https://www.selleckchem.com/products/mk-28.html Some of the adverse side-effects such as leukocytosis, hyperinsulinemia, hypoglycemia and sensitization to histamine, caused by diphtheria, tetanus and whole cell pertussis (DTwP) vaccines are related to the presence of non-inactivated pertussis toxin (PTx) residues (NiPTxR). The CHO cell clustering assay is an in vitro assay to measure NiPTxR in DTwP vaccines based on the ability of active PTx to cause cellular clustering. To study the biochemical mechanism involved in the clustering effect in CHO cells induced by PTx and by two DTwP vaccines, the levels of total cyclic cAMP were measured and compared to those obtained after treatment with cholera toxin (CTx) able to induce CHO cells elongation instead of cell clustering. Our results showed an increment of cAMP levels by CTx and total cell elongation in CHO cells. However, changes in cAMP levels were not associated with the total clustering induced by PTx or by DTwP vaccines. The high correlation seen between the levels of NiPTxR in the DTwP vaccines determined by the in vivo lethal histamine sensitization (HIST) assay and the in vitro CHO cell clustering assay indicated that the latter could be a suitable alternative test to HIST assay for the toxicological approval and release of batches of DTwP vaccines in their final formulation for human use in accordance with the application of the 3R's principle.Metal-organic frameworks (MOFs) are innovative porous structures consisting of metal ions and organic ligands, which have been verified for extraordinary applications in nanomedicine and pharmaceuticals. PCN-224 is a type of Zr-based MOFs, which has recently emerged as one of the most attractive nanomaterials for various applications, such as drug delivery, bioimaging and cancer therapy due to its favorable and fascinating physical-chemical properties. However, the safety evaluation and the potential toxicological properties remain unclear. In this study, the general cy