Schistosomiasis is a parasitic disease caused by several species of trematode worms and it is believed that more than 261 million people are affected worldwide. The development of new drugs has become essential due to the risk of the parasite to become resistant to Praziquantel, the only drug available for this infection. This study evaluated parasitological, immunological and histological parameters in Schistosoma mansoni infected mice treated with an herbal commercial medicine. This drug consists of menthol (30-55%) and menthone (14-32%). A 60 day treatment regimen with the herbal medicine decreased the number of S. mansoni eggs in the faeces, liver and intestine and reduced the number of hepatic granulomas. In addition, a reduction of 84% in blood eosinophilia and a decrease in the IL-4 and IL-10 blood levels after treatment, was observed. Therefore, we propose that schistosomiasis treatment with this herbal medicine, consisting of menthol and menthone, for 60 days has an immunomodulatory and anti-inflammatory action in this animal model of schistosomiasis thus contributing to the decrease in physio pathological effects caused by Schistosoma mansoni infection.

Schistosomiasis is an important parasitic disease caused by Schistosoma mansoni, an intravascular trematode. Schistosomiasis treatment is limited to just one drug, Praziquantel (PZQ). Thus, studies on new antischistosomal compounds are of fundamental importance to disease control. Here we report on the effects of Mentha piperita L. compounds – menthol and menthone – in association with acetylsalicylic acid (ASA) in the regulation of hepatic fibrosis caused by schistosomiasis granulomas. Six different groups of Swiss rats were infected with 80 cercariae. Two groups received only menthol and menthol treatment at different concentrations (30 and 50 mg/kg); two groups received treatment with the same concentration of menthol and menthol, but associated the ASA. All groups received treatment for 14 consecutive days from the 35 days after the parasitic infection. In addition, three other groups were used: uninfected and untreated group, infected and untreated group and infected group treated with the commercial drug (single dose). Parasitological, cytological and histological analyses were performed. Results showed a significant reduction on the number of eosinophils found in the peritoneal cavity lavage (LPC) in all treated groups and on the number of eosinophils found in the blood of PZQ treated group, in the blood of the group treated with 30 mg/kg of Mentaliv^® and in the blood of group treated with 50 mg/kg Mentaliv^® + ASA when compared to the infected group. All treated groups presented a reduction in the parasite load, represented by the number of S. mansoni eggs, in the experimental group treated with 30 mg/kg of menthol and menthone a 62.80% reduction was observed and in the experimental group treated with 50 mg/kg of menthol and menthone + ASA a reduction of 64.21% was observed. In the liver histological analysis we observed that all Mentaliv^® treated groups expressed a unique cytological profile, with diffused cells through the granuloma. In the experimental group treated with 50 mg/kg of Mentaliv^® + ASA it was possible to observe the formation of type III collagen fibers, a typical wound healing characteristic. Our data strongly suggest that both the hepatic fibrosis and the inflammatory process were regulated through the schistosomiasis granulomatous process after treatment with menthol and menthone associated with ASA.

Background/Aims: Titanium dioxide nanoparticles (TiO2 NPs) are extensively applied in the industry due to their photocatalytic potential, low cost, and considerably low toxicity. However, new unrelated physicochemical properties and the wide use of nanoparticles brought concern about their toxic effects. Thereby, we evaluated the cytotoxicity of a TiO2 NP composed of anatase and functionalized with sodium carboxylate ligands in a murine fibroblast cell line (LA-9). Methods: Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and ATR-FTIR spectroscopy were applied to determine nanoparticle physicochemical properties. The cell viability (MTT assay) and clonogenic survival were analyzed in fibroblasts exposed to TiO2 NP (50, 150, and 250 µg/mL) after 24h. Moreover, oxidative stress, proinflammatory state, and apoptosis were evaluated after 24h. Results: TiO2 NP characterization showed an increased hydrodynamic size (3.57 to 7.62 nm) due to solvent composition and a heterogeneity dispersion in water and cell culture media. Also, we observed a zeta potential increased from -20 to -11 mV in function of protein adsorption. TiO2 NP reduced fibroblast cell viability and induced ROS production at the highest concentrations (150 and 250 µg/mL). Moreover, TiO2 NP reduced the fibroblasts clonogenic survival at the highest concentration (250 µg/mL) on the 7th day after the 24h exposure. Nevertheless, TiO2 NP did not affect the fibroblast proinflammatory cytokines (IL-6 and TNF) secretion at any condition. Early and late apoptotic fibroblast cells were detected only at 150 µg/mL TiO2 NP after 24h. Conclusion: Probably, TiO2 NP photocatalytic activity unbalanced ROS production which induced apoptosis and consequently reduced cell viability and metabolic activity at higher concentrations.

