Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC).Evidence favoring a causative role for ZIKV in microcephaly has emerged and was the object of several publications. For instance, ZIKV was detected in the amniotic fluids of two fetuses that presented microcephaly, which strongly suggests intrauterine transmission 7 . In addition, detection of the virus together with numerous alterations in the brain of an aborted fetus, while the virus was not detected in any other fetal tissue, also suggested a neurotropism 8 . Epidemiological data showed varied percentage of risk of microcephaly when infection occurs in the first trimester in different geographical locations, suggesting that other factors such as virus strain and co-infections may also contribute to the development of congenital defects 9 . Therefore, the understanding of the mechanisms involved in the neurotoxicity caused by ZIKV is of great relevance.Studies in animal models have also reinforced the link between ZIKV infection and congenital malformations 10-12 . These, however, do not reproduce properly the human infection, since mice are resistant to ZIKV

The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4′-methylbipyridine (Me-bipy) and 4,4′-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3- The Ru(III) complex, [RuCl 2 (Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh 3 ) 2 (bipy)]PF 6 and [RuCl 2 (Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl 2 (Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs.

Leishmaniasis are diseases caused by parasites belonging to Leishmania genus. The treatment with pentavalent antimonials present high toxicity. Secondary line drugs, such as amphotericin B and miltefosine also have a narrow therapeutic index. Therefore, there is an urgent need to develop new drugs to treat leishmaniasis. Here, we present the in vitro anti-leishmanial activity of unusual dimeric flavonoids purified from Arrabidaea brachypoda. Three compounds were tested against Leishmana sp. Compound 2 was the most active against promastigotes. Quantifying the in vitro infected macrophages revealed that compound 2 was also the most active against intracellular amastigotes of L. amazonensis, without displaying host cell toxicity. Drug combinations presented an additive effect, suggesting the absence of interaction between amphotericin B and compound 2. Amastigotes treated with compound 2 demonstrated alterations in the Golgi and accumulation of vesicles inside the flagellar pocket. Compound 2-treated amastigotes presented a high accumulation of cytoplasmic vesicles and a myelin-like structure. When administered in L. amazonensis-infected mice, neither the oral nor the topical treatments were effective against the parasite. Based on the high in vitro activity, dimeric flavonoids can be used as a lead structure for the development of new molecules that could be useful for structure-active studies against Leishmania.

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis and inflammation are hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples obtained from C57Bl/6 mice chronically infected with T. cruzi and serum samples collected from CCC patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gain-and loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGFβ1) and T. cruzi stimulation, while miR-21 blockage reduced collagen expression. Finally, treatment of T. cruzi-infected mice with locked nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC.