In silico approach of secondary metabolites from Brazilian herbal medicines to search for potential drugs against SARS-CoV-2.

The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti-SARS-CoV-2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS-CoV-2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti-COVID-19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID-19 treatment.

Identification of resistance in Escherichia coli and Klebsiella pneumoniae using excitation-emission matrix fluorescence spectroscopy and multivariate analysis.

Klebsiella pneumoniae and Escherichia coli are part of the Enterobacteriaceae family, being common sources of community and hospital infections and having high antimicrobial resistance. This resistance profile has become the main problem of public health infections. Determining whether a bacterium has resistance is critical to the correct treatment of the patient. Currently the method for determination of bacterial resistance used in laboratory routine is the antibiogram, whose time to obtain the results can vary from 1 to 3 days. An alternative method to perform this determination faster is excitation-emission matrix (EEM) fluorescence spectroscopy combined with multivariate classification methods. In this paper, Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA) and Support Vector Machines (SVM), coupled with dimensionality reduction and variable selection algorithms: Principal Component Analysis (PCA), Genetic Algorithm (GA), and the Successive Projections Algorithm (SPA) were used. The most satisfactory models achieved sensitivity and specificity rates of 100% for all classes, both for E. coli and for K. pneumoniae. This finding demonstrates that the proposed methodology has promising potential in routine analyzes, streamlining the results and increasing the chances of treatment efficiency.

The effect of maternal Strongyloides venezuelensis infection on mice offspring susceptibility and immune response.

Species of Strongyloides infect a wide range of hosts worldwide. Due to their complex life cycle, it is hard to control the transmission of these parasites. Several species show evidence of vertical transmission; however, the impact of this transmission route on the susceptibility of the offspring has been poorly investigated. Herein, we used Strongyloides venezuelensis infected mice to evaluate transplacental and transmammary parasite transmission and their effect on the susceptibility of offspring. Swiss female mice were infected at the end of the gestation or during the breastfeeding period, and their offspring were examined for the presence of the parasite one week after infection of the mother. Our data showed that female mice infected with S. venezuelensis during gestation did not transmit the parasite to their offspring. On the other hand, all newborn mice breastfeeding in S. venezuelensis infected females got infected. To evaluate the effect of early exposure to the parasite on susceptibility and immune response of the hosts, the offspring of each experimental group (non-infected, gestation-infected, and breastfeeding-infected mothers) received anti-helminth treatment after parasite evaluation and were subcutaneously infected with S. venezuelensis upon reaching adulthood. Mice from the group of breastfeeding-infected mothers showed lower susceptibility to S. venezuelensis in adulthood in comparison with mice from non-infected mothers. The low parasite burden was accompanied by earlier eosinophil and neutrophil activation in the gut and higher serum levels of IgE. In contrast, S. venezuelensis infection in adult mice born from gestation-infected mothers presented with more worms in the intestine and lower levels of parasite-reactive IgM in serum in comparison with mice born from non-infected mothers, thus suggesting that early exposure to parasite antigens may modulate the protective immune response. Altogether, our data confirmed transmammary, but not transplacental, transmission of S. venezuelensis in mice and demonstrated that early exposure to the parasite and/or their antigens has an important effect on host susceptibility to a later infection.

Inclusion of discarded banana in sugarcane silage decreases dry matter losses and improves its nutritional value / La inclusión de banano de descarte en el ensilaje de caña de azúcar reduce las pérdidas de materia seca y mejora su valor nutricional / A inclusão de banana de descarte em silagem de cana de açúcar decresce as perdas de matéria seca e melhora o seu valor nutricional

Abstract Background: Sugarcane silage (SCS) has often been characterized by large dry matter (DM) losses associated with reduction in soluble nutrients and increase in indigestible fiber. Objective: To evaluate the effect of including discarded fruits on the losses and nutritional value in SCS. Methods: A completely randomized design was used with five treatments and five replications. Silages were added with 15% (as-fed basis) papaya (Carica papaya) (SP), acerola (Malpighia glabra) (SA), banana (Musa sp.) (SB) or tomato (Solanum lycopersicum) (ST). The control treatment was composed only of SCS. Twenty-five (25-L) plastic buckets were used to make the experimental silos, which were opened on the 90th day after their closure. Data were analyzed by analysis of variance. Results: Gas losses and total DM losses were lower and DM recovery was higher in SB and SA than in the control (p<0.05). The SB had lower content of neutral detergent fiber and acid detergent fiber compared to SP, SA, ST and the control group (p<0.05). There was no effect of treatment for ethanol content (p>0.05). However, there was treatment effect for lactic and acetic acids, ammonia nitrogen contents, lactic acid bacteria, and yeasts and mold counts (p<0.05). Conclusion: The inclusion of 15% banana or acerola in SCS decreases losses and increases DM recovery. Furthermore, the inclusion of 15% banana improves the nutritional value of SCS.

