[Prunetin inhibits TLR4/MyD88 pathway to attenuate intestinal epithelial inflammatory response and ameliorate mouse Crohn's disease-like colitis].

Objective To investigate the regulatory role of natural plant compound prunetin (PRU) on the intestinal epithelial inflammation and the barrier structure in Crohn's disease-like colitis. Methods A lipopolysaccharide (LPS)-induced inflammatory injury model of colonic organoids and a 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model were established to evaluate the effects of PRU on the intestinal epithelial inflammation and intestinal barrier. In addition, network pharmacological predictions, combined with in vitro and in vivo studies, were used to analyze the molecular mechanisms by which PRU modulates intestinal epithelial inflammation and intestinal barrier in CD-like colitis. Results PRU inhibited the release of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß in LPS-induced colonic organoids, and ameliorated the colitis symptoms in TNBS-induced mice, including body mass loss, elevated disease activity index and increased inflammation scores. Meanwhile, PRU promoted the expression of tight junction proteins (ZO-1 and claudin-1) and improved their translocation restoration in LPS-induced colonic organoids and TNBS-induced intestinal epithelial cells, while maintaining the intestinal barrier structure. Mechanistically, PRU targeted the Toll-like receptor 4 (TLR4) and inhibited the activation of the TLR4/myeloid differentiation primary response gene 88 (MyD88) signaling pathway. Conclusion PRU can antagonize TLR4/MyD88 signaling, thereby inhibiting intestinal epithelial inflammation and protecting against intestinal barrier damage, which helps ameliorate Crohn's disease-like colitis.

[Inhibition of CD96 enhances interferon-γ secretion by natural killer cells to alleviate lung injury in mice with pulmonary Chlamydia muridarum infection].

OBJECTIVE: To assess the effect of neutralizing CD96 on natural killer (NK) cell functions in mice with pulmonary Chlamydia muridarum infection and explore the possible mechanism. METHODS: Male BALB/c mice were randomly divided into infection group (Cm group), anti-CD96 treatment group (anti-CD96 group) and control group (n=5). In the former two groups, C. muridarum was inoculated via intranasal administration to establish mouse models of pulmonary C. muridarum infection, and the mice in the control group received intranasal administration of the inhalation buffer. In anti-CD96 group, the mice were injected with anti-CD96 antibody intraperitoneally at the dose of 250 µg every 3 days after the infection; the mice in Cm group received intraperitoneal injections of saline. The body weight of the mice was recorded daily. The mice were sacrificed 5 days after C. muridarum infection, and CD96 expression was detected by quantitative real-time PCR and Western blotting. HE staining and pathological scores were used to evaluate pneumonia of the mice. The inclusion body forming units (IFUs) were detected in the lung tissue homogenates to assess lung tissue chlamydia load. Flow cytometry and ELISA were used to assess the capacity of the lung NK cells to produce interferon-γ (IFN-γ) and regulate macrophages and Th1 cells. RESULTS: C. muridarum infection inhibited CD96 expression in NK cells of the mice. Compared with those in Cm group, the mice in antiCD96 mice showed significantly milder lung inflammation (P < 0.05) and reduced chlamydia load in the lung tissue (P < 0.05). Neutralizing CD96 with anti-CD96 significantly enhanced IFN-γ secretion by the NK cells (P < 0.05) and augmented the immunoregulatory effect of the NK cells shown by enhanced responses of the lung macrophages (P < 0.05) and Th1 cells (P < 0.05). CONCLUSIONS: Inhibition of CD96 alleviates pneumonia in C. muridarum-infected mice possibly by enhancing IFN-γ secretion by NK cells and augmenting the immunoregulatory effect of the NK cells on innate and adaptive immunity.

Modulation of income redistribution decisions by anodal tDCS over the medial prefrontal cortex.

One cause of the persistence of income inequality may be rooted in people's resistance to change the existing income distribution. Prior studies have shown that the medial prefrontal cortex (mPFC) may be associated with the decision making that influences income distribution. However, it is unclear whether the mPFC is involved in income redistribution tasks when third-party decision makers are unaffected by the outcome of the decision. In this study, we elucidate the neural mechanism underlying the tolerance of income inequality and the decision making that is related to income redistribution. By applying the transcranial direct current stimulation (tDCS) over the mPFC, we investigate whether the change in the activation of the mPFC can influence a subject's inclination to expropriate a rich person's endowment and transfer it to a poor person. The main finding is that the anodal stimulation significantly reduced the subject's inclination to redistribute wealth from the rich to the poor, and lowered the rate of accepting options for redistribution. However, the willingness of income redistribution did not change following the cathodal stimulation compared with the sham condition. The effect of the anodal stimulation was constant across three types of initial inequality. The stimulation effect is likely caused by the subject's enhanced loss aversion or desire to reinforce social hierarchies.

Anodal tDCS Over the Right Temporoparietal Junction Lowers Overbidding in Contests.

Overbidding, which means bidding over the Nash equilibrium, is commonly observed in competitive social interactions, such as a contest or auction. Recent neuroscience studies show that the right temporoparietal junction (rTPJ) is related to overbidding and associated with inferring the intentions of others during competitive interactions. The present study investigates the neural underpinnings of overbidding and how the rTPJ impacts bidding behavior by using tDCS to modulate the activation of the rTPJ. Participants completed a two-person proportional prize contest, in which overbidding was frequently observed and each participant's share of the prize was equal to the individual's expenditure divided by the aggregated expenditure. We observed a significant tDCS effect, i.e., participants' average expenditure and overbidding rate were significantly reduced in the anodal stimulation compared with the cathodal and sham stimulation. Possible explanations include that enhanced activity in the rTPJ via the anodal stimulation increased the accuracy of a participant's inference of the strategies of others, or a participant's concern for others, and thus helped the participant bid optimally. Our findings provide evidence supporting that the activation of the rTPJ in contests affects overbidding and bidding strategy, and further confirm that the rTPJ is involved in the inference of mental states in a competition context.