Registries in immune thrombocytopenia (ITP) in Europe: the European Research Consortium on ITP (ERCI) network

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Accelerated Hydrolysis of Aspirin Using Alternating Magnetic Fields

The major problem of current drug-based therapy is selectivity. As in other areas of science, a combined approach might improve the situation decisively. The idea is to use the pro-drug principle together with an alternating magnetic field as physical stimulus, which can be applied in a spatially and temporarily controlled manner. As a proof of principle, the neutral hydrolysis of aspirin in physiological phosphate buffer of pH 7.5 at 40 °C was chosen. The sensor and actuator system is a commercially available gold nanoparticle (NP) suspension which is approved for animal usage, stable in high concentrations and reproducibly available. Applying the alternating magnetic field of a conventional NMR magnet system accelerated the hydrolysis of aspirin in solution

Cloaking nanoparticles with protein corona shield for targeted drug delivery

Targeted drug delivery using nanoparticles can minimize the side effects of conventional pharmaceutical agents and enhance their efficacy. However, translating nanoparticle-based agents into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems. Here, we present a targeting strategy for nanoparticles incorporated with a supramolecularly pre-coated recombinant fusion protein in which HER2-binding affibody combines with glutathione-S-transferase. Once thermodynamically stabilized in preferred orientations on the nanoparticles, the adsorbed fusion proteins as a corona minimize interactions with serum proteins to prevent the clearance of nanoparticles by macrophages, while ensuring systematic targeting functions in vitro and in vivo. This study provides insight into the use of the supramolecularly built protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems

Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors

Funder: AstraZenecaAbstract: BRAF and MEK1/2 inhibitors are effective in melanoma but resistance inevitably develops. Despite increasing the abundance of pro-apoptotic BIM and BMF, ERK1/2 pathway inhibition is predominantly cytostatic, reflecting residual pro-survival BCL2 family activity. Here, we show that uniquely low BCL-XL expression in melanoma biases the pro-survival pool towards MCL1. Consequently, BRAF or MEK1/2 inhibitors are synthetic lethal with the MCL1 inhibitor AZD5991, driving profound tumour cell death that requires BAK/BAX, BIM and BMF, and inhibiting tumour growth in vivo. Combination of ERK1/2 pathway inhibitors with BCL2/BCL-w/BCL-XL inhibitors is stronger in CRC, correlating with a low MCL1:BCL-XL ratio; indeed the MCL1:BCL-XL ratio is predictive of ERK1/2 pathway inhibitor synergy with MCL1 or BCL2/BCL-w/BCL-XL inhibitors. Finally, AZD5991 delays acquired BRAFi/MEKi resistance and enhances the efficacy of an ERK1/2 inhibitor in a model of acquired BRAFi + MEKi resistance. Thus combining ERK1/2 pathway inhibitors with MCL1 antagonists in melanoma could improve therapeutic index and patient outcomes

Stimuli Thresholds for Isomerization-Induced Molecular Motions in Azobenzene-Containing Materials.

We use large-scale molecular dynamics simulations of the isomerizations of azobenzene molecules diluted inside a simple molecular material to investigate the effect of a modification of the cis isomer shape on the induced diffusion mechanism. To this end we simulate incomplete isomerizations, modifying the amplitude of the trans-to-cis isomerization. We find thresholds in the evolution of the host molecules mobility with the isomerization amplitude, a result predicted by the cage-breaking mechanism hypothesis (Teboul, V.; Saiddine, M.; Nunzi, J. M.; Accary, J. B. J. Chem. Phys. 2011, 134, 114517) and by the gradient pressure mechanism theory (Barrett, C. J.; Rochon, P. L.; Natansohn, A. L. J. Chem. Phys. 1998, 109, 1505–1516.). Above the threshold the diffusion then increases linearly with the variation of the chromophore size induced by the isomerization

V\uf6gel in der Agrarlandschaft der Schweiz

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