Virtual screening and assessment of anticancer potential of selenium-based compounds against HL-60 and MCF7 cells.

Aim: Selenium-based compounds have antitumor potential. We used a ligand-based virtual screening analysis to identify selenoglycolicamides with potential antitumor activity. Results & Conclusion: Compounds 3, 6, 7 and 8 were selected for in vitro cytotoxicity tests against various cell lines, according to spectrophotometry results. Compound 3 presented the best cytotoxicity results against a promyelocytic leukemia line (HL-60) and was able to induce cell death at a frequency similar to that observed for doxorubicin. The docking study showed that compound 3 has good interaction energies with the targets caspase-3, 7 and 8, which are components of the apoptotic pathway. These results suggested that selenium has significant pharmacological potential for the selective targeting of tumor cells, inducing molecular and cellular events that culminate in tumor cell death.

Latex protein extracts from Calotropis procera with immunomodulatory properties protect against experimental infections with Listeria monocytogenes.

BACKGROUND: The latex from the medicinal plant Calotropis procera is often used in folk medicine against infectious and inflammatory diseases. PURPOSE: In this study, we investigate a protein fraction with immunomodulatory properties, named LPPI, against experimental infections, in vitro and in vivo, with a virulent strain of Listeria monocytogenes. STUDY DESIGN: LPPI was exposed to cultured macrophages or Swiss mice and then challenged with L. monocytogenes. METHODS: Peritoneal macrophages were obtained from Swiss mice, and cultured in 96-well microplates. Soluble latex proteins (LP) were subjected to fractionation by ion-exchange chromatography. The major peak (LPPI) was added into wells at 10 or 100µg/ml. Albumin (100µg/ml) was used for comparison between protein treatments. After incubation for 1h at 5% CO2/ 37°C, the supernatant was discarded and 0.2ml of L. monocytogenes overnight culture was added in the wells. Following 4h and 24h infection, the cytokine mRNA expression was evaluated as well as the number of intracellular colony forming units. Swiss mice (n=16) were injected intraperitoneally (i.p.) with LPPI (5 and 10mg/kg) while the control mice received albumin (10mg/kg) or LP (10mg/kg). After 24h, all animal groups were challenged with L. monocytogenes (10(6) CFU/ ml), also by i.p. route. RESULTS: LPPI was not toxic to uninfected macrophages (pMØ) and significantly increased mRNA expression of TNF-α, IL-6, IL-1ß and iNOS. Following infection, cell viability was reduced by 50% in albumin-treated pMØ (control); but only 17% in pMØ treated with LPPI at 100µg/ml. In this case, LPPI increased expression of TNF-α and IL-6 whereas the number of bacterial colony-forming units was reduced 100-fold in comparison to control groups. Swiss mice pretreated with LPPI showed dose-dependent survival rates that reached 80%, while mice that received albumin died 1-3 days after infection. After 24h infection, leukocyte migration to the infectious foci was high in LPPI-treated mice whereas the number of viable bacteria in the peritoneal fluid, liver and bloodstream were significantly reduced. CONCLUSION: We conclude that LPPI present immunomodulatory properties that are beneficial for prevention of systemic bacterial infections caused by the intracellular bacteria L. monocytogenes.

Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal hens by altering the PG and oestrogen pathways in a dose-dependent manner.