Resumen Antecedentes: El ensilaje de caña de azúcar (SCS) es frecuentemente caracterizado por grandes pérdidas de materia seca (DM) asociadas con reducciones en los nutrientes solubles y aumentos en la fibra indigestible. Objetivo: Evaluar el efecto de la inclusión de frutas de descarte sobre las perdidas y el valor nutricional del SCS. Métodos: Se utilizó un diseño completamente aleatorizado con cinco tratamientos y cinco repeticiones. Fueron adicionados a los ensilajes, 15 % (materia natural) de papaya (Carica papaya) (SP), acerola (Malpighia glabra) (SA), banano (Musa sp.) (SB) o tomate (Solanum lycopersicum) (ST). El control estuvo compuesto apenas por SCS. Veinticinco baldes de 25 L fueron usados para hacer los silos, los cuales se abrieron al día 90 posterior a su cierre. Los datos fueron analizados por análisis de varianza. Resultados: Las pérdidas de gases y de DM total fueron menores y la recuperación de DM fue mayor en SB y SA que en el grupo control (p<0,05). Los contenidos de fibra detergente neutra y ácida fueron menores en SB comparados con SP, SA, ST y el grupo control (p<0,05). No hubo efecto para el contenido de etanol (p>0,05). Sin embargo, hubo efecto de tratamiento para los contenidos de ácidos láctico y acético, y nitrógeno amoniacal y recuento de bacterias ácido lácticas, levaduras y hongos (p<0,05). Conclusiones: La inclusión de 15% de banano y acerola en SCS decreció las perdidas, y aumentó la recuperación de DM. Además, la inclusión de un 15% de banano mejoró el valor nutricional de SCS.

Resumo Antecedentes: A silagem de cana de açúcar (SCS) é frequentemente caracterizada por grandes perdas de matéria seca (DM) associadas com reduções nos nutrientes solúveis e aumento na fibra indigestível. Objetivo: Avaliar o efeito da inclusão de frutas de descarte sobre as perdas e o valor nutricional de SCS. Métodos: Um delineamento completamente casualizado foi utilizado, com cindo tratamentos e cinco repetições. As silagens foram adicionadas com 15% (matéria natural) de mamão (Carica papaya) (SP), acerola (Malpighia glabra) (SA), banana (Musa sp.) (SB) ou tomate (Solanum lycopersicum) (ST). O controle foi composto apenas por SCS. Vinte e cinco baldes de 25 L foram usados para fazer os silos, que foram abertos no 90º dia após o fechamento deles. Os dados foram analisados por meio de análise de variância. Resultados: As perdas por gases e de DM total foram menores e a recuperação de DM foi maior em SB e SA que no controle (p<0,05). Os conteúdos de fibra em detergente neutro e ácido foram menores em SB comparado a SP, SA, ST e o grupo de controle (p<0,05). Não houve efeito para conteúdo de etanol (p>0,05). Contudo, houve efeito de tratamento para os conteúdos de ácidos lático e acético, e nitrogênio amoniacal e contagens de bactérias láticas, e leveduras e fungos (p<0,05). Conclusões: A inclusão de 15% de banana e acerola em SCS decresceu as perdas, e aumentou a recuperação de DM. Adicionalmente, a inclusão de 15% de banana melhorou o valor nutricional da SCS.

On the synergy between silver nanoparticles and doxycycline towards the inhibition of Staphylococcus aureus growth.

In a previous paper (RSC Adv., 2015, 5, 66886-66893), we showed that the combination of silver nanoparticles (NanoAg) with doxycycline (DO) culminated in an increased bactericidal activity towards E. coli. Herein we further investigated the metabolic changes that occurred on Staphylococcus aureus upon exposure to NanoAg with the help of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) coupled with multivariate data analysis. It has been discovered that the combination of DO with NanoAg produced metabolic changes in S. aureus that were not simply the overlap of the treatments with DO and NanoAg separately. Our results suggest that DO and NanoAg act synergistically to impede protein synthesis by the bacteria.

