Induction of the Cytochrome P450 Gene CYP26 during Mucous Cell Differentiation of Normal Human Tracheobronchial Epithelial Cells

ABSTRACT In this study, the expression of CYP26 is examined in relation to retinoid-induced mucosecretory differentiation in human tracheobronchial epithelial (HTBE) cells and compared with that in human lung carcinoma cell lines. In HTBE cells, retinoic acid (RA) inhibits squamous differentiation and induces mucous cell differentiation as indicated by the suppression of transglutaminase I and increased expression of the mucin gene MUC2. The latter is accompanied by increased expression of CYP26 mRNA. RA is required but not sufficient to induce RAR␤, CYP26, and MUC2 mRNA because induction is only observed in confluent but not in logarithmic cultures, suggesting that additional factors are critical in their regulation. CYP26 mRNA can be induced by the RAR-selective retinoid 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)-benzoic acid (TTAB) but not by the RXR-selective retinoid SR11217 or the antiactivator-protein 1-selective retinoid SR11302. RAR␣-, ␤-, and ␥-selective retinoids are able to induce CYP26; this induction is inhibited by the RAR␣-selective antagonist Ro41-5253. TTAB is able to induce CYP26 mRNA expression in only a few of the lung carcinoma cell lines tested. The lack of CYP26 induction in many carcinoma cell lines may relate to previously reported defects in the retinoid-signaling pathway. The induction of CYP26 correlated with increased metabolism of RA into 18-hydroxy-, 4-oxo-, and 4-hydroxy-RA. The latter metabolite was shown to be able to induce MUC2 and MUC5AC expression in HTBE cells. Our results demonstrate that in normal HTBE cells, CYP26 expression is closely associated with mucous cell differentiation and that many lung carcinoma cells exhibit increased RA metabolism and a defective regulation of CYP26

Southern Hemisphere mid- and high-latitudinal AOD, CO, NO2, and HCHO: spatiotemporal patterns revealed by satellite observations

To assess air pollution emitted in Southern Hemisphere mid-latitudes and transported to Antarctica, we investigate the climatological mean and temporal trends in aerosol optical depth (AOD), carbon monoxide (CO), nitrogen dioxide (NO2), and formaldehyde (HCHO) columns using satellite observations. Generally, all these measurements exhibit sharp peaks over and near the three nearby inhabited continents: South America, Africa, and Australia. This pattern indicates the large emission effect of anthropogenic activities and biomass burning processes. High AOD is also found over the Southern Atlantic Ocean, probably because of the sea salt production driven by strong winds. Since the pristine Antarctic atmosphere can be polluted by transport of air pollutants from the mid-latitudes, we analyze the 10-day back trajectories that arrive at Antarctic ground stations in consideration of the spatial distribution of mid-latitudinal AOD, CO, NO2, and HCHO. We find that the influence of mid-latitudinal emission differs across Antarctic regions: western Antarctic regions show relatively more back trajectories from the mid-latitudes, while the eastern Antarctic regions do not show large intrusions of mid-latitudinal air masses. Finally, we estimate the long-term trends in AOD, CO, NO2, and HCHO during the past decade (2005-2016). While CO shows a significant negative trend, the others show overall positive trends. Seasonal and regional differences in trends are also discussed

Polyneuropathy Associated with IgA Paraproteinemia and Amyloidosis: A Case Report and Literature Review

Paraproteinemia potentially causes peripheral neuropathy via an unknown underlying pathogenetic mechanism. We report a case of pathologically proven amyloid neuropathy with AL amyloidosis with an IgA kappa light chain, which was initially diagnosed as neuropathy associated with monoclonal gammopathy of undetermined significance. This case indicates that in cases of neuropathy with paraproteinemia, the other potential causes should be excluded by appropriate means, especially pathological evaluations

Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma

Background/Aims: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1–cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms. Methods: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays were performed to determine the link between PAK1 and CREB. NSCLC xenograft models were used to study oncogenic function of PAK1 in vivo. Results: We observed that PAK1 and CREB expression levels were significantly elevated in human squamous NSCLC-tissue specimens, compared with those in adjacent normal bronchial or bronchiolar epithelial-tissue specimens, as well as their phosphorylated forms, based on western blotting. We showed in vitro that PAK1 knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133, based on western blotting. In addition, PAK1 interacted with CREB in co-immunoprecipitation assays. Additionally, our in vitro findings detected by flow cytometry revealed that PAK1 silencing attenuated cell cycle progression, inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses by modulating CREB expression and activation in xenograft models. Conclusion: These results suggest a novel mechanism whereby the PAK1–CREB axis drives carcinogenesis of squamous-cell carcinomas, and have important implications in the development of targeted therapeutics for squamous-cell lung cancer

Solvothermal Synthesis and Characterization of Chalcopyrite CuInSe2 Nanoparticles

The ternary I-III-VI2 semiconductor of CuInSe2 nanoparticles with controllable size was synthesized via a simple solvothermal method by the reaction of elemental selenium powder and CuCl as well as InCl3 directly in the presence of anhydrous ethylenediamine as solvent. X-ray diffraction patterns and scanning electron microscopy characterization confirmed that CuInSe2 nanoparticles with high purity were obtained at different temperatures by varying solvothermal time, and the optimal temperature for preparing CuInSe2 nanoparticles was found to be between 180 and 220 °C. Indium selenide was detected as the intermediate state at the initial stage during the formation of pure ternary compound, and the formation of copper-related binary phase was completely deterred in that the more stable complex [Cu(C2H8N2)2]+ was produced by the strong N-chelation of ethylenediamine with Cu+. These CuInSe2 nanoparticles possess a band gap of 1.05 eV calculated from UV–vis spectrum, and maybe can be applicable to the solar cell devices

Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression

The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ0) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ0 cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions