The Association of Elevated 2′,5′-Oligoadenylate-Dependent RNase L with Lung Cancer Correlated with Deficient Enzymatic Activity and Decreased Capacity of RNase L Dimerization

RNase L mediates critical cellular functions including antiviral, proapoptotic, antiproliferative and tumor suppressive activities. In this study, the expression and function of RNase L in lung cancer cells were examined. Interestingly we have found that the expression of RNase L in lung cancer cells was 3- and 9-fold higher in its mRNA and protein levels, but a significant decrease of its enzymatic activity when compared to that in corresponding normal lung cells. Further investigation revealed that 2-5A-induced dimerization of the RNase L protein, a necessary prerequisite for activation of RNase L, was inhibited, as a result of that RLI, a specific inhibitor of RNase L, was remarkably up-regulated in the cancer cells. Our findings provide new insight into how cancer cells escape normal growth-regulating mechanisms to form a tumor and the information may be useful for the design of novel strategies for treating lung cancer through regulating RNase L activity

Function modification of SR-PSOX by point mutations of basic amino acids

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis (AS) is a common cardiovascular disease. Transformation of macrophages to form foam cells by internalizing modified low density-lipoprotein (LDL) via scavenger receptor (SR) is a key pathogenic process in the onset of AS. It has been demonstrated that SR-PSOX functions as either a scavenger receptor for uptake of atherogenic lipoproteins and bacteria or a membrane-anchored chemokine for adhesion of macrophages and T-cells to the endothelium. Therefore, SR-PSOX plays an important role in the development of AS. In this study the key basic amino acids in the chemokine domain of SR-PSOX have been identified for its functions.</p> <p>Results</p> <p>A cell model to study the functions of SR-PSOX was successfully established. Based on the cell model, a series of mutants of human SR-PSOX were constructed by replacing the single basic amino acid residue in the non-conservative region of the chemokine domain (arginine 62, arginine 78, histidine 80, arginine 82, histidine 85, lysine 105, lysine 119, histidine 123) with alanine (designated as R62A, R78A, H80A, R82A, H85A, K105A, K119A and H123A, respectively). Functional studies showed that the mutants with H80A, H85A, and K105A significantly increased the activities of oxLDL uptake and bacterial phagocytosis compared with the wild-type SR-PSOX. In addition, we have also found that mutagenesis of either of those amino acids strongly reduced the adhesive activity of SR-PSOX by using a highly non-overlapping set of basic amino acid residues.</p> <p>Conclusion</p> <p>Our study demonstrates that basic amino acid residues in the non-conservative region of the chemokine domain of SR-PSOX are critical for its functions. Mutation of H80, H85, and K105 is responsible for increasing SR-PSOX binding with oxLDL and bacteria. All the basic amino acids in this region are important in the cells adhesion via SR-PSOX. These findings suggest that mutagenesis of the basic amino acids in the chemokine domain of SR-PSOX may contribute to atherogenesis.</p

The Application of Advanced Materials on the Water or Wastewater Treatment

Water scarcity is being recognized as a present and future threat to human activity, and, as a consequence, water purification technologies are gaining major worldwide attention. Advanced materials have many properties, such as strong adsorption, enhanced redox, and photocatalytic properties, providing unprecedented opportunities to treat surface water, groundwater, and industrial wastewater that are contaminated with toxic metals, organic and inorganic compounds, bacteria, and viruses. Currently, tremendous progress has been made in development of advanced materials for their environmental applications, and knowledge has been accumulated of the effects of these advanced materials on and their applications in the environment security, recycling, and reuse of raw materials and treatment agents, economic benefits, and potential problems to our society.This special issue aims to provide an up-to-date account of advancement in these areas as well as insights gained through field experience

Global intron retention mediated gene regulation during CD4+ T cell activation.

T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4(+) T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4(+) T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection

Differential Expressed Genes Identified Between African American and European American Keloid Fibroblasts

Keloids are benign fibroproliferative tumors due to dysregulation of collagen remodeling and abnormal wound healing. Although worldwide, there is a higher incidence of keloid disease (KD) in skin of color, little is known about this predisposition. In this study, we used one tissue micro array slide comprised of six AA and 6 EA punch biopsies of primary untreated keloid tissue from the head and neck area was created, following the NanoString® DSP Technology Access Program protocol. The GeoMx Human Whole Transcriptome Atlas Assay was performed, using morphology marker FAP. Polygonal region of interests selection strategy for Fibroblast Activation Protein (FAP) positive cells was conducted. Univariate analysis was performed, using linear regression models to identify differentially expressed genes (DEG) at a false discovery rate (FDR) of 0.05. Ingenuity pathway analysis (IPA) software was used to determine DEG pathway enrichment. 1,450 DEG were identified (p-va

Macrophage-Stimulated Cardiac Fibroblast Production of IL-6 Is Essential for TGF β/Smad Activation and Cardiac Fibrosis Induced by Angiotensin II

Interleukin-6 (IL-6) is an important cytokine participating in multiple biologic activities in immune regulation and inflammation. IL-6 has been associated with cardiovascular remodeling. However, the mechanism of IL-6 in hypertensive cardiac fibrosis is still unclear. Angiotensin II (Ang II) infusion in mice increased IL-6 expression in the heart. IL-6 knockout (IL-6-/-) reduced Ang II-induced cardiac fibrosis: 1) Masson trichrome staining showed that Ang II infusion significantly increased fibrotic areas of the wild-type mouse heart, which was greatly suppressed in IL-6-/- mice and 2) immunohistochemistry staining showed decreased expression of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and collagen I in IL-6-/- mouse heart. The baseline mRNA expression of IL-6 in cardiac fibroblasts was low and was absent in cardiomyocytes or macrophages; however, co-culture of cardiac fibroblasts with macrophages significantly increased IL-6 production and expression of α-SMA and collagen I in fibroblasts. Moreover, TGF-β1 expression and phosphorylation of TGF-β downstream signal Smad3 was stimulated by co-culture of macrophages with cardiac fibroblasts, while IL-6 neutralizing antibody decreased TGF-β1 expression and Smad3 phosphorylation in co-culture of macrophage and fibroblast. Taken together, our results indicate that macrophages stimulate cardiac fibroblasts to produce IL-6, which leads to TGF-β1 production and Smad3 phosphorylation in cardiac fibroblasts and thus stimulates cardiac fibrosis

Simultaneous removal of cadmium and nitrate in aqueous media by nanoscale zerovalent iron (nZVI) and Au doped nZVI particles

Nanoscale zerovalent iron (nZVI) has demonstrated high efficacy for treating nitrate or cadmium (Cd) contamination, but its efficiency for simultaneous removal of nitrate and Cd has not been investigated. This study evaluated the reactivity of nZVI to the co-contaminants and by-product formation, employed different catalysts to reduce nitrite yield from nitrate, and examined the transformation of nZVI after reaction. Nitrate reduction resulted in high solution pH, negatively charged surface of nZVI, formation of Fe3O4 (a stable transformation of nZVI), and no release of ionic iron. Increased pH and negative charge contributed to significant increase in Cd(II) removal capacity (from 40&nbsp;mg/g to 188&nbsp;mg/g) with nitrate present. In addition, nitrate reduction by nZVI could be catalyzed by Cd(II): while 30% of nitrate was reduced by nZVI within 2&nbsp;h in the absence of Cd(II), complete nitrate reduction was observed in the presence of 40&nbsp;mg-Cd/L due to the formation of Cd islands (Cd(0) and CdO) on the nZVI particles. While nitrate was reduced mostly to ammonium when Cd(II) was not present or at Cd(II) concentrations&nbsp;≥&nbsp;40&nbsp;mg/L, up to 20% of the initial nitrate was reduced to nitrite at Cd(II) concentrations&nbsp;&lt;&nbsp;40&nbsp;mg/L. Among nZVI particles doped with 1&nbsp;wt. % Cu, Ag, or Au, nZVI deposited with 1&nbsp;wt. % Au reduced nitrite yield to less than 3% of the initial nitrate, while maintaining a high Cd(II) removal capacity

Effects of nitrate on the treatment of lead contaminated groundwater by nanoscale zerovalent iron

Nanoscale zerovalent iron (nZVI) is efficient for removing Pb(2+) and nitrate from water. However, the influence of nitrate, a common groundwater anion, on Pb(2+) removal by nZVI is not well understood. In this study, we showed that under excess Fe(0) conditions (molar ratio of Fe(0)/nitrate&gt;4), Pb(2+) ions were immobilized more quickly (&lt;5 min) than in nitrate-free systems (∼ 15 min) due to increasing pH. With nitrate in excess (molar ratio of Fe(0)/nitrate&lt;4), nitrate stimulated the formation of crystal PbxFe3-xO4 (ferrite), which provided additional Pb(2+) removal. However, ∼ 7% of immobilized Pb(2+) ions were released into aqueous phase within 2h due to ferrite deformation. Oxidation-reduction potential (ORP) values below -600 mV correlated with excess Fe(0) conditions (complete Pb(2+) immobilization), while ORP values ≥-475 mV characterized excess nitrate conditions (ferrite process and Pb(2+) release occurrence). This study indicates that ORP monitoring is important for proper management of nZVI-based remediation in the subsurface to avoid lead remobilization in the presence of nitrate

The Application of Advanced Materials on the Water or Wastewater Treatment

Water scarcity is being recognized as a present and future threat to human activity, and, as a consequence, water purification technologies are gaining major worldwide attention. Advanced materials have many properties, such as strong adsorption, enhanced redox, and photocatalytic properties, providing unprecedented opportunities to treat surface water, groundwater, and industrial wastewater that are contaminated with toxic metals, organic and inorganic compounds, bacteria, and viruses. Currently, tremendous progress has been made in development of advanced materials for their environmental applications, and knowledge has been accumulated of the effects of these advanced materials on and their applications in the environment security, recycling, and reuse of raw materials and treatment agents, economic benefits, and potential problems to our society.This special issue aims to provide an up-to-date account of advancement in these areas as well as insights gained through field experience