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 cytotoxicity of PCN-224 were examined in both human hepatocytes L-02 cells and mouse macrophages RAW264.7. Furthermore, the effect of inflammation and autophagy were measured in L-02 cells. The results indicated that PCN-224 was engulfed in L-02 cells and subsequently resulted in morphological changes, cell membrane destruction, and oxidative stress in L-02 cells. PCN-224 might trigger inflammation by promoting the secretion of inflammatory factors such as Tumor necrosis factors (TNF-α) and Interleukin (IL-6). PCN-224 might induce autophagosome accumulation and subsequently autophagic dysfunction. Additionally, PCN-224 induced cytotoxicity in RAW264.7 cells and increased the protein levels of the inflammasome component NLR Family Pyrin Domain Containing 3 (NLRP3) molecular, which indicated its cellular effects in different cell types. All of these results will support the reasonable use of PCN-224.When developing new cosmetics, it is extremely important to consider the safety of consumers. Absence of potential irritancy is generally assessed using an OECD TG439 compliant Reconstructed Human Epidermis (RHE) systems and MTT assays, resulting in an irritant/not irritant classification. To gain insight into the irritancy of molecules/finished cosmetic products and to predict the outcome of irritation tests performed on subjects whatever their nature, we developed a test that uses skin explants and histological analysis. Results showed that this irritation test is sensitive enough to accurately and repeatably detect known irritants. If the diverse origin of the skin explants used led to variability in the histological alterations scored, the overall grading of irritancy is highly reproducible. Finally, when testing 120 non-alcoholic cosmetics of various galenic forms, comparison of data between the ex vivo irritation tests and of a 24-/48-h human patch test revealed a single false negative, very close to the limit, and a 10% false positive rate. It was not possible to calculate the sensitivity of the ex vivo irritation test; however, its specificity was 89.9% and its accuracy was 89.1%. Similar results, with a slightly higher false positive rate, were found when testing 49 alcoholic cosmetics. These values exceed the minimum requirements of OECD TG439.Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers.  https://www.selleckchem.com/products/su5402.html  We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment.The understanding of the impact of the non-canonical NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in several human diseases including autoimmune, inflammatory and cancers has been on the rise. This pathway induces the expression of several important genes involved in diverse biological processes. Though progress has been made in understanding the activation, regulation and biological functions of the non-canonical NF-κB signaling mechanism, no specific drug has been approved to target NF-κB inducing kinase (NIK), the key signaling molecule in this pathway. The inhibition of NIK can serve as a potential therapeutic strategy for various ailments, especially for the treatment of different types of human cancers. There are other targetable downstream molecules in this pathway as well. This review highlights the possible role of the non-canonical NF-κB pathway in normal physiology as well as in different cancers and discusses about various pharmacological strategies to modulate the activation of this pathway.