetal/placental effects. Unfortunately, the exact pathogenesis of congenital apicomplexan diseases is far from being understood, including the mechanisms of how they cross the placental barrier. In this review, we highlight important aspects of the diseases caused by species of Plasmodium, Babesia, Toxoplasma, and Neospora, their infection during pregnancy, emphasizing the possible role played by the placenta in the host-pathogen interaction.
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Chagas disease and toxoplasmosis, caused by Trypanosoma cruzi and Toxoplasma gondii, respectively, are important zoonotic diseases affecting humans, companion animals, and livestock, responsible for major health and economic burden. Both parasites can be transmitted vertically in different mammalian species through the placenta. Of note, the transmission rate of T. cruzi is low in dogs, whereas that of T. gondii is high in sheep. The probability of congenital infection depends on complex parasite-host interactions; parasite factors, maternal and fetal immune responses and placental responses all have a role in infection establishment. Since the innate immune response is regulated, at least partially, by NF-κB signaling pathways, our main objective was to determine the effect of ex vivo infection of canine (CPE) and ovine (OPE) placental explants with both parasites, on the activation of canonical and non-canonical NF-κB pathways and its relation to infection. Here, we show that T. cruzi activates both the NF-κB canonical and non-canonical pathways in CPE and OPE, unlike T. gondii, that activates only the canonical pathway in CPE and has no effect on the non-canonical pathway in both explants. Moreover, the inhibition of either or both NF-κB pathways increases the DNA load of T. cruzi in both explants, modulates, on the other hand, T. gondii infection in a differential fashion. Overall, we conclude that the differential modulation of the NF-κB pathways by both pathogens in placental explants might explain, at least partially, the differences in transmission rates of T. cruzi and T. gondii in different mammalian species.
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Perros/metabolismo , Placenta/parasitología , Ovinos/metabolismo , Transducción de Señal/inmunología , Toxoplasma/fisiología , Trypanosoma cruzi/fisiología , Animales , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inmunidad Innata , Isoquinolinas/farmacología , FN-kappa B/metabolismo , Nitrilos/farmacología , Placenta/inmunología , Placenta/metabolismo , Embarazo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sulfonas/farmacología , Técnicas de Cultivo de Tejidos , Toxoplasma/inmunología , Trypanosoma cruzi/inmunologíaRESUMEN
Trypanosoma cruzi and Toxoplasma gondii are two parasites than can be transmitted from mother to child through the placenta. However, congenital transmission rates are low for T. cruzi and high for T. gondii. Infection success or failure depends on complex parasite-host interactions in which parasites can alter host gene expression by modulating non-coding RNAs such as miRNAs. As of yet, there are no reports on altered miRNA expression in placental tissue in response to either parasite. Therefore, we infected human placental explants ex vivo by cultivation with either T. cruzi or T. gondii for 2 h. We then analyzed the miRNA expression profiles of both types of infected tissue by miRNA sequencing and quantitative PCR, sequence-based miRNA target prediction, pathway functional enrichment, and upstream regulator analysis of differentially expressed genes targeted by differentially expressed miRNAs. Both parasites induced specific miRNA profiles. GO analysis revealed that the in silico predicted targets of the differentially expressed miRNAs regulated different cellular processes involved in development and immunity, and most of the identified KEGG pathways were related to chronic diseases and infection. Considering that the differentially expressed miRNAs identified here modulated crucial host cellular targets that participate in determining the success of infection, these miRNAs might explain the differing congenital transmission rates between the two parasites. Molecules of the different pathways that are regulated by miRNAs and modulated during infection, as well as the miRNAs themselves, may be potential targets for the therapeutic control of either congenital Chagas disease or toxoplasmosis.
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Enfermedad de Chagas , Regulación de la Expresión Génica/inmunología , MicroARNs/inmunología , Placenta , Toxoplasma/inmunología , Toxoplasmosis , Trypanosoma cruzi/inmunología , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/patología , Femenino , Humanos , Placenta/inmunología , Placenta/parasitología , Placenta/patología , Embarazo , Toxoplasmosis/inmunología , Toxoplasmosis/patologíaRESUMEN
El artículo analiza, desde los planteamientos del enfoque comunitario, una experiencia fonoaudiológica para la promoción de derechos de niños y niñas, efectuada en una organización social, con participación de un grupo de estudiantes de la carrera de Fonoaudiología de la Universidad de Chile en el año 2013. En los abordajes comunitarios, la comunidad construye conocimientos y realiza acciones para lograr el fortalecimiento de sus relaciones, bienestar social, justicia, autonomía y emancipación. El análisis de la experiencia se realiza a partir de una selección de las bitácoras de campo del equipo de estudiantes participantes, en base a los principios y dimensiones del paradigma de la construcción y transformación crítica de Maritza Montero (2004). Los resultados se dividen en tres momentos (inicio, transición y reconfiguración del trabajo), los cuales dan cuenta del grado de complejidad del proceso y los alcances obtenidos en base a las dimensiones: ontológica, epistemológica, metodológica, ética y política del enfoque comunitario. La discusión enfatiza la importancia de la reflexión crítica sobre los fundamentos y las prácticas de la Fonoaudiología en el abordaje de la comunicación y el desarrollo humano, para aportar a la justicia social desde el enfoque comunitario.