Thromboelastographic assessment of the impact of mexiletine on coagulation abnormalities induced by air or normal saline intravenous injections in conscious rats.

BACKGROUND: Thromboelastography (TEG) in venous air embolism (VAE) has been poorly studied. We induced coagulation abnormalities by VAE in a rat model, assessed by TEG with and without mexiletine, a lidocaine analogue local anesthetic. METHODS: Twenty-three Sprague Dawley rats instrumented under isoflurane anesthesia and allowed to recover five days prior to the experiments were randomized into three experimental groups: 1) VAE (n = 6); 2) VAE and mexiletine (n = 9); and 3) normal saline (NS) alone (control group, n = 8). Blood samples were collected at baseline, one hour (h) and 24 h in all groups and analyzed by TEG to record the R, K, angle α and MA parameters. RESULTS: In Group 1, VAE decreased significantly R at 1 h (31%), K at 1 h (59%) and 24 h (34%); α increased significantly at 1 h (30%) and 24 h (22%). While R returned to baseline values within 24 h, K, MA and α did not. In group-2 (Mexiletine + VAE), K and R decreased at 1 h (48% and 29%, respectively) and at 24 h the changes were non-significant. Angle α increased at 1 h (28%) and remained increased for 24 h (25%). In group 3 (NS), only R was temporarily affected. MA increased significantly at 24 h only in the VAE alone group. CONCLUSION: As expected, VAE produced a consistent and significant hypercoagulable response diagnosed/confirmed by TEG. Mexiletine prevented the MA elevation seen with VAE and corrected R and K time at 24 h, whereas angle α remained unchanged. Mexiletine seemed to attenuate the hypercoagulability associated with VAE in this experiment. These results may have potential clinical applications and deserve further investigation.

Preparation of pellets containing Pothomorphe umbellata extracts by extrusion-spheronization: improvement of 4-nerolidylcatechol photostability

Pothomorphe umbellata (L.) Miq., Piperaceae, has been extensively used in Brazilian folk medicine and it is well known for its strong antioxidant properties. However, its main active constituent, 4-nerolydilcatechol (4-NC), is sensitive to ultraviolet and visible light, which can limit the use of intermediate and final herbal preparations of this species. In the present work, coated multiparticulate solid dosage forms of P. umbellata were obtained with the purpose of increasing the stability of 4-NC. P. umbellata extract was used as a wetting liquid for the preparation of pellets by extrusion-spheronization. Pellets were coated in a fluidized bed by three different polymers (hydroxypropylmethylcellulose (HPMC), polyvynilpirrolidone K-30 (PVP-K30), and polyvinyl alcohol-polyethylene glycol graft-copolymer (PVAPEG)). 4-NC photostability was evaluated by an accelerated photostability protocol. Pellets showed a narrow size distribution and low friability. 4-NC photodegradation followed a second order degradation kinetics with similar k values for the percolate, uncoated pellets and HPMC coated pellets. Photoprotection was higher in pellets coated with PVP-K30 and PVA-PEG. PVA-PEG coated pellets with 6 and 9% weight gain resulted in a final concentration of 4-NC approximately cinco times higher than uncoated pellets or liquid extracts, suggesting the potential of this formulation as a multiparticulate solid dosage form for P. umbellata extracts.

The feeding process of Cimex lectularius (Linnaeus 1758) and Cimex hemipterus (Fabricius 1803) on different bloodmeal sources.

The bedbugs Cimex lectularius and Cimex hemipterus are obligate hematophages in all their nymphal instars as well as in the adult stage. The efficiency with which the insects obtain blood from their hosts is directly related to their population dynamics. In the present study we compared the feeding process and salivary content in individuals of these two species when fed on different blood sources or host sites, using a cibarial pump electromyogram. Females ingested more blood than males but needed longer contact time with the host to complete the meal. The bedbug C. lectularius was more efficient than C. hemipterus in obtaining blood from mice and pigeons. With regard to the feeding site on mice, it was easier for the insects to obtain blood from the skin of the belly than that of the back. Individuals of C. hemipterus were able to maintain the cibarial pump functioning at higher frequencies for longer periods when fed on pigeons treated with anticoagulant. Although saliva from C. lectularius contained more hemeproteins and showed more anti-clotting activity its total protein content was similar to that of C. hemipterus. Overall, C. lectularius obtains a bloodmeal more efficiently from its hosts, which may have enabled this species to reach higher levels of infestation than C. hemipterus.