156 research outputs found
Understanding global changes of the liver proteome during murine schistosomiasis using a label-free shotgun approach.
Schistosomiasis is an endemic disease affecting over 207million people worldwide caused by helminth parasites
of the genus Schistosoma. In Brazil the disease is responsible for the loss of up to 800 lives annually, resulting from
the desabilitating effects of this chronic condition. In this study, we infected Balb/c mice with Schistosoma
mansoni and analysed global changes in the proteomic profile of soluble liver proteins. Our shotgun analyses revealed
predominance of up-regulation of proteins at 5weeks of infection, coincidingwith the onset of egg laying,
and a remarkable down-regulation of liver constituents at 7 weeks, when severe tissue damage is installed. Representatives
of glycolytic enzymes and stress response (in particular at the endoplasmic reticulum)were among
the most differentially expressed molecules found in the infected liver. Collectively, our data contribute over 70
molecules not previously reported to be found at altered levels in murine schistosomiasis to further exploration
of their potential as biomarkers of the disease.Moreover, understanding their intricate interaction using bioinformatics
approach can potentially bring clarity to unknownmechanisms linked to the establishment of this condition
in the vertebrate host.
Significance: To our knowledge, this study refers to the first shotgun proteomic analysis to provide an inventory of
the global changes in the liver soluble proteome caused by Schistosomamansoni in the Balb/cmodel. It also innovates
by yielding data on quantification of the identified molecules as a manner to clarify and give insights into
the underlying mechanisms for establishment of Schistosomiasis, a neglected tropical disease with historical
prevalence in Brazil
Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.This work was supported by ‘‘Ministerio de Ciencia e Innovación’’ (SAF2010-17833); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538 and PI12/00289); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ‘‘Fundación Ramón Areces’Peer Reviewe
Crescimento de mudas de cipó-cravo (Tynanthus fasciculatus Miers), uma liana com potencial medicinal
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