Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells

RESUMEN: In recent years, the potential use of silica nanoparticles (SiNPs) among different biomedical fields has grown. A deep understanding of the physicochemical properties of nanoparticles (NPs) and their regulation of specific biological responses is crucial for the successful application of NPs. Exposure to NP physicochemical properties (size, shape, porosity, etc.) could result in deleterious effects on cellular functions, including a pro-inflammatory response mediated via activation of the NLRP3 inflammasome. The aim of this study was to evaluate the potential in vitro immunomodulatory effect of 12-nm and 200-nm SiNPs on the expression of pro-inflammatory cytokines and NLRP3 inflammasome components in human primary neutrophils and PBMCs. This study demonstrates that regardless of the size of the nanoparticles, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Induced IL-1β production after exposure to SiNPs suggests the involvement of NLRP3 inflammasome components participation in this process. In conclusion, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, our data suggest that the production and release of IL-1β possibly occurs through the formation of the NLRP3 inflammasome

Enhancement of Electrical Conduction and Phonon Scattering in Ga2O3(ZnO)9-In2O3(ZnO)9 Compounds by Modification of Interfaces at the Nanoscale

The Ga2O3(ZnO)9 and In2O3(ZnO)9 homologous phases have attracted attention as thermoelectric (TE) oxides due to their layered structures. Ga2O3(ZnO)9 exhibits low thermal conductivity, while In2O3(ZnO)9 possesses higher electrical conductivity. The TE properties of the solid solution of Ga2O3(ZnO)9-In2O3(ZnO)9 were explored and correlated with changes in the crystal structure. High-quality (1−x)Ga2O3(ZnO)9-(ZnO)9 (x = 0.0 to 1.0) ceramics were prepared by the solid-state route using B2O3 and Nd2O3 as additives. The crystal structures were analysed by x-ray diffraction, high-resolution transmission electron microscopy and atomic resolution scanning transmission electron microscopy–high-angle annular dark field imaging–energy dispersive x-ray spectroscopy (STEM–HAADF–EDS) techniques. A layered superstructure with compositional modulations was observed in all samples in the (1−x)Ga2O3(ZnO)9-xIn2O3(ZnO)9 system. All the ceramics exhibited nanoscale structural features identified as Ga- and In-rich inversion boundaries (IBs). Substitution of 20 mol.% In (x = 0.2) in the Ga2O3(ZnO)9 compounds generated basal and pyramidal indium IBs typically found in the In2O3(ZnO)m system. The (Ga0.8In0.2)2O3(ZnO)9 compound does not exhibit the structural features of the Cmcm Ga2O3(ZnO)9 compound, which is formed by a stacking of Ga-rich IBs along the pyramidal plane of the wurtzite ZnO, but features that resemble the crystal structure exhibited by the R3¯¯¯m In2O3(ZnO)m with basal and pyramidal indium IBs. The structural changes led to improved TE performance. For example, (Ga0.8In0.2)2O3(ZnO)9 showed a low thermal conductivity of 2 W/m K and a high power factor of 150 μW/m K2 giving a figure of merit (ZT) of 0.07 at 900 K. This is the highest ZT for Ga2O3(ZnO)9-based homologous compounds and is comparable with the highest ZT reported for In2O3(ZnO)9 homologous compounds

TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base

Proteomics as a quality control tool of pharmaceutical probiotic bacterial lysate products

