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1.
PLoS Negl Trop Dis ; 14(12): e0008889, 2020 12.
Article in English | MEDLINE | ID: mdl-33351798

ABSTRACT

Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.


Subject(s)
Chagas Cardiomyopathy/metabolism , Chagas Cardiomyopathy/pathology , Gene Expression Regulation/physiology , MicroRNAs/metabolism , Chronic Disease , Genome, Human , Humans , MicroRNAs/genetics , Principal Component Analysis
2.
J Environ Manage ; 227: 386-394, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30212685

ABSTRACT

Rehabilitation of tailing dams poses important challenges because sterile materials and poor or even toxic soils hinder plant development and the regeneration of the pre-mining-activity biota. In this study, we analyzed the effectiveness of rehabilitating a 14-year-old manganese tailing dam by comparing three different regeneration treatments (topsoil application, seedling plantation and spontaneous regeneration) with undisturbed reference sites. We used soil chemical composition, taxonomic, functional and phylogenetic diversity and the above-ground tree biomass as indicators of rehabilitation success. In terms of soil chemical composition, we showed that the seedling and natural regeneration treatments were similar to one another but different from the reference sites. Topsoil application presented an intermediate chemical composition between the reference site and the other two treatments. Moreover, the species richness, Shannon diversity index and phylogenetic diversity indicated faster rehabilitation of ecosystem biodiversity with the topsoil treatment, although levels from reference are not yet achieved. We also observed higher basal area and biomass production in the topsoil treatment. However, these patterns were not observed for functional diversity, for which no differences among treatments were observed. We concluded that topsoil application provided the best results; however, we must emphasize that even this approach was not sufficient to rehabilitate the system to the similar level of biodiversity found in the surrounding ecosystem up to the present.


Subject(s)
Biodiversity , Manganese , Phylogeny , Plants , Ecosystem , Soil
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