Rabbit Anti-Human MLKL (a.a. 1-226) Polyclonal antibody

Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A. baumannii infection and established a central role for it in multiple cell death pathways. A. baumannii infection induced mixed cell death constituted of apoptosis, pyroptosis, and necroptosis. Mechanically, A. baumannii triggered TRIF-dependent type I IFN production, which in turn induced the expression of genes Zbp1, Mlkl, caspase-11, and Gsdmd via KAT2B-mediated and P300-mediated H3K27ac modification, leading to NLRP3 inflammasome activation, and potentially contributed to GSDMD-mediated pyroptosis and MLKL-dependent necroptosis. Our study offers novel insights into the mechanisms of type I IFN and provides potential therapeutic targets for infectious and inflammatory diseases.

Several studies have shown the toxic effect of zinc oxide nanoparticles (NZnO) on various cancer cells. This study aimed to assess the cellular death mechanism of the NZnO in MCF-7 human breast cancer cells. The cells were pretreated with zVAD (apoptosis inhibitor), 3-MA (an autophagy inhibitor), and Nec (a necroptosis inhibitor) for two hours, followed by their exposure to NZnO for 48 h. In the presence of Nec and 3-MA, NZnO significantly reduced proliferation and viability of MCF-7 cells while the apoptotic index and Bax/Bcl-2 ratio was significantly increased, compared to the only NZnO-treated cells. In the only NZnO-treated cells expression of Caspases-3 and Caspase-8 were up-regulated. NZnO with Nec and 3-MA could significantly increase expression of Caspase-3 and Caspase-9, but not Caspase-8 in the MCF-7 cells. NZnO in presence of zVAD and 3-MA significantly increased expression of RIPK1, RIPK3, and MLKL genes, compared to the only NZnO-treated cells. Furthermore, viability and proliferation of MCF-7 cells in NZnO with the apoptosis and autophagy inhbitors were lower than the other experimental groups. NZnO with apoptosis and necroptosis inhibitors could significantly increase cell viability, cell proliferation, and relative expression of autophagy-related genes such as LC3-II, Beclin-1, and ATG5, compared to the only NZnO-treated. According to the results of this study, the high toxicity of NZnO toward breast cancer cells mainly depends on activation of necroptosis and suppression of autophagy processes.