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We present the case of a 35-year-old male with a first-degree family history of gastric cancer (his father was diagnosed at the age of 45), who was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a complex disease caused by infection with different Leishmania parasites. The number of medications used for its treatment is still limited and the discovery of new drugs is a valuable approach. In this context, here we describe the in vitro leishmanicidal activity and the in silico interaction between trypanothione reductase (TryR) and (-)-5-demethoxygrandisin B from the leaves of Virola surinamensis (Rol.) Warb. The compound (-)-5-demethoxygrandisin B was isolated from V. surinamensis leaves, a plant found in the Brazilian Amazon, and it was characterized as (7R,8S,7′R,8′S)-3,4,5,3′,4′-pentamethoxy-7,7′-epoxylignan. In vitro antileishmanial activity was examined against Leishmania amazonensis, covering both promastigote and intracellular amastigote phases. Cytotoxicity and nitrite production were gauged using BALB/c peritoneal macrophages. Moreover, transmission electron microscopy was applied to probe ultrastructural alterations, and flow cytometry assessed the shifts in the mitochondrial membrane potential. In silico methods such as molecular docking and molecular dynamics assessed the interaction between the most stable configuration of (-)-5-demethoxygrandisin B and TryR from L. infantum (PDB ID 2JK6). As a result, the (-)-5-demethoxygrandisin B was active against promastigote (IC50 7.0 µM) and intracellular amastigote (IC50 26.04 µM) forms of L. amazonensis, with acceptable selectivity indexes. (-)-5-demethoxygrandisin B caused ultrastructural changes in promastigotes, including mitochondrial swelling, altered kDNA patterns, vacuoles, vesicular structures, autophagosomes, and enlarged flagellar pockets. It reduced the mitochondria membrane potential and formed bonds with important residues in the TryR enzyme. The molecular dynamics simulations showed stability and favorable interaction with TryR. The compound targets L. amazonensis mitochondria via TryR enzyme inhibition. [ABSTRACT FROM AUTHOR]

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3β,7β-dihydroxyacanthoic acid (S1). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1. [ABSTRACT FROM AUTHOR]

Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC50 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC50 476.0 µg/mL) and HepG2 (CC50 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

The present work reports the isolation and biological evaluation of three dimeric xanthones from Paecilomyces sp. EJC01.1 isolated as endophytic from Schnella splendens, a typical plant of the Amazon. The compounds phomoxanthone A (1), phomoxanthone B (2) and dicerandrol B (3) were isolated by chromatographic procedures and identified by spectroscopic methods of 1D and 2D NMR and MS. The extracts and compound 1 showed antimicrobial activities against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Pseudomonas aeruginosa. The compound phomoxanthone A (1) showed greater inhibitory activity against B. subtilis (MIC of 7.81 µg mL−1); in addition, it also pronounced inhibitory effect against promastigote forms of Leishmania amazonensis (IC50 of 16.38 ± 1.079 µg mL−1) and epimastigote forms Trypanosoma cruzi (IC50 of 28.61 ± 1.071 µg mL−1). To provide more information about the antibacterial activity of compound 1, an unprecedented molecular docking study was performed using S-ribosyl-homocysteine lyase (LuxS) (PDB ID 2FQO), which showed a possible interaction of phomoxanthone A with two of the residues (His58 and Cys126) that are fundamental for the catalysis mechanism in B. subtilis, which may be associated with the higher activity, when compared to other bacteria, observed in experimental studies. Additionally, quantum studies (DFT) were performed, for which a low gap value (5.982 eV) was observed, which corroborates the reactivity of phomoxanthone A. Thus, phomoxanthone A can be a good agent against pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Carajurin is the main constituent of Arrabidaea chica species with reported anti-Leishmania activity. However, its mechanism of action has not been described. This study investigated the mechanisms of action of carajurin against promastigote forms of Leishmania amazonensis. Carajurin was effective against promastigotes with IC50 of 7.96 ± 1.23 μg.mL−1 (26.4 µM), and the cytotoxic concentration for peritoneal macrophages was 258.2 ± 1.20 μg.mL−1 (856.9 µM) after 24 h of treatment. Ultrastructural evaluation highlighted pronounced swelling of the kinetoplast with loss of electron-density in L. amazonensis promastigotes induced by carajurin treatment. It was observed that carajurin leads to a decrease in the mitochondrial membrane potential (p = 0.0286), an increase in reactive oxygen species production (p = 0.0286), and cell death by late apoptosis (p = 0.0095) in parasites. Pretreatment with the antioxidant NAC prevented ROS production and significantly reduced carajurin-induced cell death. The electrochemical and density functional theory (DFT) data contributed to support the molecular mechanism of action of carajurin associated with the ROS generation, for which it is possible to observe a correlation between the LUMO energy and the electroactivity of carajurin in the presence of molecular oxygen. All these results suggest that carajurin targets the mitochondria in L. amazonensis. In addition, when assessed for its drug-likeness, carajurin follows Lipinski"s rule of five, and the Ghose, Veber, Egan, and Muegge criteria. [ABSTRACT FROM AUTHOR]

