2,3,7,8‑Tetrachlorodibenzo‑p‑dioxin suppresses the growth of human liver cancer HepG2 cells in vitro: Involvement of cell signaling factors.

The aryl hydrocarbon receptor (AHR) is transcriptionally active in the form of a heterodimer with the AHR nuclear translocator, which then binds to the xenobiotic responsive element. AHR was originally discovered via its ligand, the polychlorinated hydrocarbon, 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD). In this study, we investigated whether TCDD regulates the growth of human liver cancer HepG2 cells in vitro. TCDD (0.1‑100 nM) was found to exert suppressive effects on the colony formation and proliferation of HepG2 cells, and stimulatory effects on the death of HepG2 cells when the cells reached subconfluence. The effects of TCDD on the HepG2 cells were abolished by culture with CH223191, an inhibitor of AHR signaling. The effects of TCDD were dependent on the concentration of serum, which contains various signaling factors. The effects of TCDD were not potentiated by culture with tumor necrosis factor‑α, which activates the signaling of nuclear factor‑κB (NF‑κB). The results of western blot analysis revealed that TCDD increased the protein levels of p53, Rb, p21, and regucalcin, which are suppressors of the growth of tumor cells. Moreover, TCDD enhanced the NF‑κB p65, β‑catenin, signal transducer and activator of transcription 3 (STAT3), Ras and Akt levels. Thus, the findings of this study indicate that TCDD may suppress liver cancer cell growth through various signaling pathways, mediated by AHR and its‑related co‑factors. Of note, the effects of TCDD were found to be potentiated by gemcitabine, which induces nuclear DNA damage in cancer cells, suggesting that their combined use may have potential as a suppressor of tumor cell growth

An ultrasonic technique for the measurement of elastic properties of soft surface coatings

The properties of thin layers of materials can be different from those in the bulk form. The response of a coating to any given load and its ability to remain bonded to the substrate will depend on its elastic modulus and Poisson's ratio. In this study a measurement method based on ultrasonic bulk wave reflection was evaluated. As a model system, a thin layer of polyethylene was pressed between two solid steel bodies. The reflection spectra of longitudinal and shear ultrasonic waves were recorded from the coating. The frequencies at which the layer resonates were measured and from this the wave speeds deduced. The Poisson's ratio can be determined from these two wave speeds and if the layer thickness is known the modulus is also available. The tests yielded reasonable values for both. This approach is only suitable if the layer can be made to resonate by the available ultrasonic frequencies; typically this will be the case for thicker coatings (tens of microns). Further, good coupling between the layer material and the steel bodies is necessary so that the interfaces do not themselves act to reflect ultrasound. This is better achieved with a smooth soft coating

Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals.

CXCR4 is a chemokine receptor frequently overexpressed on primary tumor cells. Organs to which these cancers metastasize secrete CXCL12, the unique ligand for CXCR4, which stimulates invasion and metastasis to these sites. Similar to our previous work with the chemoprotective phytochemical, 3,3'-diindolylmethane (DIM), we show here that genistein also downregulates CXCR4 and CXCL12 and subsequently lowers the migratory and invasive potentials of breast and ovarian cancer cells. Moreover, genistein and DIM elicit a significantly greater cumulative effect in lowering CXCR4 and CXCL12 levels than either compound alone. Our data suggest a novel mechanism for the protective effects of phytochemicals against cancer progression and indicate that in combination, these compounds may prove even more efficacious

Aryl Hydrocarbon Receptor-Dependent inductions of omega-3 and omega-6 polyunsaturated fatty acid metabolism act inversely on tumor progression.

The Western diet contains a high ratio of omega-6 (ω6) to omega-3 (ω3) polyunsaturated fatty acids (PUFA). The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), induces CYP1 family enzymes, which can metabolize PUFA to epoxides. Mice fed ω3-rich or ω6-rich diets were treated with TCDD and injected subcutaneously with AHR-competent Hepa1-GFP hepatoma cells or AHR-deficient LLC lung cancer cells. TCDD reduced the growth rates of the resulting tumors in ω3-fed mice and inhibited their metastasis to the liver and/or lung, but had the opposite effects in mice fed ω6 PUFA. These responses were likely attributable to the corresponding PUFA epoxides generated in tumor cells and/or host, since many depended upon co-administration of a soluble epoxide hydrolase (EPHX2) inhibitor in males, and/or were associated with increases in epoxide levels in tumors and sites of metastasis. Equivalent effects occurred in females in the absence of EPHX2 inhibition, probably because this sex expressed reduced levels of EPHX2. The responses elicited by TCDD were associated with effects on tumor vascularity, tumor cell proliferation and/or apoptosis. Thus environmental AHR agonists, and potentially also endogenous, nutritional, and microbiome-derived agonists, may reduce or enhance cancer progression depending on the composition of dietary PUFA, particularly in females

