Past mastering of metal transformation enabled physicians to increase their therapeutic potential.

BACKGROUND: Metals are trace elements, vital in some instances or toxic in others. Due to this toxicity, they have been used since ancient time as antimicrobials, and prescribed when plant-only remedies were not efficient enough. These remedies could still contain secrets that may lead to the discovery of new therapeutically interesting combinations. The objective of this study was to give a proof of concept that such remedies combining metals and plants are worth studying again. METHODS: We exploited 4 medical formularies (aqrabadhin), from three Arab authors from the 9-12th century. We reproduced a remedy, and analyzed the role of each ingredient. We further looked for the minimum inhibitory concentration against three pathogenic bacteria, and we analyzed toxic and inflammatory effects of this remedy on macrophages. RESULTS: Even if plants were extensively used (almost 80 % of all ingredients), more than 36 different minerals have been found in these 4 aqrabadhin. When it came to remedies against infections that could be applied externally, the use of metals grew to 70 %. We focused on a remedy, containing mainly metals. We have been able to attribute a role for each ingredient, to show that this skin remedy helped to combat the infection and to resorb the wound, and to highlight the mastering of metal transformation by these physicians. CONCLUSIONS: With a very simple recipe, mainly composed of metals, these past physicians designed a complete and synergistic remedy to combat abscesses, while restricting the toxic effect of metals to the site of infection. It is a first example showing that different metal manufactures were evolved to improve their therapeutic potentials. The knowledge acquired by these physician should deserve more attention, and unexpected features, original organo-metallic compounds or therapeutic synergy could still be found from such research.

Bioimaging Nucleic-Acid Aptamers with Different Specificities in Human Glioblastoma Tissues Highlights Tumoral Heterogeneity.

Nucleic-acid aptamers are of strong interest for diagnosis and therapy. Compared with antibodies, they are smaller, stable upon variations in temperature, easy to modify, and have higher tissue-penetration abilities. However, they have been little described as detection probes in histology studies of human tissue sections. In this study, we performed fluorescence imaging with two aptamers targeting cell-surface receptors EGFR and integrin α5ß1, both involved in the aggressiveness of glioblastoma. The aptamers' cell-binding specificities were confirmed using confocal imaging. The affinities of aptamers for glioblastoma cells expressing these receptors were in the 100-300 nM range. The two aptamers were then used to detect EGFR and integrin α5ß1 in human glioblastoma tissues and compared with antibody labeling. Our aptafluorescence assays proved to be able to very easily reveal, in a one-step process, not only inter-tumoral glioblastoma heterogeneity (differences observed at the population level) but also intra-tumoral heterogeneity (differences among cells within individual tumors) when aptamers with different specificities were used simultaneously in multiplexing labeling experiments. The discussion also addresses the strengths and limitations of nucleic-acid aptamers for biomarker detection in histology.