The epithelial-mesenchymal transition (EMT) is a process through which epithelial cells trans-differentiate and acquire an aggressive mesenchymal phenotype. In tumor cells, EMT is a vital step of tumor progression and metastasis. Amid the increasing interest in tumor EMT, only a few studies focused on the soluble mediators secreted by tumor cells passing through this phenotypic switch. In this review, we focus on the essential role of interleukin-8 (IL-8) signaling for the acquisition and maintenance of tumor EMT via direct and indirect mechanisms. Besides the autocrine loop between IL-8 and tumor cells that have gone through EMT, IL-8 could potentiate adjacent epithelial tumor cells into a mesenchymal phenotype via a paracrine mode. Moreover, understanding the role of IL-8 in EMT will provide insight into the pathogenesis of tumor progression and may facilitate the development of an effective strategy for the prevention and treatment of metastatic cancer.
Resveratrol (trans-3,4V,5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties. Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate. Our data show that resveratrol induces dose-and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase. Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9. Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G 0 /G 1 growth arrest, as determined by flow cytometry. The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis. These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma. [Mol Cancer Ther 2005;4(4):554 -61]
In natural freshwater and sediments, mercuric mercury (Hg(II)) is largely associated with particulate minerals and organics, but it remains unclear under what conditions particulates may become a sink or a source for Hg(II) and whether the particulate-bound Hg(II) is bioavailable for microbial uptake and methylation. In this study, we investigated Hg(II) sorption–desorption characteristics on three organo-coated hematite particulates and a Hg-contaminated natural sediment and evaluated the potential of particulate-bound Hg(II) for microbial methylation. Mercury rapidly sorbed onto particulates, especially the cysteine-coated hematite and sediment, with little desorption observed (0.1–4%). However, the presence of Hg-binding ligands, such as low-molecular-weight thiols and humic acids, resulted in up to 60% of Hg(II) desorption from the Hg-laden hematite particulates but <6% from the sediment. Importantly, the particulate-bound Hg(II) was bioavailable for uptake and methylation by a sulfate-reducing bacterium Desulfovibrio desulfuricans ND132 under anaerobic incubations, and the methylation rate was 4–10 times higher than the desorption rate of Hg(II). These observations suggest direct contacts and interactions between bacterial cells and the particulate-bound Hg(II), resulting in rapid exchange or uptake of Hg(II) by the bacteria. The results highlight the importance of Hg(II) partitioning at particulate–water interfaces and the role of particulates as a significant source of Hg(II) for methylation in the environment.
Complex morphological or functional traits are frequently considered evolutionarily unique and hence useful for taxonomic classification. Flea beetles (Alticinae) are characterized by an extraordinary jumping apparatus in the usually greatly expanded femur of their hind legs that separates them from the related Galerucinae. Here, we examine the evolution of this trait using phylogenetic analysis and a time-calibrated tree from mitochondrial (rrnL and cox1) and nuclear (small subunits and large subunits) genes, as well as morphometrics of femora using elliptic Fourier analysis. The phylogeny strongly supports multiple independent origins of the metafemoral spring and therefore rejects the monophyly of Alticinae, as defined by this trait. Geometric outline analysis of femora shows the great plasticity of this structure and its correlation with the type and diversity of the metafemoral springs. The recognition of convergence in jumping apparatus now resolves the long-standing difficulties of Galerucinae -Alticinae classification, and cautions against the value of trait complexity as a measure of taxonomic significance. The lineage also shows accelerated species diversification rates relative to other leaf beetles, which may be promoted by the same ecological factors that also favour the repeated evolution of jumping as an anti-predation mechanism.