This work studies the feasibility of using mental attention to access a computer. Brain activity was measured with an electrode placed at the Fp1 position and the reference on the left ear; seven normally developed people and three subjects with cerebral palsy (CP) took part in the experimentation. They were asked to keep their attention high and low for as long as possible during several trials. We recorded attention levels and power bands conveyed by the sensor, but only the first was used for feedback purposes. All of the information was statistically analyzed to find the most significant parameters and a classifier based on linear discriminant analysis (LDA) was also set up. In addition, 60% of the participants were potential users of this technology with an accuracy of over 70%. Including power bands in the classifier did not improve the accuracy in discriminating between the two attentional states. For most people, the best results were obtained by using only the attention indicator in classification. Tiredness was higher in the group with disabilities (2.7 in a scale of 3) than in the other (1.5 in the same scale); and modulating the attention to access a communication board requires that it does not contain many pictograms (between 4 and 7) on screen and has a scanning period of a relatively high tscan ≈ 10 s. The information transfer rate (ITR) is similar to the one obtained by other brain computer interfaces (BCI), like those based on sensorimotor rhythms (SMR) or slow cortical potentials (SCP), and makes it suitable as an eye-gaze independent BCI. [ABSTRACT FROM AUTHOR]

The natural compound ravenelin was isolated from the biomass extracts of Exserohilum rostratum fungus, and its antimicrobial, antiplasmodial, and trypanocidal activities were evaluated. Ravenelin was isolated by column chromatography and HPLC and identified by NMR and MS. The susceptibility of Gram-positive and Gram-negative bacteria strains to ravenelin was determined by microbroth dilution assay. Cytotoxicity was evaluated in hepatocarcinoma cells (HepG2) and BALB/c peritoneal macrophages by using MTT. SYBR Green I-based assay was used in the asexual stages of Plasmodium falciparum. Trypanocidal activity was tested against the epimastigote and intracellular amastigote forms of Trypanosoma cruzi. Ravenelin was active against Gram-positive bacteria strains, with emphasis on Bacillus subtilis (MIC value of 7.5 µM). Ravenelin's antiparasitic activities were assessed against both the epimastigote (IC50 value of 5 ± 1 µM) and the intracellular amastigote forms of T. cruzi (IC50 value of 9 ± 2 µM), as well as against P. falciparum (IC50 value of 3.4 ± 0.4 µM). Ravenelin showed low cytotoxic effects on both HepG2 (CC50 > 50 µM) and peritoneal macrophage (CC50 = 185 ± 1 µM) cells with attractive selectivity for the parasites (SI values > 15). These findings indicate that ravenelin is a natural compound with both antibacterial and antiparasitic activities, and considerable selectivity indexes. Therefore, ravenelin is an attractive candidate for hit-to-lead development. [ABSTRACT FROM AUTHOR]

Aniba rosaeodora is one of the most widely used plants in the perfumery industry, being used as medicinal plant in the Brazilian Amazon. This work aimed to evaluate the chemical composition of A. rosaeodora essential oil and its biological activities. A. rosaeodora essential oil presented linalool (93.60%) as its major compound. The A. rosaeodora essential oil and linalool showed activity against all the bacteria strains tested, standard strains and marine environment bacteria, with the lower minimum inhibitory concentration being observed for S. aureus. An efficient antioxidant activity of A. rosaeodora essential oil and linalool (EC50: 15.46 and 6.78 µg/mL, respectively) was evidenced by the inhibition of the 2,2-azinobis- (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. The antitrypanosomal activity of A. rosaeodora essential oil and linalool was observed at high concentrations against epimatigote forms (inhibitory concentration for 50% of parasites (IC50): 150.5 ± 1.08 and 198.6 ± 1.12 µg/mL, respectively), and even higher against intracellular amastigotes of T. cruzi (IC50: 911.6 ± 1.15 and 249.6 ± 1.18 µg/mL, respectively). Both A. rosaeodora essential oil and linalool did not exhibit a cytotoxic effect in BALB/c peritoneal macrophages, and both reduced nitrite levels in unstimulated cells revealing a potential effect in NO production. These data revealed the pharmacological potential of A. rosaeodora essential oil and linalool, encouraging further studies. [ABSTRACT FROM AUTHOR]

Arrabidaea chica Verlot (crajiru) is a plant used in folk medicine as an astringent, anti-inflammatory, wound healing and to treat fungal and viral diseases such as measles chickenpox and herpes. Arrabidaea chica has several morphotypes recognized but little is known about its chemical variability. In the present study the anthocyanidin profile of A. chica morphotypes collected in two seasons (summer and winter) have been examined and their activity against Leishmania infection compared. High-performance liquid chromatography coupled to a diode-array detector (HPLC-DAD-UV) and by tandem mass spectrometry with electrospray ionization (ESI-MS/MS) were used for anthocyanidin separation and identification. Antileishmanial activity was measured against promastigote forms of Leishmania amazonensis. Multivariate analysis, principal component analysis (PCA) and Pearson's correlation were performed to classify morphotypes accordingly to their anthocyanidin profile. The presence of 6,7,3′,4′-tetrahydroxy-5-methoxyflavylium (3′-hydroxy-carajurone) (1), carajurone (2), 6,7,3′-trihydroxy-5,4′-dimethoxy-flavylium (3′-hydroxy-carajurin) (3) and carajurin (4), and three unidentified anthocyanidins were detected. Two different groups were recognized: group I containing 3′-hydroxy-carajurone; and group II with high content of carajurin. Among anthocyanidins identified in the extracts, only carajurin showed significant statistical correlation (p = 0.030) with activity against L. amazonensis. Carajurin could thus be considered as a pharmacological marker for the antileishmanial potential of the species. [ABSTRACT FROM AUTHOR]