OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

OBJECTIVE To develop and validate a physiologically based toxicokinetics and toxico?dynamics(PBTK/TD)model for chlorpyrifos(CPF)in rats following both oral and subcutaneous expo?sures to CPF. METHODS ①A PBTK/TD model was established with toxicokinetics and toxicodynam?ics data in literature,which was used for predicting contents of CPF and 3,5,6-trichloro-2-pyridinol (TCP)in blood and activities of acetylcholine esterase(AChE)in the plasma and brain of rats exposed to CPF.②Rats were given 50 mg · kg-1 CPF oral and 50 mg · kg-1 CPF sc simultaneously. Blood and brain samples were collected at 0,1,2,4,6,8,12,24 and 48 h,respectively,after CPF administration (n=5). CPF And TCP contents in plasma,activities of AChE in the plasma and brain were deter?mined,and compared with the simulation values by PBTK/TD model in order to validate the accuracy of the model. RESULTS It was predicted by the PBTK/TD model that after the administration (oral+sc) of CPF 20+20,10+30 and (30+10)mg · kg-1,the concentrations of CPF and TCP in plasma increased and then decreased with time in each group. The inhibitory level of AChE activity in the plasma was orally dose-dependent,while AChE activity of the brain was more sensitive to CPF subcutaneous exposure. The simulation values obtained by the PBTK/TD model were not significantly different from the experimental values obtained by co-administered CPF at(50+50)mg · kg-1. CONCLUSION This CPF PBTK/TD model can quantitatively estimate target tissue dosimetry and AChE inhibition.

OBJECTIVE Calculate the dietary exposure and exposure risk of Chinese consumers to acephate,using the margin of exposure method.METHODS Determine the bench mark dose of acephate by 21 -day gavage experiment of rats.According to the data from the 2002 National Diet and Nutrition Survey,the 2000 -2006 national food conta mination monitoring program,the 2005 -2006 export monitoring data of customs,calculate the dietary exposure of Chinese consumers to acephate by probabilistic assessment.Estimate the exposure risk by co mparing the margin of exposure with 100. RESULTS The bench mark dose of acephate was 0.75 mg·kg -1 ,the BMDL was 0.51 mg·kg -1 .The exposure of children was higher than that of adults.The proportion at risk of group 1 -6 y,7 -17 y and 18 y or higher was 5%,1 % and 0.1 %,respectively.CONCLUSION So me consumers was of dietary exposure risk to acephate.The high exposure of children should be of great concern.