Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

This study was aimed to investigate the effect of traditional Chinese medicine (TCM) compound "Ji-Sui-Kang (JSK)" on the differentiation of neural stem cells (NSCs).Drug serum of JSK was prepared.The primary NSCs were isolated and cultured.NSCs were identified.Fetal bovine serum (FBS) was used to induce differentiation of NSCs.Different doses of drug serum of JSK was added to intervene the differentiation.There were the high-,medium-,and low-dose group.The blank control group was also set.The β Ⅲ-tubulin and GFAP were used to detect the differentiation of NSCs.And then,it was compared with the control group without drug serum.Positive cells ofβ m-tubulin and GFAP in different visual fields were counted.And the percentage of positive cells in the total number of cells was calculated.Fluorescence microscope was used to conduct quantitative fluorescence experiments.The results showed that the cultured neurospheres were expressed of Nestin protein.The percentage ofβⅢ-tubulin positive cells in the high-,medium-and low-dose group of drug serum of JSK was significantly higher than that in the control group (P＜0.05).The percentage of GFAP positive cells in the high-,medium-and low-dose groups of drug serum of JSK was significantly lower than that in the control group (P＜0.05).And the high-dose group of drug serum of JSK was statistically significant compared with the middle-and low-dose group of drug serum of JSK (P＜0.01).It was concluded that TCM compound JSK promoted thedifferentiation of NSCs intoβⅢ-tubulin positive cells.It provided a basis for treatment of SCI with TCM.

Objective To clarify the effects of Jisuikang on expression levels of BDNF and NGF protein in serum of rats with spinal cord injury;To explore its probable mechanism to improve the axon regeneration microenvironment and resistance spinal cord injury.Methods Ninety SD rats were chosen to establish acute spinal cord injury model through modified Allen's method. 15 rats were chosen randomly as sham-operation group, and the other 75 rats were randomly divided into model group, prednisone group and high-, medium-, and low-doseJisuikang groups. All administration groups were given relevant medicine for gavage, while rats in sham-operation group and model group were given normal saline with the same volume for gavage. The activity and death condition of rats were recorded. Rats were put to death on the 3rd, 7th and 14th d of intervention for carotid artery blood collection. The expressions of BDNF and NGF in serum were detected by ELISA.Results After modeling, the rats in model group showed a typical paraplegia syndrome. 3 day after operation, BDNF showed no statistical significance between model group and prednisone group, while each treatment group showed significant difference when compared with prednisone group (P<0.05,P<0.01). 7 d and 14 d after operation, compared with the model group, BDNF of prednisone group and medium-dose Jisuikang group showed statistical significance, and there was no significant difference between prednisone group and medium-dose Jisuikang group (P<0.05,P<0.01). The expression of NGF in each treatment group at each time point with the prednisone group showed statistical significance. 3 d and 7 d after operation, among prednisone group, high- and medium-doseJisuikang groups, the expression of NGF was significantly higher than model group. 14 d after operation, compared with the model group, the expression of NGF in medium- and low-dose Jisuikang groups and prednisone group still maintained at a relatively high level, with statistical significance (P<0.05,P<0.01).Conclusion Jisuikang can effectively promote the expressions of BDNF and NGF in serum after spinal cord injury and maintained at a relatively high level, so as to improve the microenvironment of axonal regeneration and promote nerve regeneration.