Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice

ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis,Lactobacillus casei,Bifidobacterium bifidum,and Lactobacillus acidophilus.This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits,and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8(SAMP8)mice.ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks.We observed that ProBiotic-4 significantly improved the memory deficits,cerebral neuronal and synaptic injuries,glial activation,and microbiota composition in the feces and brains of aged SAMP8 mice.ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier,decreased interleukin-6 and tumor necrosis factor-αat both mRNA and protein levels,reduced plasma and cerebral lipopolysaccharide(LPS)concentration,toll-like receptor 4(TLR4)expression,and nuclear factor-κB(NF-κB)nuclear translocation in the brain.In addition,not only did ProBiotic-4 significantly decreased the levels ofγ-H2 AX,8-hydroxydesoxyguanosine,and retinoic-acid-inducible gene-I(RIG-I),it also abrogated RIG-I multimerization in the brain.These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging,and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-κB signaling pathway and inflammatory responses.

RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells

To increase the efficacy of currently used anti-cancer genotoxins,one of the current efforts is to find agents that can sensitize cancer cells to genotoxins so that the efficacious doses of genotoxins can be lowered to reduce deleterious side-effects.In this study,we reported that a synthetic RasGAP-derived peptide GAP159 could enhance the effect of chemotherapeutic agent cisplatin(CDDP)in human colon carcinoma HCT116 cells.Our results showed that GAP159 significantly increased the CDDP-induced cytotoxicity and apoptosis in HCT116 cells.This synergistic effect was associated with the inhibitions of phospho-AKT,phospho-ERK and NF-κB.In mouse colon tumor CT26 animal models,GAP159 combined with CDDP significantly suppressed CT26 tumor growth,and GAP159 alone showed slight inhibitory effect.Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers.