Anti-TF monoclonal antibody, clone QUG-03

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in photodynamic therapy (PDT) of cancer treatment as excellent regenerative photocatalysts. However, there are some challenges because of their poor dispersity. Transferrin (Tf) was tried to modify the surface of TiO2 NPs to reduce the aggregation, which further affected uptake and excretion on SMMC-7721 human liver cancer cells. Initially, TiO2 NPs modified with Tf (TiO2-Tf NPs) entered into the cells faster than the pure TiO2 NPs which remain attaching on the cell membrane after short-term co-incubation. Tf modification increased the rate and amount of cellular endocytosis. Both TiO2 NPs and TiO2 Tf NPs were observed in lysosomes after long-term co-incubation through clathrin-mediated endocytosis pathway. Expulsion of NPs was then observed and it was found that the exocytosis of TiO2-Tf NPs was fast in the first 24 h, and then slowed down gradually from 24 h to 144 h. Totally, existence of Tf decreased the exocytosis of TiO2 NPs. Furthermore, the differences of cytotoxicity and genotoxicity between TiO2 NPs and TiO2-Tf NPs show that surface-adsorbed Tf components provide some protection from the cytotoxic effect by reducing the production of intracellular ROS. TiO2-Tf NPs obviously affected cell cycle, indicating a significant G2/M phase cell cycle arrest. Our results offer a promising application of easily aggregated TiO2 NPs in the nanomedicine field.

Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in the developed world, yet no pharmacological therapy exists. Here, we hypothesize that the integration of multiple omic data represents an approach towards unveiling novel molecular networks in CAVD. Databases were searched for CAVD omic studies. Differentially expressed molecules from calcified and control samples were retrieved, identifying 32 micro RNAs (miRNA), 596 mRNAs and 80 proteins. Over-representation pathway analysis revealed platelet degranulation and complement/coagulation cascade as dysregulated pathways. Multi-omics integration of overlapping proteome/transcriptome molecules, with the miRNAs, identified a CAVD protein-protein interaction network containing seven seed genes (apolipoprotein A1 (APOA1), hemoglobin subunit beta (HBB), transferrin (TF), alpha-2-macroglobulin (A2M), transforming growth factor beta-induced protein (TGFBI), serpin family A member 1 (SERPINA1), lipopolysaccharide binding protein (LBP), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3) and immunoglobulin kappa constant (IGKC)), four input miRNAs (miR-335-5p, miR-3663-3p, miR-21-5p, miR-93-5p) and two connector genes (amyloid beta precursor protein (APP) and transthyretin (TTR)). In a metabolite-gene-disease network, Alzheimer's disease exhibited the highest degree of betweenness. To further strengthen the associations based on the multi-omics approach, we validated the presence of APP and TTR in calcified valves from CAVD patients by immunohistochemistry. Our study suggests a novel molecular CAVD network potentially linked to the formation of amyloid-like structures. Further investigations on the associated mechanisms and therapeutic potential of targeting amyloid-like deposits in CAVD may offer significant health benefits.