The extensive use of titanium dioxide nanoparticles (TiO₂ NPs) in cosmetics, food, personal care products, and industries brought concerns about their possible harmful effects. Nowadays it has become important to assess TiO₂ NPs toxic effects as a way to understand their primary risks. In the cellular environment, after cell uptake, TiO₂ NPs were described to induce reactive oxygen species (ROS) production, unbalance oxidative state, and activate apoptosis in several cell lines. Therefore, we aimed to evaluate the cytotoxicity and genotoxicity of a new TiO₂ NP surface-functionalized with sodium carboxylic ligands in a murine fibroblast cell line (LA-9). TEM and DLS analysis were performed to define nanoparticle physicochemical characteristics. We evaluated the metabolic activity and LDH released after 24 h exposition to determine cytotoxic effects. Also, we evaluated DNA damage, intracellular reactive oxygen species (ROS) production, and apoptosis induction after 24 h exposure. The TiO₂ NP impaired the cell membrane integrity at 1000 μg/mL, induced intracellular ROS production and late apoptosis at 24 h. The genotoxic effects were observed at all conditions tested at 24 h. Indeed, in fibroblasts exposed at 100 μg/mL was observed early apoptosis cells. The intracellular ROS content was increased in a dose-dependent manner. Thus, short-term exposure to TiO₂ NP promoted cytotoxicity, genotoxicity and activated apoptosis pathways based on potential role of oxygen species in fibroblasts cell line.

In this study, we report the isolation and identification of an endophytic strain of Burkholderia cepacia (COPS strain) associated with Polygala paniculata roots. Polygala plants are rich sources of promising microbiomes, of which the literature reports several pharmacological effects, such as trypanocidal, antinociceptive, anesthetic, anxiolytics, and anticonvulsant activities. B. cepacia COPS belongs to a new sequence type (ST 1870) and harbors a genome estimated in 8.3Mbp which exhibits the aminoglycosides and beta-lactams resistance genes aph(3)-IIa and bla_TEM-116, respectively. Analysis performed using MLST, average nucleotide identity, and digital DNA-DNA hybridization support its species-level identification and reveals its novel housekeeping genes alleles gyrB, lepA, and phaC. The root endophyte B. cepacia COPS drew our attention from a group of 14 bacterial isolates during the primary screening for being potentially active against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Micrococcus luteus ATCC 9341, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231 and exhibited the broad-spectrum activity against phytopathogenic fungi. In addition, COPS strain showed production of protease, lipase, and esterase in solid media, and its natural product extract showed potent inhibition against fungal plant pathogens, such as Moniliophthora perniciosa, whose antagonism index (89.32) exceeded the positive control (74.17), whereas Sclerotinia sclerotiorum and Ceratocystis paradoxa showed high percentages of inhibition (85.53 and 82.69, respectively). COPS crude extract also significantly inhibited S. epidermidis ATCC 35984, E. faecium ATCC 700221 (MIC values of 32μg/mL for both), E. faecalis ATCC 29212 (64μg/mL), and S. aureus ATCC 25923 (128μg/mL). We observed moderate antagonistic activity against A. baumannii ATCC 19606 and E. coli ATCC 25922 (both at 512μg/mL), as well as potent cytotoxic effects on Leishmania infantum and Leishmania major promastigote forms with 78.25 and 57.30 inhibition. In conclusion, this study presents for the first time the isolation of an endophytic B. cepacia strain associated with P. paniculata and enough evidence that these plants may be considered a rich source of microbes for the fight against neglected diseases.