This paper analyzes, from a community-based approach, a speech, language and hearing sciences therapy experience for the promotion of children's rights, carried out in a social organization, with the participation of a group of speech, language and hearing sciences therapy undergraduate students at the Universidad de Chile in 2013. In community approaches, all community members build knowledge and take actions to build stronger social relationships and welfare, justice, autonomy and emancipation. The analysis of this experience was conducted by selecting sections from the fieldwork diaries of the team of participating students, based on the principles and dimensions of the paradigm of construction and critical transformation of Maritza Montero (2004). The results were divided into three moments (beginning, transition and reset of the work), which account for the level of complexity of the process and the goals achieved basedon the ontological, epistemological, methodological, ethical and political dimensions of the community-based approach. The discussion emphasizes the importance of critical reflection on the foundations and practices of speech, language and hearing sciences therapy in the approach to communication and human development, to contribute to social justice from a community perspective.
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Humanos , Masculino , Femenino , Niño , Justicia Social , Comunicación , Participación de la Comunidad , FonoaudiologíaRESUMEN
INTRODUCTION: Chagas disease, caused by the protozoan parasiteTrypanosoma cruzi, has no effective treatment available. On the other hand, microalgae are aquatic organisms that constitute an interesting reservoir of biologically active metabolites. Moreover, some species of green and red algae present anti-protozoan activity. Our aim was to study the antiparasitic effects of aqueous, methanolic and ethanolic extracts from different microalgae. METHODS AND RESULTS: Our results show that the methanolic extracts of S. obliquus and T. suecica as well as the ethanolic extracts of C. reinhardtii and T. suecica present trypanocidal activity on the infective extracellular trypomastigotes and intracellular amastigotes. In addition, the ethanolic extract of C. reinhardtii potentiates the activity of the conventional antichagasic drug nifurtimox. In order to identify some potential compounds with trypanocidal activity, we performed a phytochemical screening analyzing the presence of phenolic compounds, pigments and terpenoids. CONCLUSION: The different microalgae extracts, particularly the ethanolic extract ofC. reinhardtii, are promising potential candidates for the development of future natural antichagasic drugs.
Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Microalgas/química , Tripanocidas/aislamiento & purificación , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Enfermedad de Chagas/parasitología , Chlorocebus aethiops , Etanol/química , Metanol/química , Células VeroRESUMEN
Chagas disease, caused by the protozoan Trypanosoma cruzi, endemic in Latin America but distributed worldwide because of migration. Without appropriate treatment, the disease progresses from an acute asymptomatic phase to a chronic, progressive inflammatory cardiomyopathy causing heart failure and death. Despite specific trypanocidal therapy, heart damage progression cannot be stopped or reversed. Statins, as part of their pleiotropic actions, can modulate chagasic myocarditis by inducing the production of 15-epi-lipoxin A4 (15-epi-LXA4), a proresolution lipid mediator in inflammation. Furthermore, several reports suggest that simvastatin activates the Notch pathway after stroke in cerebral endothelial cells, enhancing blood flow by promoting angiogenesis. Thus, statins are an attractive therapeutic strategy for modulating the Notch pathway to reverse the chronic heart damage induced by T. cruzi BALB/c mice chronically infected with T. cruzi were treated with 1 mg/kg/day simvastatin or 25 µg/kg/day 15-epi-LXA4 for 20 days. During the treatment period, cardiac function was evaluated by echocardiography. At 80 days postinfection, the heart tissues were assessed for Notch 1 activity. T. cruzi infection activated the Notch 1 pathway, and simvastatin (but not 15-epi-lipoxin A4) produced a further increase in that activity, correlating with improvement in the ejection fraction and histopathologic findings typical of T. cruzi infection, including improvements in inflammation and fibrosis. Moreover, simvastatin increased the number of isolectin B4-positive cells, suggesting active angiogenesis in the chronically infected hearts without alteration of the parasitic load. Simvastatin, probably acting through the Notch 1 pathway, decreases inflammation, improving cardiac function in mice chronically infected with T. cruzi.