Phytochemicals Induce Apoptosis By Modulation Of Nitric Oxide Signaling Pathway In Cervical Cancer Cells

OBJECTIVE: Nitric Oxide (NO) is produced by NO synthases (NOS) and is a key signaling molecule that regulates tumorigenesis, both aiding and alleviating it. Elevated NO levels are cytotoxic to cancer cells, making NOS an important target for cancer treatment. In the present study, the modulatory effects of the phytochemicals, quercetin, sulforaphane, genistein, and epigallocatechin-3-gallate on NO pathway and apoptosis were shown in HeLa cervical cancer cells. MATERIALS AND METHODS: Fluorescent microscopy and flow cytometry were used to assess apoptosis. A Griess assay was used to quantitatively measure NO, quantitative PCR array was used to assess the expression levels of genes involved in the NO signaling pathway, and immunocytochemistry was used to determine NOS protein expression. The functional association among the modulated genes was evaluated using network biology analysis. gene set enrichment, and KEGG pathway analysis. RESULTS: Treatment with the phytochemicals elevated NO levels in HeLa cells and modulated various genes involved in nitric oxide biosynthesis, superoxide metabolism. and oxidative stress, including NOS1, NOS2, NOS3, ALOX12, and SOD2, with a concomitant increase in NOS2 and NOS3 protein expression levels: also. the phytochemicals were found to induce apoptosis. CONCLUSIONS: These results suggest that the phytochemical-induced cell death is partially attributed to the activation of the NO pathway and upregulation of pro-oxidant ROS generators. Further experimental studies are required to explore this mechanistic association of NO signaling pathway activation and induction of apoptosis in other types of cancer

Constraining the magnitude of the Chiral Magnetic Effect with Event Shape Engineering in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76$ TeV

In ultrarelativistic heavy-ion collisions, the event-by-event variation of the elliptic flow $v_2$ reflects fluctuations in the shape of the initial state of the system. This allows to select events with the same centrality but different initial geometry. This selection technique, Event Shape Engineering, has been used in the analysis of charge-dependent two- and three-particle correlations in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}} =2.76$ TeV. The two-particle correlator $\langle \cos(\varphi_\alpha - \varphi_\beta) \rangle$, calculated for different combinations of charges $\alpha$ and $\beta$, is almost independent of $v_2$ (for a given centrality), while the three-particle correlator $\langle \cos(\varphi_\alpha + \varphi_\beta - 2\Psi_2) \rangle$ scales almost linearly both with the event $v_2$ and charged-particle pseudorapidity density. The charge dependence of the three-particle correlator is often interpreted as evidence for the Chiral Magnetic Effect (CME), a parity violating effect of the strong interaction. However, its measured dependence on $v_2$ points to a large non-CME contribution to the correlator. Comparing the results with Monte Carlo calculations including a magnetic field due to the spectators, the upper limit of the CME signal contribution to the three-particle correlator in the 10-50% centrality interval is found to be 26-33% at 95% confidence level.Comment: 20 pages, 6 captioned figures, 1 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/382

Gendered immobility: influence of social roles and local context on mobility decisions in Pakistan

This paper examines the instances of one-day immobility in Pakistan and reports its socio-demographic determinants using the nationally representative dataset of the 2007 Pakistan Time Use Survey. Of 37,830 time diary respondents, nearly 30% did not report travel during the diary day. Homemakers and those out of the workforce were more likely to be immobile than employed or student respondents. Immobility rates were very high among women (55%) as compared to men (4%). Among women, those between 20 and 34 years of age, married, with children, having better education, dependent on other household members and those living in higher income households were more likely to be immobile. The excessive gender nature of immobility seems to be triggered by a gender-based sociocultural environment, which restricts female mobility due to family honor concerns. Other than this, those living in the provinces of Sindh and Khyber Pakhtunkhwa or in urban areas were more likely to be immobile than those living in Punjab and Sindh provinces or in rural areas. The significant geographic effect at broader spatial scale is caused by the demographic structure as well as due to differences in the social and cultural context of these areas. Finally, questions regarding the measurement of immobility and the potential implications of increased female immobility are discussed