Analysis of Proteasomal Proteolysis during the In Vitro Metacyclogenesis of Trypanosoma cruzi

Proteasomes are large protein complexes, whose main function is to degrade unnecessary or damaged proteins. The inhibition of proteasome activity in Trypanosoma cruzi blocks parasite replication and cellular differentiation. We demonstrate that proteasome-dependent proteolysis occurs during the cellular differentiation of T. cruzi from replicative non-infectious epimastigotes to non-replicative and infectious trypomastigotes (metacyclogenesis). No peaks of ubiquitin-mediated degradation were observed and the profile of ubiquitinated conjugates was similar at all stages of differentiation. However, an analysis of carbonylated proteins showed significant variation in oxidized protein levels at the various stages of differentiation and the proteasome inhibition also increased oxidized protein levels. Our data suggest that different proteasome complexes coexist during metacyclogenesis. The 20S proteasome may be free or linked to regulatory particles (PA700, PA26 and PA200), at specific cell sites and the coordinated action of these complexes would make it possible for proteolysis of ubiquitin-tagged proteins and oxidized proteins, to coexist in the cell

Transcriptional Profile and Structural Conservation of SUMO-Specific Proteases in Schistosoma mansoni

Small ubiquitin-related modifier (SUMO) is involved in numerous cellular processes including protein localization, transcription, and cell cycle control. SUMOylation is a dynamic process, catalyzed by three SUMO-specific enzymes and reversed by Sentrin/SUMO-specific proteases (SENPs). Here we report the characterization of these proteases in Schistosoma mansoni. Using in silico analysis, we identified two SENPs sequences, orthologs of mammalian SENP1 and SENP7, confirming their identities and conservation through phylogenetic analysis. In addition, the transcript levels of Smsenp1/7 in cercariae, adult worms, and in vitro cultivated schistosomula were measured by qRT-PCR. Our data revealed upregulation of the Smsenp1/7 transcripts in cercariae and early schistosomula, followed by a marked differential gene expression in the other analyzed stages. However, no significant difference in expression profile between the paralogs was observed for the analyzed stages. Furthermore, in order to detect deSUMOylating capabilities in crude parasite extracts, SmSENP1 enzymatic activity was evaluated using SUMO-1-AMC substrate. The endopeptidase activity related to SUMO-1 precursor processing did not differ significantly between cercariae and adult worms. Taken together, these results support the developmentally regulated expression of SUMO-specific proteases in S. mansoni

Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

Several previous studies correlated immunopathological aspects of canine visceral leishmaniasis (CVL) with tissue parasite load and/or the clinical status of the disease. Recently, different aspects of the immune response in Leishmania-infected dogs have been studied, particularly the profile of cytokines in distinct compartments. However, the role of chemokines in disease progression or parasite burdens of the visceralising species represents an important approach for understanding immunopathology in CVL. We found an increase in inflammatory infiltrate, which was mainly composed of mononuclear cells, in the skin of animals presenting severe forms of CVL and high parasite density. Our data also demonstrated that enhanced parasite density is positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. These findings represent an advance in the knowledge of the involvement of skin inflammatory infiltrates in CVL and the systemic consequences and may contribute to developing a rational strategy for the design of new and more efficient prophylactic tools and immunological therapies against CVL

Evidências sobre o uso de leite materno no tratamento dermatológico da pele do recém-nascido: Evidence on the use of breast milk in the dermatological treatment of newborn skin

O presente estudo tem como objetivo analisar as evidências sobre o uso de leite materno no tratamento dermatológico da pele do recém-nascido. A pesquisa foi desenvolvida com base em uma Revisão Sistemática da Literatura (RSL). A pesquisa foi realizada na Biblioteca Virtual do Ministério da Saúde (BVS) que indexa artigos de diferentes bases de dados como Scielo, Lilacs e MedLine e na PubMed.  Como critérios de inclusão foi considerado ser disponível em formato completo e publicado nos últimos dez anos (2012-2022). Foram excluídos estudos que não respondessem o tema de pesquisa ou que estivessem duplicados nas bases de dados. O uso do leite materno como tratamento dermatológico de pele é potencial, porém, os estudos ainda são escassos e inconclusivos, fazendo-se importante que estudos sejam realizados para que se possa sanar dúvidas sobre o uso do leite materno, considerando ser um tratamento natural e de baixo custo

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

RESEARCH NOTE - Lactate Dehydrogenase: Sequence and Analysis of its Expression during the Life Cycle of Schistosoma mansoni

Schistosoma mansoni is one of the causative agents of schistosomiasis, a parasite disease affecting 200 million people. Schistosomes are the only trematodes which are sexually dimorphic. During their development, the parasite undergo profound morphological and biochemical changes. Free-living cercarial emerge from their invertebrate snail host into fresh water using oxidative glucose metabolism to provide high energy levels in their efforts to find and penetrate into a final vertebrate host. During the host invasion cercariae loses their tails and transforms into schistosomula. Biochemical studies suggest that this transformation is accompained by a transition from an aerobic to a more anaerobic energy metabolism. In the vertebrate blood stream the schistosomula develop into adult worms which generate large amounts of lactate using an anaerobic metabolism

Genome-wide identification of novel micrornas and their target genes in the human parasite schistosoma mansoni

Mature microRNAs (miRNAs) are small, non-coding regulatory RNAs which can elicit post-transcriptional repression of mRNA levels of target genes. Here, we report the identification of 67 mature and 42 precursor miRNAs in the Schistosoma mansoni parasite. The evolutionarily conserved S. mansoni miRNAs consisted of 26 precursor miRNAs and 35 mature miRNAs, while we identified 16 precursor miRNAs and 32 mature miRNAs that displayed no conservation. These S. mansoni miRNAs are located on seven autosomal chromosomes and a sex (W) chromosome. miRNA expansion through gene duplication was suggested for at least two miRNA families miR-71 and mir-2. miRNA target finding analysis identified 389 predicted mRNA targets for the identified miRNAs and suggests that the sma-mir-71 may be involved in female sexual maturation. Given the important roles of miRNAs in animals, the identification and characterization of miRNAs in S. mansoni will facilitate novel approaches towards prevention and treatment of Schistosomiasis

Comparing lactate and glycerol as a single-electron donor for sulfate reduction in fluidized bed reactors.

Among the greatest challenges to the full implementation of biological sulfate reduction are the cost and availability of the electron source. With the development of the biofuel industry, new organic substrates have become available. Therefore, this work sought to compare the performance of a sulfidogenic process utilizing either lactate or glycerol as the substrate for sulfate-reducing bacteria (SRB) growth. Although sulfate reduction is energetically more favorable with lactate, glycerol is a less expensive alternative because excess production is forecasted with the worldwide development of the biodiesel industry. Continuous experiments were performed in a fluidized bed (FB) reactor containing activated carbon as a carrier for a mixed bacterial population composed of sulfate-reducing and fermentative bacteria. During the lactate-fed phases, incomplete oxidation of lactate to acetate by SRB was the dominant metabolic pathway resulting in as much as 90 % sulfate reduction and high acetate concentrations (2.7 g L-1). Conversely, in the glycerol-fed phases, glycerol degradation resulted from syntrophic cooperation between sulfate-reducing and fermentative bacteria that produce butyrate along with acetate (1.0 g L-1) as oxidation products. To our knowledge, this is the first report of butyrate formation during sulfate reduction in a glycerol-fed continuousflow reactor. Sulfate concentrations were reduced by about 90 % (from 2,000 to 100–300 mg L-1) when glycerol was being fed to the reactor. Since the FB reactor was able to stand a change from lactate to glycerol, this reactor is recommended as the preferred option should glycerol be selected as a cost-effective alternative to lactate for continuous sulfate reduction