The objective of the present study was to find the optimum dose of flaxseed that would decrease PG and alter oestrogen pathway endpoints implicated in ovarian cancer. In the study, four groups of fifty 1.5-year-old chickens were fed different amounts of flaxseed (0, 5, 10 or 15% of their total diet) for 4 months and were then killed to collect blood and tissues. Levels of flaxseed lignan metabolites, Enterolactone (EL) and Enterodiol (ED) were measured in the serum, liver and ovaries by liquid chromatography-MS/MS, and n-3 and n-6 fatty acid (FA) levels were measured by GC. The effects of the varied flaxseed doses were assessed by measuring levels of PGE2 and oestrogen metabolites (16-hydroxyestrone (16-OHE1) and 2-hydroxyestrone (2-OHE1)) as well as by analysing the expression of the oestradiol metabolising enzymes CYP3A4 (cytochrome p450, family 3, subfamily A, polypeptide 4), CYP1B1 (cytochrome p450, family 1, subfamily B, polypeptide 1) and CYP1A1 (cytochrome p450, family 1, subfamily A, polypeptide 1) and that of oestrogen receptor α (ERα) in the ovaries. The ratio of n-3:n-FA increased with an increase in flaxseed supplementation and corresponded to a dose-dependent decrease in cyclo-oxygenase-2 protein and PGE2 levels. EL and ED increased in the serum, liver and ovaries with increased concentrations of flaxseed. Flaxseed decreased the expression of ERα in the ovaries. The ratio of 2-OHE1:16-OHE1 in the serum increased significantly in the 15% flaxseed diet, and there was a corresponding increase in CYP1A1 in the liver and decrease in CYP3A4 in the ovaries. CYP1B1 mRNA also decreased with flaxseed diet in the ovaries. The 15% flaxseed-supplemented diet significantly decreased inflammatory PGE2, ERα, CYP3A4, CYP1B1 and 16-OHE1, but it increased CYP1A1 and 2-OHE1, which thus reduced the inflammatory and pro-carcinogenic micro-environment of the ovaries.

Avaliação periodontal clínica e microbiológica em mães de prematuros: estudo caso-controle / Clinical and microbiological periodontal evaluation in mothers of preterm birth: case control study

Objetivo: Determinar os parâmetros clínicos periodontais e a frequência de bactérias periodontopatogênicas no biofilme subgengival de mães de prematuros comparativamente às mães de bebês a termo. Método: Foi realizado um estudo caso-controle envolvendo 40 mulheres. Foram incluídas 20 mães de prematuros no grupo caso, enquanto no grupo controle foram incluídas 20 mães de bebês a termo. Em até 48 horas após o parto, as participantes do estudo foram submetidas a uma entrevista, contendo dados de identificação, sociodemográficos, hábitos de vida, história gestacional atual e pregressa, e um exame periodontal, onde foram coletados dados de profundidade de sondagem, sangramento à sondagem, Índice de placa e perda de inserção periodontal. Na análise microbiológica do biofilme subgengival foram analisadas as bactérias Tannerella forsythia, Treponema denticola, Porphyromonas gingivalis e Aggregatibacter actinomycetemcomitans, realizada através da técnica da PCR convencional. Resultados: As médias da perda de inserção clínica e sangramento à sondagem mostraram-se significativamente superiores nas mães de bebês prematuros (p=0,049; p= 0,031, respectivamente). A Porphyromonas gingivalis mostrou-se significativamente mais frequente no grupo caso (p= 0,044). Conclusão: Sugere-se que a inflamação e perda de inserção periodontal bem como a presença da Porphyromonas gingivalis no biofilme subgengival possam estar associados à prematuridade.

Objective: The aim of this research was to determine periodontopathogens samples frequency in subgingival biofilm of pre-term delivery newborn mothers in comparison to women who experienced full-term delivery. Method: Twenty pre-term delivery newborn mothers and 20 women with full-term pregnancy were included in groups case and control, respectively. Up to forty-eight hours after the delivery, the patients were submitted to an interview, including identification, actual and late pregnancy history , life habits and a periodontal examination, which included probing depth, bleeding on probing, plaque index and clinical attachment loss. Microbiological analysis of the subgingival biofilm was carried out by conventional PCR technique to evaluate Tannerella forsythia, Treponema denticola, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Results: Clinical attachment loss and bleeding on probing means were significantly higher at case group (p=0.049; p = 0.031, respectively). Porphyromonas gingivalis was most frequent at the same group, with a significant difference (p=0.044). Periodontal disease was not associated to pre-term delivery. Conclusion: It can be suggested that periodontal tissues inflammation and the clinical attachment loss, as well as Porphyromonas gingivalis presence in subgingival biofilm may be associated to prematurity.