Effect of the aqueous extract of Ginkgo biloba L., Ginkgoaceae, in induced osteoporosis in Wistar rats

The objective of this study was to investigate the effect of a 20 day treatment with extract of Ginkgo biloba (EGb) in glucocorticoid-induced-osteoporosis. 36 rats were divided into six groups (n=6): control, osteoporosis, positive control, EGb1 (14 mg EGb/kg/day), EGb2 (28 mg EGb/kg/day) and EGb3 (56 mg EGb/kg/day). Treatments were conducted for twenty days, after osteoporosis was induced. Following euthanasia the femur and mandible of all animals were removed. The left mandible was radiographed to evaluate the cortical and the periodontal bone support (PBS). The histomorphometric analysis was performed on the right mandible and the right femur. The control group was compared with the osteoporosis group (Student's t-test). The other groups were analyzed through ANOVA test followed by Dunnett post-hoc test. There was a significantly reduction in the mesial PBS, in the percentage of the alveolar bone (PAB) of the mandible and percentage of the trabecular bone (PTB) of the femur in the osteoporosis group. There was an increase in the mesial PBS in the positive control group, EGb2 and EGb3. The PAB of the mandible and the PTB of the femur increased in the EGb2 and EGb3 groups. The EGb in the 28 mg/kg and 56 mg/kg doses were effective to increase the mesial PBS, the PAB of the mandible and the PTB of the femur.Este trabalho investigou os efeitos do tratamento por vinte dias com extrato de Ginkgo biloba (EGb) na osteoporose induzida por glicocorticóides. Foram utilizadas 36 ratas divididas em seis grupos (n=6): Controle, osteoporose, controle positivo, EGb1 (14 mg EGb/mg/kg/dia), EGb2 (28 mg EGb/kg/dia) e EGb3 (56 mg EGb/kg/dia). Os tratamentos foram realizados por vinte dias, após a indução da osteoporose. Após a eutanásia foram removidos o fêmur e a mandíbula de todos os animais. A mandíbula esquerda foi radiografada digitalmente para avaliação da cortical e do suporte ósseo periodontal (SOP). A análise histomorfométrica foi realizada no fêmur e mandíbula direitos. O grupo controle foi comparado ao grupo osteoporose (Teste t de Student) e os demais grupos foram submetidos a ANOVA, seguido do teste post-hoc de Dunnett. Houve redução significava do SOP mesial, percentual ósseo alveolar (POA) mandibular, percentual ósseo trabecular (POT) do fêmur no grupo osteoporose. Houve aumento do SOP mesial no grupo controle positivo, EGb2 e EGb3. O POA da mandíbula e o POT do fêmur aumentaram nos grupos EGb2 e EGb3. O EGb nas doses de 28 mg/kg e 56 mg/kg recuperou de forma significativa o SOP mesial, o POA da mandíbula e o POT do fêmur

Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line

Glioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of Hedychium coronarium, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer.This research was funded by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/06636–7 and 2016/06137–6), financiadora de Estudos e Projetos FINEP (MCTI/FINEP/MS/SCTIE/DECIT–01/2013–FPXII–BIOPLAT)

The impact of polymorphic variations in the 5p15, 6p12, 6p21 and 15q25 loci on the risk and prognosis of Portuguese patients with non-small cell lung cancer

Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. MATERIALS AND METHODS: Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF -460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p?=?0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p?=?0.042; rs3025010 (VEGF intron 5 C/T), p?=?0.047; rs401681 C/T at 5p15, p?=?0.046; and rs31489 C/A at 5p15, p?=?0.029. CONCLUSIONS: Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well.This project was supported by Programa Doutoral em Medicina e Oncologia Molecular, University of Porto, Porto, Portugal and University of Minho, Braga, Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Bacterial cellulose-lactoferrin as an antimicrobial edible packaging

Bacterial cellulose (BC) films from two distinct sources (obtained by static culture with Gluconacetobacter xylinus ATCC 53582 (BC1) and from a commercial source (BC2)) were modified by bovine lactoferrin (bLF) adsorption. The functionalized films (BC+bLF) were assessed as edible antimicrobial packaging, for use in direct contact with highly perishable foods, specifically fresh sausage as a model of meat products. BC+bLF films and sausage casings were characterized regarding their water vapour permeability (WVP), mechanical properties, and bactericidal efficiency against two food pathogens, Escherichia coli and Staphylococcus aureus. Considering their edibility, an in vitro gastrointestinal tract model was used to study the changes occurring in the BC films during passage through the gastrointestinal tract. Moreover, the cytotoxicity of the BC films against 3T3 mouse embryo fibroblasts was evaluated. BC1 and BC2 showed equivalent density, WVP and maximum tensile strength. The percentage of bactericidal efficiency of BC1 and BC2 with adsorbed bLF (BC1+bLF and BC2+bLF, respectively) in the standalone films and in inoculated fresh sausages, was similar against E. coli (mean reduction 69 % in the films per se versus 94 % in the sausages) and S. aureus (mean reduction 97 % in the films per se versus 36 % in the case sausages). Moreover, the BC1+bLF and BC2+bLF films significantly hindered the specific growth rate of both bacteria. Finally, no relevant cytotoxicity against 3T3 fibroblasts was found for the films before and after the simulated digestion. BC films with adsorbed bLF may constitute an approach in the development of bio-based edible antimicrobial packaging systems.The authors would like to acknowledge Portuguese Foundation for Science and Technology (Fundação para a Ciência e Tecnologia) for the research grants: Jorge Padrão SFRH/BD/64901/2009, Sara Gonçalves SFRH/BD/63578/2009, João Pedro Silva SFRH/BPD/ 64958/2009, Ana Cristina Pinheiro SFRH/BPD/101181/2014. V. Sencadas thanks support from the COST Action MP1206: “Electrospun nano-fibres for bio inspired composite materials and innovative industrial applications” and MP1301: “New Generation Biomimetic and Customized Implants for Bone Engineering”. The authors would also like to thank the co-funded by the Programa Operacional Regional do Norte (ON.2 e O Novo Norte), QREN, FEDER Projects “BioHealth e Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124- FEDER-000027; “BioInd e Biotechnology and Bioengineering for improved Industrial and Agro-Food processes”, REF. NORTE-07- 0124-FEDER-000028; Strategic Project PEST-C/FIS/UI607/2014; Matepro eOptimizing Materials and Processes”, ref. NORTE-07- 0124-FEDER-000037; Strategic Project PEst-OE/EQB/LA0023/2013 and project ref. RECI/BBB-EBI/0179/2012 (project number FCOMP- 01-0124-FEDER-027462). Finally, the authors thank the Fundação para a Ciência e Tecnologia for the strategic funding from the UID/ BIO/04469/2013 unit