Hierarchically Porous Gd3+-Doped CeO2 Nanostructures for the Remarkable Enhancement of Optical and Magnetic Properties

Rare earth ion-doped CeO2 has attracted more and more attention because of its special electrical, optical, magnetic, or catalytic properties. In this paper, a facile electrochemical deposition route was reported for the direct growth of the porous Gd-doped CeO2. The formation process of Gd-doped CeO2 composites was investigated. The obtained deposits were characterized by SEM, EDS, XRD, and XPS. The porous Gd3+- doped CeO2 (10 at% Gd) displays a typical type I adsorption isotherm and yields a large specific surface area of 135 m2/g. As Gd3+ ions were doped into CeO2 lattice, the absorption spectrum of Gd3+-doped CeO2 nanocrystals exhibited a red shift compared with porous CeO2 nanocrystals and bulk CeO2, and the luminescence of Gd3+-doped CeO2 deposits was remarkably enhanced due to the presence of more oxygen vacancies. In addition, the strong magnetic properties of Gd-doped CeO2 (10 at% Gd) were observed, which may be caused by Gd3+ ions or more oxygen defects in deposits. In addition, the catalytic activity of porous Gd-doped CeO2 toward CO oxidation was studied

In Vivo Imaging of Transiently Transgenized Mice with a Bovine Interleukin 8 (CXCL8) Promoter/Luciferase Reporter Construct

One of the most remarkable properties of interleukin 8 (CXCL8/IL-8), a chemokine with known additional functions also in angiogenesis and tissue remodeling, is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by several folds in response to proinflammatory cytokines, bacterial or viral products, and cellular stress. Although mouse cells do not bear a clear homologous IL-8 gene, the murine transcriptional apparatus may well be capable of activating or repressing a heterologous IL-8 gene promoter driving a reporter gene. In order to induce a transient transgenic expression, mice were systemically injected with a bovine IL-8 promoter–luciferase construct. Subsequently mice were monitored for luciferase expression in the lung by in vivo bioluminescent image analysis over an extended period of time (up to 60 days). We demonstrate that the bovine IL-8 promoter–luciferase construct is transiently and robustly activated 3–5 hours after LPS and TNF-α instillation into the lung, peaking at 35 days after construct delivery. Bovine IL-8 promoter–luciferase activation correlates with white blood cell and neutrophil infiltration into the lung. This study demonstrates that a small experimental rodent model can be utilized for non-invasively monitoring, through a reporter gene system, the activation of an IL-8 promoter region derived from a larger size animal (bovine). This proof of principle study has the potential to be utilized also for studying primate IL-8 promoter regions

Lycopene Inhibits NF-kB-Mediated IL-8 Expression and Changes Redox and PPARγ Signalling in Cigarette Smoke–Stimulated Macrophages

Increasing evidence suggests that lycopene, the major carotenoid present in tomato, may be preventive against smoke-induced cell damage. However, the mechanisms of such a prevention are still unclear. The aim of this study was to investigate the role of lycopene on the production of the pro-inflammatory cytokine IL-8 induced by cigarette smoke and the possible mechanisms implicated. Therefore, human THP-1 macrophages were exposed to cigarette smoke extract (CSE), alone and following a 6-h pre-treatment with lycopene (0.5–2 µM). CSE enhanced IL-8 production in a time- and a dose-dependent manner. Lycopene pre-treatment resulted in a significant inhibition of CSE-induced IL-8 expression at both mRNA and protein levels. NF-kB controlled the transcription of IL-8 induced by CSE, since PDTC prevented such a production. Lycopene suppressed CSE-induced NF-kB DNA binding, NF-kB/p65 nuclear translocation and phosphorylation of IKKα and IkBα. Such an inhibition was accompanied by a decrease in CSE-induced ROS production and NOX-4 expression. Lycopene further inhibited CSE-induced phosphorylation of the redox-sensitive ERK1/2, JNK and p38 MAPKs. Moreover, the carotenoid increased PPARγ levels which, in turn, enhanced PTEN expression and decreased pAKT levels in CSE-exposed cells. Such effects were abolished by the PPARγ inhibitor GW9662. Taken together, our data indicate that lycopene prevented CSE-induced IL-8 production through a mechanism involving an inactivation of NF-kB. NF-kB inactivation was accompanied by an inhibition of redox signalling and an activation of PPARγ signalling. The ability of lycopene in inhibiting IL-8 production, NF-kB/p65 nuclear translocation, and redox signalling and in increasing PPARγ expression was also found in isolated rat alveolar macrophages exposed to CSE. These findings provide novel data on new molecular mechanisms by which lycopene regulates cigarette smoke-driven inflammation in human macrophages

Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation

Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity

Social media as a platform for health-related public debates and discussions: the Polio vaccine on Facebook

