miRNA signatures in childhood sarcomas and their clinical implications.

Progresses in multimodal treatments have significantly improved the outcomes for childhood cancer. Nonetheless, for about one-third of patients with Ewing sarcoma, rhabdomyosarcoma, or osteosarcoma steady remission has remained intangible. Thus, new biomarkers to improve early diagnosis and the development of precision-targeted medicine remain imperative. Over the last decade, remarkable progress has been made in the basic understanding of miRNAs function and in interpreting the contribution of their dysregulation to cancer development and progression. On this basis, this review focuses on what has been learned about the pivotal roles of miRNAs in the regulation of key genes implicated in childhood sarcomas.

In vitro and in vivo activities of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol against Trypanosoma cruzi.

From a series of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol screened in vitro against Trypanosoma cruzi, eight (S1 to S8) were selected for in vivo screening by single-dose oral administration (200 mg/kg of body weight) to infected mice at 5 days postinfection (dpi). Based on significant decreases in both parasitemia levels and mortality rates, S2 and S3 were selected for further assays. Despite having no in vivo effect, S1 was included since it was 2-fold more potent against trypomastigotes than megazol in vitro. Trypomastigotes treated with S1, S2, or S3 showed alterations of the flagellar structure and of the nuclear envelope. When assayed on intracellular amastigotes, the selectivity index (SI) for macrophages was in the range of >27 to >63 and for cardiac cells was >32 for S1 and >48 for megazol. In noninfected mice, S1 did not alter the levels of glutamic oxalacetic transaminase (GOT), glutamate pyruvate transaminase (GPT), or urea. S2 led to an increase in GOT, S3 to increases in GOT and GPT, and megazol to an increase in GOT. Infected mice were treated with each derivative at 50 and 100 mg/kg from dpi 6 to 15: S1 did not interfere with the course of infection or reduce the number of inflammatory foci in the cardiac tissue, S2 led to a significant decrease of parasitemia, and S3 decreased mortality. There was no direct correlation between the in vitro effect on trypomastigotes and amastigotes and the results of the treatment in experimental models, as S1 showed a high potency in vitro while, in two different schemes of in vivo treatment, no decrease of parasitemia or mortality was observed.

Chemical composition and microbicidal activity of extracts from Brazilian and Bulgarian propolis.

AIMS: The chemical composition of ethanol extracts from a Brazilian (Et-Bra) and a Bulgarian (Et-Blg) propolis, and their activity against the protozoan Trypanosoma cruzi, several fungi and bacteria species were determined. METHODS AND RESULTS: The chemical composition was determined by high temperature high resolution gas chromatography coupled to mass spectrometry. Microbiological activity was assayed in vitro against T. cruzi, Candida albicans, Sporothrix schenckii, Paracoccidioides brasiliensis, Neisseria meningitidis, Streptococcus pneumoniae and Staphylococcus aureus. CONCLUSIONS: Et-Bra and Et-Blg, although with totally distinct compositions, were active against T. cruzi and the three species of fungi. Et-Blg was more effective than Et-Bra against bacteria, particularly N. meningitidis and Strep. pneumoniae. SIGNIFICANCE AND IMPACT OF THE STUDY: Although with different classes of components, both propolis extracts showed microbicidal activity. For the bactericidal activity it was possible to establish a positive correlation with the high content of flavonoids of the Bulgarian extract.

Use of sleep questionnaires in assessing the effect of moclobemide on the sleep profiles of depressive patients.

The sleep profiles of healthy adult volunteers (group 1) were compared with the sleep profiles of depressive patients (group 2), using the method suggested by Görtelmeyer. This method uses a questionnaire to evaluate the various aspects of sleep profiles that may be different in depressive patients compared with healthy subjects. Thirty patients in group 2 were tested before and during exposure to moclobemide (450 mg/day) for 8 weeks. The group of healthy adults did not receive moclobemide and showed stable sleep profiles throughout the study period. After approximately 2 weeks of administration of moclobemide, the sleep profiles of depressive patients that had been aberrant at baseline became more normal. Around this same time, the antidepressant effects of moclobemide became apparent. The sleep questionnaire used in this study appears to be a valuable and practical method for evaluating sleep architecture.