The JNK Inhibitor XG-102 Protects against TNBS-Induced Colitis

The c-Jun N-terminal kinase (JNK)-inhibiting peptide D-JNKI-1, syn. XG-102 was tested for its therapeutic potential in acute inflammatory bowel disease (IBD) in mice. Rectal instillation of the chemical irritant trinitrobenzene sulfonic acid (TNBS) provoked a dramatic acute inflammation in the colon of 7–9 weeks old mice. Coincident subcutaneous application of 100 µg/kg XG-102 significantly reduced the loss of body weight, rectal bleeding and diarrhoea. After 72 h, the end of the study, the colon was removed and immuno-histochemically analysed. XG-102 significantly reduced (i) pathological changes such as ulceration or crypt deformation, (ii) immune cell pathology such as infiltration and presence of CD3- and CD68-positive cells, (iii) the production of tumor necrosis factor (TNF)-α in colon tissue cultures from TNBS-treated mice, (iv) expression of Bim, Bax, FasL, p53, and activation of caspase 3, (v) complexation of JNK2 and Bim, and (vi) expression and activation of the JNK substrate and transcription factor c-Jun. A single application of subcutaneous XG-102 was at least as effective or even better depending on the outcome parameter as the daily oral application of sulfasalazine used for treatment of IBD

Arachidonic acid metabolism in TNS-induced chronic and immunologic enteritis in rats, and the effect of 5-ASA

Inflammation of the rat distal intestine was induced by intradermal sensitization and subsequent multiple intrajejunal challenge with the hapten 2,4,6-trinitrobenzenesulphonic acid (TNBS) via an implanted catheter. The time course of the inflammatory reaction was followed by determination of the enteritis score and measurement of in vitro eicosanoid formation of homogenates of the gut after 0, 1, 2, 4, 7, 14 and 21 days of local daily challenge with 0.08% TNBS. There was a small initial increase of eicosanoid formation, reached at days 1 and 2, followed by a significant increase in metabolism of arachidonic acid on day 21. Although at day 1 a four-fold increase in inflammation score was reached, no further significant changes were observed during the following 3 weeks. The greatest increase in metabolite formation was observed in prostanoids TxB2, PGE2. and PGD2 and the 5-lipoxygenase product LTC4, whereas minor changes were found for LTB4 and other lipoxygenase products such as 12- and 15-HETE. The formation of these metabolites was already inhibited by low-dose 5-aminosalicylic acid (5-ASA), given orally twice daily during the 3 weeks challenge period, while the enteritis score was affected dosedependently

Concave curvature facets benefit oxygen electroreduction catalysis on octahedral shaped PtNi nanocatalysts

Studies that demonstrated enhanced electrocatalytic oxygen reduction activities of octahedral PtNi nanocatalysts have routinely motivated and explained their data by the structure-sensitivity of PtNi alloy surfaces in general, more specifically by the favourable performance of the annealed Pt3Ni(111) single crystal surface with a monoatomic Pt skin, in particular. In this contribution, we challenge this view and show that imperfect Ni-enriched {111} nanofacets with concave Pt curvature catalytically outperform flat, well-alloyed, locally ordered {111} and {100} nanofacets in cuboctahedral nanoparticles. To achieve this, we investigate the geometric, compositional, and morphological structure on the ensemble and on the individual particle level of PtNi alloy nano-octahedra. In particular, we track the correlations of these parameters after thermal annealing and link them to their catalytic activity. The level of local compositional and structural disorder appears to be a reliable descriptor and predictor for ORR activity – at least within a family of catalysts. After annealing up to 300 °C, concave Pt {111} facets, with partially flat Ni facets, remained most prevalent, resulting in nanoparticles with pronounced elemental anisotropy. At higher annealing temperature, concave Pt morphologies gave way to cuboctahedra with healed flat {111} and {100} alloy facets. The imperfect concave nano-octahedral catalysts with enhanced local disorder invariably outperformed more ordered particles, yet lagged behind in morphological stability. Faceted PtNi nano-cuboctahedra emerging at 400 °C ultimately offered the most reasonable balance between moderately high activity and good morphological stability. This is why we propose these cuboctahedral shaped Pt alloy nanoparticles as promising PEM cathode fuel cell catalyst of choice. While the present results do not invalidate the exceptional oxygen reduction activity of perfect Pt3Ni(111) “skin” single crystal surfaces, they shed new light on the decade old puzzle about structure–activity relationships of PtNi octahedral nanocrystals

Nanoparticle formation of deposited Ag n clusters on free standing graphene

Size-selected $Ag_{n}$-clusters on unsupported graphene of a commercial Quantifoil sample have been investigated by surface and element-specific techniques such as transmission electron microscopy (TEM), spatially-resolved inner-shell X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). An agglomeration of the highly mobile clusters into nm-sized Ag-nanodots of 2–3 nm is observed. Moreover, crystalline as well as non-periodic fivefold symmetric structures of the Ag-nanoparticles are evident by high-resolution TEM. Using a lognormal size-distribution as revealed by TEM, the measured positive binding energy shift of the air-exposed Ag-nanodots can be explained by the size-dependent dynamical liquid-drop model