Evaluation of Cuspidaria pulchra and its Isolated Compounds Against Schistosoma mansoni Adult Worms

The present study has investigated the chemical composition of the bioactive EtOAc fraction of Cuspidaria pulchra aerial parts, as well as its schistosomicidal activities against Schistosoma mansoni adult worms in vitro. To this end, the crude ethanol extract obtained from the aerial parts of C. pulchra (Bignoniaceae) was partitioned with n-hexane, EtOAc, and n-BuOH. The EtOAc fraction was purified by preparative HPLC, which afforded 3,4-dihydroxybenzaldehyde (1), p-coumaric acid (2), p-hydroxybenzoic acid (3), ursolic acid (4), and oleanolic acid (5). The bioassay results indicated that the crude ethanol extract and the EtOAc fraction at 100 µg/mL killed the adult schistosomes in vitro. Compounds 1 and 3 at 100 µm were only able to separate coupled S. mansoni adult worms

Pictolysin-III, a Hemorrhagic Type-III Metalloproteinase Isolated from Bothrops pictus (Serpentes: Viperidae) Venom, Reduces Mitochondrial Respiration and Induces Cytokine Secretion in Epithelial and Stromal Cell Lines

From the venom of the Bothrops pictus snake, an endemic species from Peru, we recently have described toxins that inhibited platelet aggregation and cancer cell migration. In this work, we characterize a novel P-III class snake venom metalloproteinase, called pictolysin-III (Pic-III). It is a 62 kDa proteinase that hydrolyzes dimethyl casein, azocasein, gelatin, fibrinogen, and fibrin. The cations Mg2+ and Ca2+ enhanced its enzymatic activity, whereas Zn2+ inhibited it. In addition, EDTA and marimastat were also effective inhibitors. The amino acid sequence deduced from cDNA shows a multidomain structure that includes a proprotein, metalloproteinase, disintegrin-like, and cysteine-rich domains. Additionally, Pic-III reduces the convulxin- and thrombin-stimulated platelet aggregation and in vivo, it has hemorrhagic activity (DHM = 0.3 µg). In epithelial cell lines (MDA-MB-231 and Caco-2) and RMF-621 fibroblast, it triggers morphological changes that are accompanied by a decrease in mitochondrial respiration, glycolysis, and ATP levels, and an increase in NAD(P)H, mitochondrial ROS, and cytokine secretion. Moreover, Pic-III sensitizes to the cytotoxic BH3 mimetic drug ABT-199 (Venetoclax) in MDA-MB-231 cells. To our knowledge, Pic-III is the first SVMP reported with action on mitochondrial bioenergetics and may offer novel opportunities for promising lead compounds that inhibit platelet aggregation or ECM–cancer-cell interactions.</p

Genetic Diversity and Population History of a Critically Endangered Primate, the Northern Muriqui (Brachyteles hypoxanthus)

Social, ecological, and historical processes affect the genetic structure of primate populations, and therefore have key implications for the conservation of endangered species. The northern muriqui (Brachyteles hypoxanthus) is a critically endangered New World monkey and a flagship species for the conservation of the Atlantic Forest hotspot. Yet, like other neotropical primates, little is known about its population history and the genetic structure of remnant populations. We analyzed the mitochondrial DNA control region of 152 northern muriquis, or 17.6% of the 864 northern muriquis from 8 of the 12 known extant populations and found no evidence of phylogeographic partitions or past population shrinkage/expansion. Bayesian and classic analyses show that this finding may be attributed to the joint contribution of female-biased dispersal, demographic stability, and a relatively large historic population size. Past population stability is consistent with a central Atlantic Forest Pleistocene refuge. In addition, the best scenario supported by an Approximate Bayesian Computation analysis, significant fixation indices (ΦST = 0.49, ΦCT = 0.24), and population-specific haplotypes, coupled with the extirpation of intermediate populations, are indicative of a recent geographic structuring of genetic diversity during the Holocene. Genetic diversity is higher in populations living in larger areas (>2,000 hectares), but it is remarkably low in the species overall (θ = 0.018). Three populations occurring in protected reserves and one fragmented population inhabiting private lands harbor 22 out of 23 haplotypes, most of which are population-exclusive, and therefore represent patchy repositories of the species' genetic diversity. We suggest that these populations be treated as discrete units for conservation management purposes