Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: The role of p38 MAPK and ROS

Due to narrow therapeutic window of cancer therapeutic agents and the development of resistance against these agents, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro and in vivo. Cell responses after TQ treatment were assessed by using different assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining and Western blot. The antitumor effect was studied by breast tumor xenograft mouse model, and the tumor tissues were examined by histology and immunohistochemistry. The level of antioxidant enzymes/molecules in mouse liver tissues was measured by commercial kits. Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells. These inductions were found to be responsible for TQ’s anti-proliferative and pro-apoptotic effects. Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice versa. TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin. TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors. TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues. Overall, our results demonstrated that the antiproliferative and pro-apoptotic effects of TQ in breast cancer are mediated through p38 phosphorylation via ROS generation

Reaching the last child: Evidence from Young Lives India

This summative country report draws upon fifteen years of evidence captured by the Young Lives study in India. It provides an overview and synthesis of a much more detailed evidence base, much of which can be found on the project website. Some new analysis has been completed for this report to bring it right up to date. Many of the findings are drawn from journal articles and working papers which have been subject to separate review processes. Young Lives ran parallel to the Millennium Development Goals (MDGs) and utilised mixed methods consisting of surveys, in-depth interviews and focus groups to improve understanding of the causes and consequences of childhood poverty, and to examine how policies affect children’s well-being. Drawing upon significant information gathered about children’s experiences as they transition from early childhood to adolescence and early adulthood, this report attempts to capture and highlight key findings from various papers, policy briefs and journal articles written over the period since 2002. The research has been guided by three intersecting lines of enquiry: (1) an analysis of the factors shaping children’s growth and development over the course of their lives; (2) development of the understanding that risk and deprivation are concentrated in particular social groups and localities, with dramatic disparities in children’s outcomes, leading to questions about what these inequalities mean for children; (3) an examination of the changing influences in children’s lives, including the risks to which they are exposed and the support they enjoy. This has been achieved specifically by comparisons between the two cohorts of children that the Young Lives project followed, and more generally by linking data on the children and the households they live in to the political-economic, socio-cultural and institutional context

Solid-state drawing of post-consumer isotactic poly(propylene): effect of melt filtration and carbon black on structural and mechanical properties

\u3cp\u3ePost-consumer plastic waste obtained via mechanical recycling is usually applied in thick-walled products, because of the low mechanical strength due to the presence of contaminants. In fact, sorted post-consumer isotactic poly(propylene) (i-PP) can be considered as a blend of 95% i-PP and 5% poly(ethylene), with traces of poly(ethylene terephthalate) (PET). By applying a treatment such as solid-state drawing (SSD) after melt extrusion, the polymer chains can be oriented in one direction, thereby improving the stiffness and tensile strength. In this research, molecular processes such as crystal break-up and chain orientation of these complex blends were monitored as a function of draw ratio. The melt filter mesh size - used to exclude rigid PET particles - and the addition of carbon black (CB) - often added for coloration in the recycling industry - were varied to investigate their influence on the SSD process. This research shows that despite the blend complexity, the molecular processes during SSD compare to virgin i-PP and that similar draw ratios can be obtained (λ\u3csub\u3emax\u3c/sub\u3e = 20), albeit at reduced stiffness and strength as a result of the foreign polymers present in post-consumer i-PP. It is observed that the process stability improves with decreasing mesh size and that higher draw ratios can be obtained. The addition of carbon black, which resides in the dispersed PE phase, also stabilizes the SSD process. Compared to isotropic post-consumer i-PP, the stiffness can be improved by a factor 10 to over 11 GPa, while the tensile strength can be improved by a factor 15-385 MPa, which is approx. 70% of the maximum tensile strength achieved for virgin i-PP.\u3c/p\u3