To enhance the accuracy of SEs in

To enhance the accuracy of SEs in eliminating cancer cells, the mAb recognized by specific KT 5720 on tumor cells were fused with SEs. Fab C215 or C242 fused with SEA promoted apoptosis in human colon carcinoma cells via Fas (Dohlsten et al., 1994, Litton et al., 1996). SEB-incorporated exosomes were purified from cancer cells, and the resulting product could likely induce apoptosis in breast cancer and ovary adenocarcinoma cell lines through the intrinsic pathway (Mahmoodzadeh-Hosseini et al., 2014, Mahmoodzadeh-Hosseini et al., 2015). To reduce the side effect and to improve the safety, site-directed substitutions of SEs were performed, and the SE mutants showed potential in killing human non-small-cell lung cancer cell line Calu-1 (Forsberg et al., 2001, Erlandsson et al., 2003). Although SE-containing fusion proteins are a novel cancer therapy, the issue of safety is still a concern because most experiments have been conducted in cell lines or animal models; human beings are more sensitive to SEs (Pinchuk et al., 2010).
Conclusion As a major human pathogen, S. aureus induces apoptosis in various cell types, which are also important in S. aureus infections (Xu and Mccormick, 2012, Aziz et al., 2014). Pharmacological intervention of apoptosis has been demonstrated to improve the outcome of several S. aureus infections, at least on the experimental level (Ulett and Adderson, 2006, Ayala et al., 2007). However, the mechanism by which S. aureus triggers apoptosis remains incomplete. Aside from the certain cell component of S. aureus (such as SPA) that potentially promotes apoptosis (Das et al., 2002), most cell apoptotic processes caused by S. aureus arise from the different kinds of secreted toxins. Among the known S. aureus toxins, α-toxin, PVL, SEs, and two secreted enzymes (SspB and coagulase) reportedly stimulate apoptosis despite the underlying mechanisms being extremely complicated. Fig. 1 summarizes the S. aureus toxins and their underlying mechanisms in promoting apoptosis, and Table 1 lists the cell types used and factors involved in the S. aureus toxin-induced apoptosis. A more thorough understanding of S. aureus-activated apoptosis is needed for both anti-infection and anti-cancer therapies. Future studies on both apoptotic prevention and reliable S. aureus toxin-based biological medicine will allow us to turn this old pathogen into a new treatment for human health.
Conflict of interests
Introduction Japanese encephalitis virus (JEV) causes severe viral encephalitis in humans and animals and the mortality of Japanese encephalitis (JE) caused by JEV infection is 25–30%, and up to 50% of surviving patients suffer neuropsychiatric sequelae (Ricklin et al., 2016; Ye et al., 2016; Impoinvil et al., 2013). JEV is primarily mosquitoe-borne with the exception of vector-free transmission between pigs (Ricklin et al., 2016). To date, the pathogenesis underlying JEV infection remains poorly understood. JEV genome encodes three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). JE caused by JEV infection is characterized by profound brain neuron death (Ashraf et al., 2016; Ghoshal et al., 2007). JEV invades the central nervous system (CNS) and triggers a robust inflammatory response, resulting in increased levels of cytokines such as tumor necrosis factor alpha (TNF-α) in the cerebrospinal fluid, which could play a defensive role by regulating host immune responses to eradicate virus or commence an irreversible inflammatory response, leading to neuron death (Chen et al., 2004). The in vitro JEV infection has been reported to induce the apoptosis of a number of cells such as human medulloblastoma cell TE671, human neuronal precursor cell NT-2, human promonocyte HL-CZ, mouse neuroblastoma cell N18, Baby Hamster Syrian Kidney cell BHK-21 (Huang et al., 2016). These findings together demonstrate that inflammatory response and apoptosis induced by JEV infection play crucial roles in Japanese encephalitis pathogenesis.