BACKGROUND: Social media can act as an important platform for debating, discussing, and disseminating information about vaccines. Our objectives were to map and describe the roles played by web-based mainstream media and social media as platforms for vaccination-related public debates and discussions during the Polio crisis in Israel in 2013: where and how did the public debate and discuss the issue, and how can these debates and discussions be characterized? METHOD: Polio-related coverage was collected from May 28 to October 31, 2013, from seven online Hebrew media platforms and the Facebook groups discussing the Polio vaccination were mapped and described. In addition, 2,289 items from the Facebook group “Parents talk about Polio vaccination” were analyzed for socio-demographic and thematic characteristics. RESULTS: The traditional media mainly echoed formal voices from the Ministry of Health. The comments on the Facebook vaccination opposition groups could be divided into four groups: comments with individualistic perceptions, comments that expressed concerns about the safety of the OPV, comments that expressed distrust in the Ministry of Health, and comments denying Polio as a disease. In the Facebook group “Parents talk about the Polio vaccination”, an active group with various participants, 321 commentators submitted 2289 comments, with 64 % of the comments written by women. Most (92 %) people involved were parents. The comments were both personal (referring to specific situations) and general in nature (referring to symptoms or wide implications). A few (13 %) of the commentators were physicians (n = 44), who were responsible for 909 (40 %) of the items in the sample. Half the doctors and 6 % of the non-doctors wrote over 10 items each. This Facebook group formed a unique platform where unmediated debates and discussions between the public and medical experts took place. CONCLUSION: The comments on the social media, as well as the socio-demographic profiles of the commentators, suggest that social media is an active and versatile debate and discussion-facilitating platform in the context of vaccinations. This paper presents public voices, which should be seen as authentic (i.e. unmediated by the media or other political actors) and useful for policy making purposes. The policy implications include identifying social media as a main channel of communication during health crises, and acknowledging the voices heard on social media as authentic and useful for policy making. Human and financial resources need to be devolved specifically to social media. Health officials and experts need to be accessible on social media, and be equipped to readily provide the information, support and advice the public is looking for

The Influence of Substituents on the Tautomerism of Symmetrically Substituted 2,2'-Bis-benzimidazoles

The tautomerism of five symmetrically substituted 2,2'-bis-benzimidazoles [5(6),5'(6')-tetramethyl- (1); 5(6),5'(6')-dimethyl-(2); 5(6),5'(6')-dichloro- (3); 5(6),5'(6')-dimethoxy- (4) and 4(7),4'(7')-dimethyl-2,2'-bis-benzimidazole (5)], was studied by means of ¹H NMR spectroscopy at variable temperatures, and the influence of the substituents on the energy barriers for tautomeric interconversion was interpreted with the aid of theoretical calculations

Protein phosphatase 2Cδ/Wip1 regulates phospho-p90RSK2 activity in lesional psoriatic skin

Mads K Rasmussen, Jakob Nielsen, Rasmus B Kjellerup, Stine M Andersen, Anne H Rittig, Claus Johansen, Lars Iversen, Borbala Gesser Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Objectives: P90 ribosomal S6 kinase (RSK) 1 and 2 are serine/threonine protein kinases believed to mediate proliferation and apoptosis via the extracellular signal-regulated kinases (ERK1/2) signaling pathway. Macrophage migration inhibitory factor (MIF) and epidermal growth factor (EGF) are activators of this pathway and are elevated in the serum of patients with psoriasis compared with healthy controls. Studies on COS-7 cell cultures have shown that protein phosphatase 2Cδ (PP2Cδ) decreases the activity of RSK2 following EGF stimulation. We therefore hypothesize that PP2Cδ regulates RSK2 activity in psoriasis. Methods: In paired biopsies from nonlesional (NL) and lesional (L) skins, we analyzed the level of RSK1, 2 phosphorylation and the expression of PP2Cδ isoforms, integrin-linked kinase-associated serine/threonine phosphatase (ILKAP) and wild-type p53-induced phosphatase 1 (Wip1) by Western blotting, immunofluorescence and coimmunoprecipitation with monoclonal antibody for RSK2. The induction of Wip1 by MIF or EGF was studied in cultured normal human keratinocytes.Results: The protein level of RSK1, 2 phosphorylated at T573/T577 was significantly increased in L compared with NL psoriatic skin, while phosphorylation at S380/S386 was reduced in L compared with NL psoriatic skin when assayed by Western blotting and immunofluorescence microscopy. ILKAP expression was significantly higher in L than in NL skin, whereas Wip1 was expressed in similar amounts but showed increased coimmunoprecipitation with RSK2 in L compared with NL psoriatic skin. In cultured normal human keratinocytes stimulated with MIF, Wip1 phosphorylation and Wip1 expression were increased after 24 hours, but not when costimulated with dimethyl fumarate (DMF). The increased coimmunoprecipitation of Wip1 with RSK2 was significantly induced by EGF or MIF activation at 24 hours and could be significantly inhibited by DMF or the ERK1/2 inhibitor PD98059. Conclusion: The complex formation of Wip1 with RSK2 indicates a direct interaction reducing P-RSK2 (S386) activation in L skin and indicates that Wip1 has a role in the pathogenesis of psoriasis. Keywords: P90 RSK1, 2, EGF, MIF, PP2Cδ/ILKAP, PP2Cδ/Wip