Publications

Leukaemias, driven by mutations in haematopoietic stem cells (HSCs), rely on interactions with the bone marrow (BM) niche and other cell populations such as mesenchymal stromal cells (MSCs) for growth and survival. While chimeric antigen receptor (CAR) T-cell therapy shows promise for other haematological malignancies, its application to acute myeloid leukaemia (AML) is hindered by tumour heterogeneity and off-target toxicity. Combining CRISPR-Cas9 gene editing with CAR T-cell therapy has potential for selectively targeting AML cells while sparing healthy tissue. However, validating the efficacy of these treatments prior to clinical trial is hampered by the differences between humans and animal models typically used for pre-clinical testing. Furthermore, traditional in vitro models fail to replicate the complexity of the BM niche and often overestimate treatments' efficacy. Here, we present a bioengineered human-cell containing endosteal BM niche model combining a fibronectin-presenting polymeric surface and a synthetic peptide hydrogel (PeptiGel) that mimics native BM tissue's mechanical properties. This platform supports niche phenotypes in MSCs and HSCs and enables the evaluation of combined CRISPR-CAR T-cell therapy, demonstrating potential as a preclinical human model for testing novel therapies.

JTD Keywords: Cd33, Extracellular-matrix, Hematopoietic stem-cells, Immunotherapy, Insights, Maintenance, Vivo

The involvement of the oral microbiome (OM) in the pathophysiology of Alzheimer's disease and vascular dementia has been recognized epidemiologically, but the molecular mechanisms remain elusive. In this study, we uncovered the presence of OM-derived proteins (OMdPs) in brain extracellular vesicles (bEVs) from post-mortem Alzheimer's disease and vascular dementia subjects using unbiased metaproteomics. OMdP circulation in blood EVs was also confirmed in an independent cohort. Our findings also reveal that specific OMdPs are present in bEVs, with their levels varying with disease progression. Peptidome-wide correlation analyses further explored their exchange dynamics and composition within bEVs. In addition, we validated the ability of OM-derived EVs to cross the blood-brain barrier using a blood-brain barrier-on-a-chip model, confirming a potential route for bacterial-derived molecules to reach the central nervous system. Bioinformatics-driven interaction analyses indicated that OMdPs engage with key neuropathological proteins, including amyloid-beta and tau, suggesting a novel mechanism linking dysbiotic OM to dementia. These results provide new insights into the role of the OM in neurodegeneration and highlight OMdPs as potential biomarkers and therapeutic targets.

JTD Keywords: Alzheimers-disease, Communication, Expression, Gut microbiota, Health, Insights, Rna, Virulence factors

Nanoparticles represent a promising class of material for nanomedicine and molecular biosensing. The formation of a protein corona due to nonspecific particle-protein interactions is a determining factor for the biological fate of nanoparticles in vivo and strongly impacts the performance of nanoparticles when used as biosensors. Nonspecific interactions are usually highly heterogeneous, yet little is known about the heterogeneity of the protein corona that may lead to inter- and intraparticle differences in composition and protein distribution. Here, we present a super-resolution microscopic approach to study the protein corona on single silica nanoparticles and subsequent cellular interactions using multicolor stimulated emission depletion (STED) microscopy. We demonstrate that STED resolves structural features of protein corona on single particles including the distribution on the particle surface and the degree of protein internalization in porous particles. Using multicolor measurements of multiple labeled protein species, we determine the composition of the protein corona at the single-particle level. We quantify particle-to-particle differences in the composition and find that the composition is considerably influenced by the particle geometry. In a subsequent cellular uptake measurement, we demonstrate multicolor STED of protein corona on single particles internalized by cells. Our study shows that STED microscopy opens the window toward mechanistic understanding of protein coronas and aids in the rational design of nanoparticles as nanomedicines and biosensors.

JTD Keywords: insights, multicolor microscopy, nanoparticles, protein corona, quantification, size, sted microscopy, Fluorescence, Quantification, Sted microscopy

The design of catalysts with controlled selectivity at will, also known as catalytic plasticity, is a very attractive approach for the recycling of carbon dioxide (CO2). In this work, we study how catalytically active hydroxyapatite (HAp) and brushite (Bru) interact synergistically, allowing the production of formic acid or acetic acid depending on the HAp/Bru ratio in the catalyst. Raman, wide angle X-ray scattering, X-ray photoelectron spectroscopy, scanning electron microscopy and electrochemical impedance spectroscopy studies, combined with an exhaustive revision of the crystalline structure of the catalyst at the atomic level, allowed to discern how the Bru phase can be generated and stabilized at high temperatures. Results clearly indicate that the presence of OH– groups to maintain the crystalline structural integrity in conjunction with Ca2+ ions less bonded to the lattice fixate carbon into C1, C2 and C3 molecules from CO2 and allow the evolution from formic to acetic acid and acetone. In this way, the plasticity of the HAp-Bru system is demonstrated, representing a promising green alternative to the conventional metal-based electrocatalysts used for CO2 fixation. Thus, the fact that no electric voltage is necessary for the CO2 reduction has a very favorable impact in the final energetic net balance of the carbon fixation reaction. © 2021

JTD Keywords:

ethanol production & nbsp, brushite, co2 reduction, conversion, electrocatalytic reduction, electrode, formate, heterogeneous catalysis & nbsp, hydrogen evolution, insights, monetite, polarized hydroxyapatite,