Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes.

Zika virus (ZIKV) has been extensively studied since it was linked to congenital malformations, and recent research has revealed that astrocytes are targets of ZIKV. However, the consequences of ZIKV infection, especially to this cell type, remain largely unknown, particularly considering integrative studies aiming to understand the crosstalk among key cellular mechanisms and fates involved in the neurotoxicity of the virus. Here, the consequences of ZIKV infection in iPSC-derived astrocytes are presented. Our results show ROS imbalance, mitochondrial defects and DNA breakage, which have been previously linked to neurological disorders. We have also detected glial reactivity, also present in mice and in post-mortem brains from infected neonates from the Northeast of Brazil. Given the role of glia in the developing brain, these findings may help to explain the observed effects in congenital Zika syndrome related to neuronal loss and motor deficit.

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

Anti-tumor potential and acute toxicity of Jacaranda puberula Cham. (Bignoniacea).

Cancer chemotherapy is an important strategy to treat this leading cause of death worldwide and plants may constitute a source of new antineoplastic agents. This work fractionated the ethanolic extract of Jacaranda puberula leaves and studied the in vitro antitumoral action and some toxicological effects of the most bioactive fraction. Cell lines related to worldwide cancers were used. The Dichloromethane (DCM) and PP fractions were the most bioactive ones. The anti-tumoral action of the DCM fraction was higher than that of the crude EtOH extract while that of PP fraction was higher than the original one (DCM) for both breast (MCF-7), prostate (PC3) and lung (A549) tumor cells, chronic leukemia cells. The K562 cells were the most sensitive cell line. The PP fraction (20 µg/mL) cytotoxicity for these cells was similar to that of the ursolic acid triterpene or the antineoplastic ethoposide. The PP fraction inhibited K562 cell proliferation without cell cycle arrest in a specific phase or apoptosis. PP increased the mitochondrial reduction activity of lymphocytes. After a single dose by oral route, PP fraction did not induce intrinsic acute toxicity or animal death. This work demonstrated that the J. puberula fraction (PP) present high in vitro anti-tumoral effect with no cytotoxicity for immune system cells or oral acute toxicity, improving the Jacaranda puberula ethnopharmacology and reporting new biological effects for the genus Jacaranda.