Who participates in local government? Evidence from meeting minutes

Scholars and policymakers have highlighted institutions that enable community participation as a potential buffer against existing political inequalities. Yet these venues may bias policy discussions in favor of an unrepresentative group of individuals. To explore who participates, we compile a novel data set by coding thousands of instances of citizens speaking at planning and zoning board meetings concerning housing development. We match individuals to a voter file to investigate local political participation in housing and development policy. We find that individuals who are older, male, longtime residents, voters in local elections, and homeowners are significantly more likely to participate in these meetings. These individuals overwhelmingly (and to a much greater degree than the general public) oppose new housing construction. These participatory inequalities have important policy implications and may be contributing to rising housing costs.Accepted manuscrip

Modulation of CXCR4, CXCL12, and tumor cell invasion potential in vitro by phytochemicals

CXCR4 is a chemokine receptor frequently overexpressed on primary tumor cells. Organs to which these cancers metastasize secrete CXCL12, the unique ligand for CXCR4, which stimulates invasion and metastasis to these sites. Similar to our previous work with the chemoprotective phytochemical, 3,3 -diindolylmethane (DIM), we show here that genistein also downregulates CXCR4 and CXCL12 and subsequently lowers the migratory and invasive potentials of breast and ovarian cancer cells. Moreover, genistein and DIM elicit a significantly greater cumulative effect in lowering CXCR4 and CXCL12 levels than either compound alone. Our data suggest a novel mechanism for the protective effects of phytochemicals against cancer progression and indicate that in combination, these compounds may prove even more efficacious

Roles of Coactivators in Hypoxic Induction of the Erythropoietin Gene

Hypoxia-inducible expression of the erythropoietin (EPO) gene is mediated principally by hypoxia-inducible factor 2alpha (HIF-2alpha) in Hep3B cells under physiologic conditions. How/whether p300/CBP and the members of p160 coactivator family potentiate hypoxic induction of endogenous EPO and other HIF-2alpha and hypoxia-inducible factor 1alpha (HIF-1alpha) target genes remains unclear.We demonstrate, using chromatin immunoprecipitation (ChIP) analysis, that the histone acetyl transferase (HAT) coactivators p300, SRC-1 and SRC-3 are recruited to the 3' enhancer of the EPO gene upon hypoxic stimulation, and that each associates with the enhancer in a periodic fashion. Hypoxia induced acetylation of the EPO gene 5' promoter at histone 4 and lysine 23 of histone 3. Knocking down SRC-3, but not SRC-1 or SRC-2, using short interfering RNAs (siRNAs), reduced EPO transcriptional activity. Knocking down p300 resulted in dramatic down-regulation of hypoxic stimulation of EPO gene transcription, negated recruitment of RNA polymerase II to the gene's promoter, and eliminated hypoxia-stimulated acetylation at the promoter and recruitments of SRC-1 and SRC-3 to the enhancer. The inhibitory effects of knocking down p300 and the chromatin remodeling coactivator, Brm/Brg-1, on EPO transcription were additive, suggesting that p300 and Brm/Brg-1 act independently. p300 was also required for hypoxia induced transcription of the HIF-1alpha target gene, VEGF, but was dispensable for induction of two other HIF-1alpha target genes, PGK and LDHA. Knocking down CBP, a homolog of p300, augmented hypoxic induction of VEGF, LDHA and PGK. Different HIF target genes also exhibited different requirements for members of the p160 coactivator family.p300 plays a central coactivator role in hypoxic induction of EPO. The coactivators exhibit different specificities for different HIF target genes and each can behave differently in transcriptional regulation of different target genes mediated by the same transcription factor

Mapping hotel brand positioning and competitive landscapes by text-mining user-generated content

YesThis study uncovers hotel brand positioning and competitive landscape mapping by text-mining user-generated content (UGC). Rather than relying on a single dimension of consumer evaluation, the current study detects brand attributes by using both customer preferences as well as perceptual performance to develop meaningful insights. For this, the study combines content analysis and repertory grid analysis (RGA) to answer three key research issues. 111,986 hotel reviews from two biggest Chinese cities are used to explore and visualize the competitive landscape of six selected hotel brands across three hotel categories. Findings from the study will not only advance the existing literature on brand positioning and competitive landscape mapping but also help practitioners in developing brand positioning strategies to fight competitors within and across hotel categories