Differential expression profiles of miRNAs and their putative targets in Schistosoma mansoni during its life cycle

BACKGROUND Schistosomiasis is a disease caused by Schistosoma. Due to its complex life cycle, evolutionary position and sexual dimorphism, schistosomes have several mechanisms of gene regulation. MicroRNAs (miRNAs) are short endogenous RNAs that regulate gene expression at the post-transcriptional level by targeting mRNA transcripts. OBJECTIVES Here, we tested 12 miRNAs and identified their putative targets using a computational approach. METHODS We performed the expression profiles of a set of miRNAs and their putative targets during the parasite's life cycle by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). FINDINGS Our results showed differential expression patterns of the mature miRNAs sma-miR-250; sma-miR-92a; sma-miR-new_4-3p; sma-miR-new_4-5p; sma-miR-new_5-5p; sma-miR-new_12-5p; sma-miR-new_13-3p and sma-miR-new_13-5p. Interestingly, many of the putative target genes are linked to oxidative phosphorylation and are up-regulated in adult-worms, which led us to suggest that miRNAs might play important roles in the post-transcriptional regulation of genes related to energetic metabolism inversion during parasite development. It is noteworthy that the expression of sma-miR-new_13-3p exhibited a negative correlation on SmNADH:ubiquinone oxidoreductase complex I. MAIN CONCLUSIONS Our analysis revealed putative miRNA genes related to important biological processes, such as transforming growth factor beta (TGF-β) signaling, proteasome regulation, glucose and lipid metabolism, immune system evasion and transcriptional regulation.

High-sugar diet leads to obesity and metabolic diseases in ad libitum -fed rats irrespective of caloric intake

ABSTRACT Objective Provide a comprehensive view of the events surrounding the sugar consumption, under conditions of energy equivalence; through the analysis of behavioral aspects of intake, and of biochemical, metabolic and physiological parameters, as well as the effect of this nutrient on the plasticity of adipose tissue. Materials and methods Newly weaned male Wistar rats were classified in two groups and subjected to the following normocaloric diets: standard chow diet or to high-sugar diet (HSD) ad libitum for 18 weeks. Results The animals submitted to the HSD were associated with a lower caloric intake during the 18 weeks of experimentation. However, the HSD induced a significant increase in body weight, white adipose tissue weight, adiposity index, Lee index, and the levels of triglycerides and very low-density lipoprotein in the serum. In addition, it induced glucose intolerance, insulin resistance and compensatory increase of insulin secretion by pancreatic β-cells. Also increased heart rate and induced hyperplasia, and hypertrophy of retroperitoneal visceral adipose tissue. In the liver, the HSD was associated with increased hepatic lipid content (i.e., triglycerides and cholesterol) and hepatomegaly. Conclusion The post-weaning consumption of HSD induces an adaptive response in metabolism; however, such an event is not enough to reverse the homeostatic imbalance triggered by the chronic consumption of this macronutrient, leading to the development of metabolic syndrome, irrespective of caloric intake. These findings corroborate recent evidence indicating that sugar is a direct contributor to metabolic diseases independent of a positive energy balance. Arch Endocrinol Metab. 2020;64(1):71-81

Conservation and developmental expression of ubiquitin isopeptidases in Schistosoma mansoni

Several genes related to the ubiquitin (Ub)-proteasome pathway, including those coding for proteasome subunits and conjugation enzymes, are differentially expressed during the Schistosoma mansoni life cycle. Although deubiquitinating enzymes have been reported to be negative regulators of protein ubiquitination and shown to play an important role in Ub-dependent processes, little is known about their role in S. mansoni . In this study, we analysed the Ub carboxyl-terminal hydrolase (UCHs) proteins found in the database of the parasite’s genome. An in silico ana- lysis (GeneDB and MEROPS) identified three different UCH family members in the genome, Sm UCH-L3, Sm UCH-L5 and Sm BAP-1 and a phylogenetic analysis confirmed the evolutionary conservation of the proteins. We performed quantitative reverse transcription-polymerase chain reaction and observed a differential expression profile for all of the investigated transcripts between the cercariae and adult worm stages. These results were corroborated by low rates of Z-Arg-Leu-Arg-Gly-Gly-AMC hydrolysis in a crude extract obtained from cercariae in parallel with high Ub conjugate levels in the same extracts. We suggest that the accumulation of ubiquitinated proteins in the cercaria and early schistosomulum stages is related to a decrease in 26S proteasome activity. Taken together, our data suggest that UCH family members contribute to regulating the activity of the Ub-proteasome system during the life cycle of this parasite.