Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.
Telomeres are specialised nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. The loss of the ends of the chromosomes due to these un-rejoined double strand breaks (DSBs) may not be lethal to the cell, but may instead result in the loss of functional telomeres, chromosome fusions and initiation of breakage/fusion/bridge cycle-induced chromosome instability. The telomeres also participate in the process of DNA repair, as evidenced by 'de novo' synthesis of telomere repeats at DSBs and by the capacity of telomeres to binding the essential components of the DNA repair machinery. Based on the observation that high-LET radiations efficiently induce chromosome aberrations, it was tested whether protons were able to affect telomere structure. Human primary fibroblasts (HFFF2) and mouse embryonic fibroblasts (MEFs) were irradiated with 4 Gy of 3 MeV protons at the radiobiology facility of the INFN-LNL. Experiments with X rays were also carried out. Cells were fixed after either 24 h or 15 d from treatment. A difference in average telomere length, measured by quantitative fluorescence in situ hybridisation (Q-FISH), between X rays and protons treatment was observed. X rays are able to modify telomere length in HFFF2 harvested at a later time. On the other hand, 3 MeV low-energy protons induced, both in HFFF2 and in MEFs, a significant increase in telomere length at short as well as at long harvesting time periods from treatment. These results seem to indicate that lesions characterised by different complexity, as those expected after low-energy protons and those induced by damage similar to that induced by sparsely ionising radiation, are able to modulate telomere elongation at different time periods.
Histone H3 methylation on K9 and/or K27 depends on histone lysine methyltransferases (KMTs). EZH2, one of the components of the PRC2 complex, catalyzes the trimethylation of histone H3K27, which is associated with transcriptional repression and tumor development. H3K9me3 mediated gene silencing may result from other KDMs such as G9a/GLP, SUV39H1-2, SETDB1, CCLD8 and RIZ1. Their disturbance leads to defective cell mitosis. It is therefore desirable to find small molecules that are able to decrease H3K9 and K27 tagging to reinitiate gene transcription. Most KDM inhibitors are still based on SAM co-factor competition/modulation. Herein, functional screening of a diversity library proved to be a useful tool for finding new specific KDM inhibitors; the use of SAM-based pharmacophoric models facilitated the understanding of their possible mechanism of action
cases of this strategy being adopted to overcome contingent issues. 18,19 In addition, the long-term benefits that may be derived from BITA use are still unproven. 15 Therefore, we reviewed pooled results from 3 large series of patients who underwent BITA grafting concomitant with other cardiac operations at 3 European centers with extensive experience in BITA use. The aims of this retrospective study were to describe the immediate and long-term outcomes of these patients, and to identify independent T he use of bilateral internal thoracic artery (BITA) for multiple coronary artery bypass grafting (CABG) in addition to other cardiac operations (combined CABG) is mostly regarded as a risky strategy. The increased length of surgery, as well as the increased risk of bleeding and sternal complications from BITA harvest 1-15 could outweigh the potential benefits of reduced manipulation of the ascending aorta, either natural or prosthetic. 6,7,10,16,17 Consequently, there are no large studies exploring the outcomes of surgery that combines use of BITA with procedures on cardiac valves, the left ventricle, and/or thoracic aorta. The only available evidence stems from anecdotal Editorial p 2416
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