Probiotic bacteria have a wide range of applications in veterinary and human therapeutics. Inactivated probiotics are complex samples and quality control (QC) should measure as many molecular features as possible. Capillary electrophoresis coupled to mass spectrometry (CE/MS) has been used as a multidimensional and high throughput method for the identification and validation of biomarkers of disease in complex biological samples such as biofluids. In this study we evaluate the suitability of CE/MS to measure the consistency of different lots of the probiotic formulation Pro-Symbioflor which is a bacterial lysate of heat-inactivated Escherichia coli and Enterococcus faecalis. Over 5000 peptides were detected by CE/MS in 5 different lots of the bacterial lysate and in a sample of culture medium. 71 to 75% of the total peptide content was identical in all lots. This percentage increased to 87–89% when allowing the absence of a peptide in one of the 5 samples. These results, based on over 2000 peptides, suggest high similarity of the 5 different lots. Sequence analysis identified peptides of both E. coli and E. faecalis and peptides originating from the culture medium, thus confirming the presence of the strains in the formulation. Ontology analysis suggested that the majority of the peptides identified for E. coli originated from the cell membrane or the fimbrium, while peptides identified for E. faecalis were enriched for peptides originating from the cytoplasm. The bacterial lysate peptides as a whole are recognised as highly conserved molecular patterns by the innate immune system as microbe associated molecular pattern (MAMP). Sequence analysis also identified the presence of soybean, yeast and casein protein fragments that are part of the formulation of the culture medium. In conclusion CE/MS seems an appropriate QC tool to analyze complex biological products such as inactivated probiotic formulations and allows determining the similarity between lots

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

Remote Manipulation of Droplets on a Flexible Magnetically Responsive Film

The manipulation of droplets is used in a wide range of applications, from lab-on-a-chip devices to bioinspired functional surfaces. Although a variety of droplet manipulation techniques have been proposed, active, fast and reversible manipulation of pure discrete droplets remains elusive due to the technical limitations of previous techniques. Here, we describe a novel technique that enables active, fast, precise and reversible control over the position and motion of a pure discrete droplet with only a permanent magnet by utilizing a magnetically responsive flexible film possessing actuating hierarchical pillars on the surface. This magnetically responsive surface shows reliable actuating capabilities with immediate field responses and maximum tilting angles of ???90??. Furthermore, the magnetic responsive film exhibits superhydrophobicity regardless of tilting angles of the actuating pillars. Using this magnetically responsive film, we demonstrate active and reversible manipulation of droplets with a remote magnetic force.open0

Holographic Correlation Functions for Open Strings and Branes

In this paper, we compute holographically the two-point and three-point functions of giant gravitons with open strings. We consider the maximal giant graviton in $S^5$ and the string configurations corresponding to the ground states of Z=0 and Y=0 open spin chain, and the spinning string in AdS$_5$ corresponding to the derivative type impurities in Y=0 or Z=0 open spin chain as well. We treat the D-brane and open string contribution separately and find the corresponding D3-brane and string configurations in bulk which connect the composite operators at the AdS$_5$ boundary. We apply a new prescription to treat the string state contribution and find agreements for the two-point functions. For the three-point functions of two giant gravitons with open strings and one certain half-BPS chiral primary operator, we find that the D-brane contributions to structure constant are always vanishing and the open string contribution for the Y=0 ground state is in perfect match with the prediction in the free field limit.Comment: 25 page

S-matrix for magnons in the D1-D5 system

We show that integrability and symmetries of the near horizon geometry of the D1-D5 system determine the S-matrix for the scattering of magnons with polarizations in AdS3 $\times$ S3 completely up to a phase. Using semi-classical methods we evaluate the phase to the leading and to the one-loop approximation in the strong coupling expansion. We then show that the phase obeys the unitarity constraint implied by the crossing relations to the one-loop order. We also verify that the dispersion relation obeyed by these magnons is one-loop exact at strong coupling which is consistent with their BPS nature.Comment: 40 pages, Latex, Role of Virasoro constraints clarified, version matches with published versio

Three-point correlators for giant magnons

Three-point correlation functions in the strong-coupling regime of the AdS/CFT correspondence can be analyzed within a semiclassical approximation when two of the vertex operators correspond to heavy string states having large quantum numbers while the third vertex corresponds to a light state with fixed charges. We consider the case where the heavy string states are chosen to be giant magnon solitons with either a single or two different angular momenta, for various different choices of light string states.Comment: 15 pages. Latex. v2: Misprints corrected. Published versio