Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC50) of 0.247 µmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC50) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

HLA-G 5' URR SNPs and 3' UTR 14-bp insertion/deletion polymorphism in an Afro-Brazilian population from Paraná State.

The present study investigated 23 SNPs in the 5'URR promoter region and the 14 bp ins/del polymorphism at the 3'UTR region of the HLA-G gene in 150 individuals with Afro-Brazilian ancestry. Three haplotypes were found to be the most frequent. Comparing these polymorphisms in other samples, our data suggest that Afro-Brazilians are more similar to the Euro-Brazilians than to Hutterite population.

Phytotherapy: an introduction to its history, use and application / Fitoterapia: introdução a sua história, uso e aplicação

There has been a great advance in the pharmacognosy field, which has increased the use of medicinal plants by health professionals and practitioners of folk medicine. This systematic review explored the history and the present day application of phytotherapeutic medicines. We searched the databases Cochrane Library, Embase, Lilacs, PubMed, Scielo and a specialized bibliography. We concluded that there are many therapeutic potentialities in the use of phytotherapeutic medicines and medicinal plants. We also concluded that despite the increasing number of publications in the field each year, there is still a lack of reviews and meta-analyses that could promote a better integration of the knowledge produced. In addition, research about pharmacological interactions and multidisciplinary studies may promote a quicker and safer process from the workbench up to the clinical trials.

Diante do avanço que vem ocorrendo na área da farmacognosia, decorrente do aumento do uso de plantas medicinais na medicina popular e por profissionais da saúde, este trabalho apresenta uma revisão sistemática sobre a história dos fitoterápicos e sobre sua aplicação na atualidade. Foram realizadas buscas nas bases de dados Cochrane Library, Embase, Lilacs, PubMed, Scielo e em bibliografia especializada. Concluiu-se que, apesar da quantidade de estudos publicados crescer a cada ano, há ainda escassez de revisões e meta-análises que promovam melhor integração do conhecimento produzido. Pesquisas contemplando interações farmacológicas e trabalhos multidisciplinares podem acelerar os estudos em bases mais seguras, desde a bancada até os ensaios clínicos.

Assessment of antimicrobial activity in vitro of ethanolic extracts of Banisteriopsis anisandra (A. Juss. ) B. Gates (Malpighiaceae) / Avaliação da atividade antimicrobiana in vitro de extratos etanólicos de Banisteriopsis anisandra (A. Juss. ) B. Gates (Malpighiaceae)

The aim of this study was to evaluate the antimicrobial activity in vitro of ethanolic extracts of Banisteriopsis anisandra. Tests were performed using the extracts overlay method in the culture medium for phytopathogenic fungi Rhizoctonia solani and Fusarium oxysporum, and disk diffusion for the microorganisms Staphylococcus aureus and Candida albicans. Ethanolic extracts from leaves were prepared by maceration (extract I) and decoction (extract II) at 430.0, 215.0 and 107.5 mg/mL. The growth inhibition of R. solani and F. oxysporum was determined by calculating the mycelia growth speed rate (MGSR) and, in relation C. albicans and S. aureus, it was determined by measuring the inhibition halos. Extracts that caused significant inhibition were also tested at 86.0, 64.5, 43.0 and 21.5 mg/mL for C. albicans and S. aureus. Both extracts showed inhibitory activity on the microorganisms studied. Rizoctonia solani showed lower MGSR in the presence of extract II (107.5 mg/mL) and Fusarium oxysporum showed slight MGSR reduction in the presence of extract I (107.5 mg/mL) and II (107.5 and 215 mg/mL). Ethanolic extracts I and II inhibited the growth of C. albicans, with the highest rates of inhibition observed in the presence of extract II (215.0 mg/mL). For S. aureus, the highest inhibitory activity was observed in the presence of ethanolic extract II, prepared by decoction at 430.0 mg/mL. Results showed a promising antimicrobial activity of extracts of B. anisandra, which may contribute to further studies leading to a future development of medicines to treat human and plant diseases caused by these organisms.

