A clear relationship between the tau assemblies and toxicity has still to be established. To correlate the tau conformation with its proteotoxic effect in vivo we developed an innovative cell-worm-based approach. HEK293 cells expressing tau P301L under a tetracycline-inducible system (HEK T-Rex) were employed to produce different tau assemblies whose proteotoxic potential was evaluated using C. elegans. Lysates from cells induced for five days, significantly reduced the worm’s locomotor activity. This toxic effect was not related to the total amount of tau produced by cells or to its phosphorylation state but was related to the formation of multimeric tau assemblies, particularly tetrameric ones. We investigated the applicability of this approach for testing compounds acting against oligomeric tau toxicity, using doxycycline (Doxy) as prototype drug. Doxy affected the tau solubility and promoted the disassembly of already formed toxic aggregates in lysates of cells induced for five days. These effects translated into a dose-dependent protective action in C. elegans. These findings confirm the validity of the combined HEK T-Rex cells and C. elegans-based approach as a platform for pharmacological screening.

Tetracyclines are a group of antibiotics whose first representative was discovered over 70 years ago. Since then, they have been of great interest in dermatology. In addition to their antibacterial activity, they are able to inhibit metalloproteinases and exhibit anti-inflammatory, anti-apoptotic and antioxidant effects. The side effects have been thoroughly studied over the years. The most characteristic and important in daily dermatolgical practice are: phototoxicity, hyperpigmentation, onycholysis, photoonycholysis, induced lupus erythematosus, idiopathic intracranial hypertension. In this article, we summarize the use of tetracyclines in infectious diseases and inflammatory dermatoses, and further discuss indications where the efficacy and safety of tetracyclines have been highlighted over the past few years.

The present study employed a modifed QuEChERS method to systematically analyze the presence of fifteen Quinolones and seven Tetracyclines antibiotic residues in local animal food. Additionally, a multi-level-four-factor Box-Behnken design (BBD) within the framework of Response surface methodology (RSM) was utilized to evaluate the various factors affecting the detection efficiency of the sample pretreament procedure. The optimization was performed by Design Expert®, the factors including volume of the acetonitrle, the addition of formic acid, the duration of extract and the addition of EDTA were combined to experiment design until reach an optimal solution. Finally, the sample test was conducted by ultra-high performance liquid chromatography-quadrupole-linear ion trap mass spectrometry in both multiple reaction monitoring (MRM) and enhanced product ion (EPI) scan modes on a QTRAP® 5500 instrument. The overall average recoveries from actual samples fortified with 22 antibiotics at three levels ranged from 74.7 to 122.6% based on the use of matrix-fortified calibration with the variation ranging from 2.1 to 18.2% (n=6). The limits of detection and quantification were 0.3 μg kg-1 and 1.0 μg kg-1, respectively.