This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted. The ratio of LC3-II/I and autophagic vacuoles were significantly increased at 24 h, but autophagy flux was blocked. The cleavage of caspase3 and PARP (poly ADP-ribose polymerase) were enhanced, while PC-12-sip53 cells exposed to 3-MA showed down-regulation of apoptosis. By contrast, the expression of autophagy-related genes and protein reduced in p53 overexpressing cells following a time dependent manner. Meanwhile, there was an increase in the expression of activated caspase3 and PARP, condensed and fragmented nuclei were evident. Conclusively, the data supported that silencing of p53 promotes impaired autophagy, which acts as a pro-apoptotic induction factor in PC-12 cells treated with colistin for 24 h, and overexpression of p53 inhibits autophagy and accelerates apoptosis. Hence, it has been suggested that p53 could not act as a neuro-protective target in colistin-induced neurotoxicity.

In the prevention and control of animal diseases, synbiotics combine the principles of probiotics and prebiotics, which play crucial roles in reducing intestinal disorders, such as diarrhea and indigestion, enhancing immune function, and decreasing the incidence of respiratory diseases in livestock and poultry. Following the confirmation of the prebiotic activity of lentinan, this study aimed to use microencapsulation technology to prepare synbiotics composed of Lactiplantibacillus plantarum (L. plantarum) and lentinan. The optimal preparation process for the synbiotic microcapsules was determined through single-factor, orthogonal, and response surface experiments. Subsequent experiments on storage stability, gastric acid tolerance, and intestinal release characteristics confirmed that the microencapsulated L. plantarum-lentinan synbiotic exhibited increased resistance to adverse environments. The microencapsulated synbiotic was ultimately incorporated into antibiotic-free feed at a dosage of 1 × 109 CFU/kg for broilers. The results indicated that this synbiotic could increase the average daily weight gain and feed conversion ratio of 28-day-old broiler chickens, increase the immune organ index, improve the morphology of the intestinal villi, and effectively increase the activity of digestive enzymes in the small intestine. Moreover, changes in the cecal microbial community composition of broilers were observed, with an increase in the number of Lactobacillus and a decrease in the number of Escherichia coli. In summary, this synbiotic can effectively enhance the growth performance of broilers, regulate the intestinal microbiota, improve immune function, and reduce the risk of intestinal and respiratory diseases in broilers.