Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway / 神经科学通报·英文版

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.

Isolation and tumorigenicity of CD133 + subpopulation in human hepatocellular carcinoma / 中华肝胆外科杂志

Objective To separate the CD133 + subpopulation in human hepatocellular carcinoma (HCC) and investigate the tumorigenicity.Methods The human liver cancer tissues were subcutaneously transplanted into nude mice to generate xenograft tumors which were then isolated to prepare single cell suspension.The expression of CD133 + subpopulation was further detected using flow cytometry.The CD133 + subpopulations were separated and depurated with magnetic-activated cell sorting system.Immunofluorescence was performed to identify the histological phenotype of CD133 + subpopulation.The in vitro and in vivo clone formation assay and in vivo xenograft formation assay were performed, respectively.Results Flow cytometry analysis revealed that a percentage of (4.1 ± 0.6) ％ CD133 + cells were detected in xenografts.Immunofluorescence studies showed that (86.8 ± 7.5) ％ of the isolated cells were CD133 +.Compared with CD133-population, CD133 + cells showed a higher capability to generate clone sphere in vitro and a higher tumorigenicity in nude mice (P ＜ 0.05).Conclusion The CD133 + subpopulation in human hepatocellular carcinoma had a potent tumorigenicity and was enriched in cancer stem cells.