O objetivo deste estudo foi avaliar a atividade antimicrobiana in vitro de extratos etanólicos de Banisteriopsis anisandra. Os testes foram realizados utilizando o método de sobreposição de extratos em meio de cultura para fungos fitopatogênicos Rhizoctonia solani e Fusarium oxysporum e de difusão em disco para os microrganismos Staphylococcus aureus e Candida albicans. Foram testados de extratos etanólicos de folhas preparados por maceração (extrato I) e decocção (extrato II), nas concentrações de 430,0; 215,0 e 107,5 mg/mL. A inibição do crescimento de R. solani e F. oxysporum foi determinada pelo cálculo do índice de velocidade de crescimento micelial (IVCM) e de C. albicans e S. aureus, por meio da medida da halos de inibição. Os extratos que causaram inibição significativa também foram testados nas concentrações de 86,0; 64,5; 43,0 e 21,5 mg/mL para C. albicans e S. aureus. Ambos os extratos mostraram atividade inibitória sobre os microrganismos estudados. Rizoctonia solani apresentou menor IVCM na presença do extrato II (107,5 mg/mL) e Fusarium oxysporum apresentou discreta redução no IVCM na presença do extrato I (107,5 mg/mL) e II (107,5 e 215 mg/mL). Extratos etanólicos I e II inibiram o crescimento de C. albicans, com as maiores taxas de inibição observadas na presença do extrato II (215,0 mg/mL). Para S. aureus a maior atividade inibitória foi observada na presença do extrato II, na concentração de 430 mg/mL. Os resultados mostraram promissora atividade antimicrobiana de extratos de B. anisandra, o que pode contribuir para estudos futuros visando o desenvolvimento de medicamentos para doenças humanas e de plantas causadas por estes microrganismos.

Plasma cytokine response, lipid peroxidation and NF-kB activation in skeletal muscle following maximum progressive swimming

Our objective was to determine lipid peroxidation and nuclear factor-κB (NF-κB) activation in skeletal muscle and the plasma cytokine profile following maximum progressive swimming. Adult male Swiss mice (N = 15) adapted to the aquatic environment were randomly divided into three groups: immediately after exercise (EX1), 3 h after exercise (EX2) and control. Animals from the exercising groups swam until exhaustion, with an initial workload of 2 percent of body mass attached to the tail. Control mice did not perform any exercise but were kept immersed in water for 20 min. Maximum swimming led to reactive oxygen species (ROS) generation in skeletal muscle, as indicated by increased thiobarbituric acid reactive species (TBARS) levels (4062.67 ± 1487.10 vs 19,072.48 ± 8738.16 nmol malondialdehyde (MDA)/mg protein, control vs EX1). Exercise also promoted NF-κB activation in soleus muscle. Cytokine secretion following exercise was marked by increased plasma interleukin-6 (IL-6) levels 3 h post-exercise (P < 0.05). Interleukin-10 (IL-10) levels were reduced following exercise and remained reduced 3 h post-exercise (P < 0.05). Plasma levels of other cytokines investigated, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-12 (IL-12), were not altered by exercise. The present findings showed that maximum swimming, as well as other exercise models, led to lipid peroxidation and NF-κB activation in skeletal muscle and increased plasma IL-6 levels. The plasma cytokine response was also marked by reduced IL-10 levels. These results were attributed to exercise type and intensity.

Plasma cytokine response, lipid peroxidation and NF-kB activation in skeletal muscle following maximum progressive swimming.

Our objective was to determine lipid peroxidation and nuclear factor-κB (NF-κB) activation in skeletal muscle and the plasma cytokine profile following maximum progressive swimming. Adult male Swiss mice (N = 15) adapted to the aquatic environment were randomly divided into three groups: immediately after exercise (EX1), 3 h after exercise (EX2) and control. Animals from the exercising groups swam until exhaustion, with an initial workload of 2% of body mass attached to the tail. Control mice did not perform any exercise but were kept immersed in water for 20 min. Maximum swimming led to reactive oxygen species (ROS) generation in skeletal muscle, as indicated by increased thiobarbituric acid reactive species (TBARS) levels (4062.67 ± 1487.10 vs 19,072.48 ± 8738.16 nmol malondialdehyde (MDA)/mg protein, control vs EX1). Exercise also promoted NF-κB activation in soleus muscle. Cytokine secretion following exercise was marked by increased plasma interleukin-6 (IL-6) levels 3 h post-exercise (P < 0.05). Interleukin-10 (IL-10) levels were reduced following exercise and remained reduced 3 h post-exercise (P < 0.05). Plasma levels of other cytokines investigated, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-12 (IL-12), were not altered by exercise. The present findings showed that maximum swimming, as well as other exercise models, led to lipid peroxidation and NF-κB activation in skeletal muscle and increased plasma IL-6 levels. The plasma cytokine response was also marked by reduced IL-10 levels. These results were attributed to exercise type and intensity.

A mitogenic signal triggered at an early stage of vaccinia virus infection: implication of MEK/ERK and protein kinase A in virus multiplication.

Vaccinia virus (VV) triggers a mitogenic signal at an early stage of infection. VV-induced proto-oncogene c-fos mRNA with kinetics paralleling that stimulated by serum. The VV virokine, or vaccinia virus growth factor (VGF), was not crucial for c-fos induction because it was observed upon infection with the virokine-minus mutant VV (VGF(-)). Furthermore, c-fos expression did not require infectious virus particles, as it occurred even with UV-inactivated VV and was equally induced by the different multiplicities of infection, i.e. 1.0, 5.0, and 25.0. c-fos expression was preceded by VV-induced DNA binding activity and was mediated via the cis-acting elements serum response element (SRE), activating protein-1 (AP-1), and cAMP-response element (CRE). VV activated the protein kinases p42MAPK/ERK2 and p44MAPK/ERK1 and the transcription factor ATF1 in a time-dependent manner with kinetics that paralleled those of VV-stimulated DNA-protein complex formation. The mitogenic signal transmission pathways leading to c-fos activation upon VV infection were apparently mediated by the protein kinases MEK, ERK, and PKA. This assumption was based on the findings that: 1) c-fos transcript was down-regulated; 2) the SRE, AP-1, and CRE binding activities were significantly reduced; and 3) the activation of p42MAPK/ERK2, p44MAPK/ERK1, and ATF1 were drastically affected when the viral infections were carried out in the presence of specific protein kinase inhibitor. Moreover, the mutant VV (VGF(-)) was also able to activate ERK1/2. It is noteworthy that virus multiplication was equally affected by the same kinase inhibitors. Taken together, our data provide evidence that the early mitogenic signal triggered upon VV infection relies upon the activation of the protein kinases MEK, ERK, and PKA, which are needed for both signal transduction and virus multiplication.

Suppes predicate for genetics and natural selection.

Patrick Suppes' slogan that "to axiomatize a theory is to present a set-theoretical predicate" was used in the synthetic theory of evolution. The system presented here extends the axiomatics of the evolutionary theory presented by M. Williams to encompass aspects of genetics. Some biological implications of the system are discussed, including the relationship between the Darwinian concept of fitness, as applied to organisms, and the concept of fitness as applied to genotypes, as it is normally used in population genetics. This paper should be viewed as an adjunct to the speculations on the logical-mathematical foundations of biological sciences.

Study on a Brazilian isolate. I. Population structure and random genetic drift.

A number of parameters were evaluated in order to determine the level of isolation of a small Brazilian community existing in partial geographic isolation and thereby evaluate the random genetic drift potential in the population. On a theoretical basis, it is concluded that the probability of genetic drift is low but cannot be excluded. The relatively small proportion of migrants (26%), the limited individual mobility, as given by marital distance (29 +/- 7 km), the mean migrational distance (46 +/- 11 km), the small effective size (122), and the value of the product Neme (26) agree with the possibility of genetic drift in this population. The observed coefficient of inbreeding (0.00239) is lower than that expected (0.0066) for random mating, suggesting some pressures against consanguineous marriage.

Study on a Brazilian isolate. II. Opportunity for selection.

The opportunity for selection, measured by prereproductive mortality and fertility, was calculated for a small and relatively isolated Brazilian population. The total index of selection opportunity (0.53) was low in comparison to those obtained for other isolated populations. The contribution of prereproductive mortality (Im = 0.28) was 40% higher than that of fertility (If = 0.20).