Background: Autophagy and apoptosis are two important physiological processes that determine cell survival or death in response to different stress signals. The regulatory mechanisms of these two processes share B-cell lymphoma-2 family proteins and AMBRA1, which are present in both the endoplasmic reticulum and mitochondria. B-cell lymphoma-2 family proteins sense different stresses and interact with AMBRA1 to regulate autophagy and apoptosis, which are respectively mediated by Beclin1 and Caspases. Therefore, we investigated how different levels of stress on B-cell lymphoma-2 family proteins that bind to AMBRA1 in the endoplasmic reticulum and mitochondria regulate the switch from autophagy to apoptosis. Methods: In this paper, we considered the responses of B-cell lymphoma-2 family proteins, which bind to AMBRA1 in both the endoplasmic reticulum and mitochondria, to two different levels of stress in a model originally proposed by Kapuy et al. We investigated how these two stress levels affect the transition from autophagy to apoptosis and their effects on apoptosis activation over time. Additionally, we analyzed how the feedback regulation in this model affects the bifurcation diagrams of two levels of stress and cell fate decisions between autophagy and apoptosis. Results: Autophagy is activated for minor stress in mitochondria regardless of endoplasmic reticulum stress, while apoptosis is activated for only significant stress in mitochondria. Apoptosis is only sensitive to mitochondria stress. The time duration before apoptosis activation is longer in the presence of high AMBRA1 levels with high endoplasmic reticulum and mitochondria stress. AMBRA1 can compete with B-cell lymphoma-2 family proteins to bind and activate Beclin1 and thus promote the autophagy process for a long time before apoptosis. Furthermore, apoptosis is prone to occur with increasing activation of Caspases, inactivation of Beclin1-A and the Michaelis constant of Caspases. Conclusion: A novel mathematical model has been developed to understand the complex regulatory mechanisms of autophagy and apoptosis. Our model may be applied to further autophagy-apoptosis dynamic modeling experiments and simulations.

Aim: Mifepristone, a synthetic steroid compound that induces abortion, was recently found to potentially pass into human milk. This study aimed to determine the effects of mifepristone administration to lactating mice on the development and reproduction of their progeny.Methods: Lactating mice were gavage fed with mifepristone (8 mg/kg) daily for 4 days either from days 1–4 or from days 7–10 of lactation; controls received only peanut oil. Growth, mortality rate, organ weight to bodyweight ratio, sex hormone at 20, 40 and 60 days, fertility of these F₁ progeny and litter size, sex ratio and mortality rate of the second generation were recorded.Results: No significant differences were observed in the average bodyweight, mortality rate of the female or male pups, and organ coefficient of uterus and ovaries of females in adulthood in comparison with the controls. However, the organ coefficient of testis at day 20 and 40 and testosterone concentration at day 60 were increased in male pups. Moreover, the reproductive capacity of the F₁ pups was unaffected by 4 days exposure to mifepristone via their mother's milk: time to birth of F₂ pups, litter size, sex ratio and mortality rate were similar to control F₁ pups.Conclusion: The study showed that treating lactating mice with 8 mg/kg mifepristone influenced only the organ coefficient of testis at day 40 and the testosterone concentration in male pups at day 60, however, it did not affect the development and fertility of female and male pups.