The culture supernatant of Paenibacillus sp. TKU036, a bacterium isolated from Taiwanese soils, showed high antioxidant activity (85%) when cultured in a squid pen powder (SPP)-containing medium at 37 °C for three days. Homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) was isolated and found to be the major antioxidant in the culture supernatant of the SPP-containing medium fermented by Paenibacillus sp. TKU036. Tryptophan was also present in the culture supernatant. The results of high-performance liquid chromatography (HPLC) fingerprinting showed that HGA and tryptophan were produced via fermentation but did not pre-exist in the unfermented SPP-containing medium. Neither HGA nor tryptophan was found in the culture supernatants obtained from the fermentation of nutrient broth or other chitinous material, i.e., medium containing shrimp head powder, by Paenibacillus sp. TKU036. The production of HGA via microorganisms has rarely been reported. In this study, we found that squid pen was a potential carbon and nitrogen source for Paenibacillus sp. Tryptophan (105 mg/L) and HGA (60 mg/L) were recovered from the culture supernatant. The isolated HGA was found to have higher antioxidant activity (IC50 = 6.9 μg/mL) than α-tocopherol (IC50 = 17.6 μg/mL). The anti-inflammatory activity of the isolated HGA (IC50 = 10.14 μg/mL) was lower than that of quercetin (IC50 = 1.14 μg/mL). As a result, squid pen, a fishery processing byproduct, is a valuable material for the production of tryptophan and the antioxidant and anti-inflammatory HGA via microbial conversion.
The wettability of rocks and minerals significantly affects the safety and efficiency of energyrelated subsurface operations. Salinity is an important controlling factor in terms of wettability but has received limited attention. We studied the effects of salinityinduced chemical reactions on biotite's wettability changes under relevant subsurface conditions. Biotite was reacted at 95 °C and 102 atm of CO 2 for 70 h in solutions with salinities of 0, 0.1, 0.5, and 1.0 M NaCl. Then, static and dynamic water contact angles on reacted biotite basal surfaces were measured using a captive drop method. As a result of enhanced biotite dissolution at higher salinities, increased roughness, more negatively charged surfaces, and higher densities of hydroxyl groups on the biotite surfaces made biotite basal surface more hydrophilic. These results provide new information about the interplay of chemical reactions and wettability alterations of minerals, providing a better understanding of CO 2 transport in subsurface environments.
Recent studies have identified HgcAB proteins as being responsible for mercury [Hg(II)] methylation by certain anaerobic microorganisms. However, it remains controversial whether microbes take up Hg(II) passively or actively. Here, we examine the dynamics of concurrent Hg(II) adsorption, uptake, and methylation by both viable and inactivated cells (heat-killed or starved) or spheroplasts of the sulfate-reducing bacterium Desulfovibrio desulfuricans ND132 in laboratory incubations. We show that, without addition of thiols, >60% of the added Hg(II) (25 nM) was taken up passively in 48 h by live and inactivated cells and also by cells treated with the proton gradient uncoupler, carbonylcyanide-3-chlorophenylhydrazone (CCCP). Inactivation abolished Hg(II) methylation, but the cells continued taking up Hg(II), likely through competitive binding or ligand exchange of Hg(II) by intracellular proteins or thiol-containing cellular components. Similarly, treatment with CCCP impaired the ability of spheroplasts to methylate Hg(II) but did not stop Hg(II) uptake. Spheroplasts showed a greater capacity to adsorb Hg(II) than whole cells, and the level of cytoplasmic membrane-bound Hg(II) correlated well with MeHg production, as Hg(II) methylation is associated with cytoplasmic HgcAB. Our results indicate that active metabolism is not required for cellular Hg(II) uptake, thereby providing an improved understanding of Hg(II) bioavailability for methylation.
To better understand how scCO2-saturated brine-mineral interactions can affect safe and efficient geologic CO2 sequestration (GCS), we studied the effects of organic ligands (acetate and oxalate) on biotite dissolution and surface morphological changes. The experimental conditions were chosen to be relevant to GCS sites (95 °C and 102 atm CO2). Quantitative analyses of dissolution differences between biotite edge and basal planes were made. Acetate slightly inhibited biotite dissolution and promoted secondary precipitation. The effect of acetate was mainly pH-induced aqueous acetate speciation and the subsequent surface adsorption. Under the experimental conditions, most of acetate exists as acetic acid and adsorbs to biotite surface Si and Al sites, thereby reducing their release. However, oxalate strongly enhanced biotite dissolution and induced faster and more significant surface morphology changes by forming bidentate mononuclear surface complexes. For the first time, we show that oxalate selectively attacks edge surface sites and enhances biotite dissolution. Thus, oxalate increases the relative reactivity ratio of biotite edge surfaces to basal surfaces, while acetate does not impact this relative reactivity. This study provides new information on reactivity differences at biotite edge and basal planes in the presence of organic ligands, which has implications for safe CO2 storage in organic-rich sites.
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