Association of TNF-308 G>A polymorphism located in tumor necrosis factor a with the risk of developing cervical cancer and results of pap smear

Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF-308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®-probes-based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57-4.83, <0.001) and OR of 7.27 (95%CI: 2.5-20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF-308 G>A located on TNF-a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.     

Signaling Crosstalk of FHIT,p53, and p38 in etoposide-induced apoptosis in MCF-7 cells

Fragile histidine trail (FHIT) is a tumor suppressor in response to DNA damage which has been deleted in various tumors. However, the signaling mechanisms and interactions of FHIT with regard to apoptotic proteins including p53 and p38 in the DNA damage-induced apoptosis are not well described. In the present study, we used etoposide-induced DNA damage in MCF-7 as a model to address these crosstalks. The time course study showed that the expression of FHIT, p53, and p38MAPK started after 1 hour following etoposide treatment. FHIT overexpression led to increase p53 expression, p38 activation, and augmented apoptosis following etoposide-induced DNA damage compared to wild-type cells. However, FHIT knockdown blocked p53 expression, delayed p38 activation, and completely inhibited etoposide-induced apoptosis. Inhibition of p38 activity prevented induction of p53, FHIT, and apoptosis in this model. Thus, activation of p38 upon etoposide treatment leads to increase in FHIT and p53 expression. In p53 knockdown MCF-7, the FHIT induction was hampered but p38 activation was induced in lower doses of etoposide. In p53 knockdown cells, inhibition of p38 induced FHIT expression and apoptosis. Our data demonstrated that the exposure of MCF-7 cells to etoposide increases apoptosis through a mechanism involving the activation of the p38-FHIT-p53 pathway. Moreover, our findings suggest signaling interaction for these pathways may represent a promising therapy for breast cancer.     

Breeding and selection of Buxus for resistance to Calonectria pseudonaviculata

Box blight is a widespread disease of Buxus caused by the pathogen Calonectria pseudonaviculata. It is responsible for significant losses in nurseries, gardens and wild boxwood populations. Our goal was to maximize the efficiency of a breeding programme towards increased disease resistance. The use of artificial inoculation of young F1 seedlings with C. pseudonaviculata spores under greenhouse conditions appeared to be a reliable tool for early selection of interesting prebreeding material. Overall, the four hybrid populations screened showed a segregating behaviour between their parents when determining the percentage of diseased leaves and lesion diameter. Genotypes were also found with an increased tolerance as compared to the parental species. Approximately 50% of the seedlings had the same score for both parameters after artificial inoculation in the greenhouse and in the field. Of the seedlings that showed severe symptoms in the greenhouse, <15% showed no disease symptoms in the field. Therefore, for larger breeding programmes, we propose a two‐step selection procedure: first artificial inoculation at seedling level to eliminate all genotypes with severe symptoms and then evaluation of the remaining seedlings in the field. Using this strategy, we were able to select several genotypes in our four hybrid populations with improved resistance to C. pseudonaviculata.     

Interaction of CR6 (GADD45gamma ) with proliferating cell nuclear antigen impedes negative growth control

GADD45, MyD118, and CR6 (also termed GADD45alpha, beta, and gamma) comprise a family of genes that encode for related proteins playing important roles in negative growth control, including growth suppression. Data accumulated suggest that MyD118/GADD45/CR6 serve similar but not identical functions along different apoptotic and growth suppressive pathways. It is also apparent that individual members of the MyD118/GADD45/CR6 family are differentially induced by a variety of genetic and environmental stress agents. The MyD118, CR6, and GADD45 proteins were shown to predominantly localize within the cell nucleus. Recently, we have shown that both MyD118 and GADD45 interact with proliferating cell nuclear antigen (PCNA), a protein that plays a central role in DNA replication, DNA repair, and cell cycle progression, as well as with the universal cyclin-dependent kinase inhibitor p21. In this work we show that also CR6 interacts with PCNA and p21. Moreover, it is shown that CR6 interacts with PCNA via a domain that also mediates interaction of both GADD45 and MyD118 with PCNA. Importantly, evidence has been obtained that interaction of CR6 with PCNA impedes the function of this protein in negative growth control, similar to observations reported for MyD118 and GADD45.     

Inhibitory action of a new lectin from Xerocomus chrysenteron on cell-substrate adhesion

Lectins are carbohydrate-binding proteins which potentially link to cell surface glycoconjugates and affect cell proliferation. We investigated the effect of a new lectin from the mushroom Xerocomus chrysenteron (XCL) on cell proliferation using adherent and suspension cell lines. XCL caused a dose-dependent inhibition of proliferation of the adherent cell lines NIH-3T3 and HeLa. Several experiments suggest that disruption of cell-substrate adhesion is the main factor affecting cell growth inhibition. (i) No antiproliferative effect was observed on the SF9 cell line, which does not require to be attached to grow. (ii) XCL was shown to affect the adherence of cells following their suspension by trypsin treatment. (iii) XCL was localized on the cell surface where it would act as a coating agent. (iv) XCL induced morphological changes from well spread to rounded cells and disrupted the actin cytoskeleton. By contrast, flow cytometric analysis showed that XCL does not interfere with the cell cycle, and does not induce apoptosis.     

Vascular biomaterials: from biomedical engineering to tissue engineering

Biomaterials are already widely used in medical sciences. The field of biomaterials began to shift to produce materials able to stimulate specific cellular responses at the molecular level. The combined efforts of cell biologists, engineers, materials scientists, mathematicians, geneticists, and clinicians are now used in tissue engineering to restore, maintain, or improve tissue functions or organs. This rapidly expanding approach combines the fields of material sciences and cell biology for the molecular design of polymeric scaffolds with appropriate 3D configuration and biological responses. Future developments for new blood vessels will require improvements in technology of materials and biotechnology together with the increased knowledge of the interactions between materials, blood, and living tissues. Biomaterials represent a crucial mainstay for all these studies.     

Root anchorage of inner and edge trees in stands of Maritime pine (<Emphasis Type="Italic">Pinus pinaster</Emphasis> Ait.) growing in different podzolic soil conditions

Static winching tests were carried out in order to determine the mechanical resistance of Maritime pine to overturning. The tested stands were selected according to podzolic soil conditions: wet Lande, characterised by a shallow ground water table and a hard pan horizon, and dry Lande, with a deeper ground water table and a hard pan absent or broken up. As this soil horizon limits the vertical growth of tree roots, anchorage resistance was investigated with regards to the presence or absence of a hard pan underneath each tree. To determine if mechanical behaviour differed within a stand, trees from inside the stand and edge trees at the border exposed to prevailing winds were also tested. The critical turning moment (TM_crit,total) at the base of the stem was positively related to the variable (H × DBH²) (H, total tree height; DBH, tree diameter). Linear regression analyses between TM_crit,total and (H × DBH²) showed that the presence of a hard pan had no significant effect on anchorage resistance in uprooted trees. Stem failure occurred for 82% of trees on dry Lande when (H × DBH²) < 1 m³. Moreover, stem failure type on dry Lande indicated that trees were better anchored. On soil with a hard pan, edge trees were found to be 20% more resistant to overturning than inner trees. Edge trees differed from inner trees in that the soil-root plate was two times larger and also possessed a larger surface area on the windward side.