Protective effect of quercetin against macrophage-mediated hepatocyte injury via anti-inflammation, anti-apoptosis and inhibition of ferroptosis.

Yinchenhao Decoction (YCHD) is a classic prescription in traditional Chinese medicine (TCM). It appears to play an important role in anti-inflammation and autoimmunity protection. As one of the key active ingredients in YCHD, quercetin is a novel anti-inflammatory metabolite that exerts protective effects in many autoimmune diseases. However, its role in autoimmune hepatitis (AIH)-related hepatic injury has not been studied. The aim of this study was to reveal the hepatocyte protective mechanism of quercetin. In this study, we used Concanavalin A (Con A) to establish an in vitro hepatocyte injury-associated AIH model. Brl3a hepatocyte injury was induced by the supernatant of J774A.1 cells treated with Con A. We found that quercetin mitigated Con A-induced via macrophage-mediated Brl3a hepatocyte injury. Quercetin administration reduced the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in the supernatant of Con A-treated Brl3a cells and attenuated the infiltration of J774A.1 macrophages induced by Con A. Moreover, quercetin effectively inhibited the expression of proinflammatory cytokines including interleukin-1ß (IL-1ß) by Con A. Furthermore, quercetin decreased hepatocyte apoptosis and ferroptosis levels in the macrophage-induced hepatocyte injury model. In conclusion, our study indicates that quercetin alleviates macrophage-induced hepatocyte damage by reducing the inflammatory response, apoptosis and ferroptosis. Our work suggests that quercetin might be a potential therapeutic strategy for AIH.

Distinct influence of inter- versus intra-trial feedback on the brain response to subsequent feedback: Evidence from event-related potentials.

Substantial evidence indicates that feedback processing not only varies with the valence of feedback, but is also highly dependent on contextual factors. Even so, the influence of prior outcome history on current outcome evaluation is far from clear. To investigate this issue, we conducted two event-related potential (ERP) experiments using a modified gambling task whereby each trial was associated with two consequences. In experiment 1, two instances of feedback indicated participant performance on two dimensions of a single decision, within a trial. In experiment 2, participants made two decisions in each trial, and then received two instances of feedback. We examined the feedback-related negativity (FRN) as an index of feedback processing. When both instances of feedback were relevant to the same trial (intra-trial), the FRN to the second was affected by the valence of the immediately previous feedback: The FRN was amplified to losses following wins. This was observed in both experiment 1 and experiment 2. When two instances of feedback were relevant to two different trials (inter-trial), the effect of immediately previous feedback on the FRN was inconsistent. In experiment 1 there was no effect of feedback from the previous trial on the FRN. However, in Experiment 2 there was an effect of inter-trial feedback on the FRN that was opposite to the effect of intra-trial feedback: The FRN was amplified when losses followed losses. Taken together, the findings suggest that the neural systems involved in reward processing dynamically and continuously integrate preceding feedback for the evaluation of present feedback.

Impact of Catalyst Deuteration on the Reactivity of Chiral Phase-Transfer Organocatalysts.

Site-specifically deuterated organocatalysts were prepared and found to show improved reactivity over the non-deuterated analogs. Two privileged C2 -symmetric chiral binaphthyl-modified tetraalkylammonium salts were selected for this study. The stability of these phase-transfer catalysts was generally improved by site-specific deuteration, though the degree of improvement was structure dependent. In particular, a large secondary kinetic isotope effect was observed for the tetradeuterated phase-transfer catalyst. The performance of these deuterated catalysts in the asymmetric catalytic alkylation of amino acid derivatives was better than that of non-deuterated analogs at low catalyst loadings. The results suggest that catalyst deuteration is a promising strategy for enhancing the stability and performance of organocatalysts.

Voluntary or reluctant? Social influence in charitable giving: an ERP study.

Social information has substantial influences on prosocial behavior. In this study, we performed an event-related potential (ERP) experiment to examine the effect of social influence on giving. The participants were allowed to form an initial decision on how much money to donate to a charity provided the program's average donation amount and to make a second donation decision. Social influence varied in different directions (upward, downward and equal) by altering the relative donation amount between the average donation amount and the participants' first donation amount. The behavioral results showed that participants increased their donation amount in the upward condition and decreased it in the downward condition. The ERP results revealed that upward social information evoked larger feedback-related negativity (FRN) amplitudes and smaller P3 amplitudes than in the downward and equal conditions. Furthermore, the pressure ratings, rather than the happiness ratings, were associated with the FRN patterns across the three conditions. We argue that people in social situations are more likely to increase their donations owing to pressure than voluntary altruism. Our study provides the first ERP evidence that different directions of social information evoke different neural responses in time course processing.

Construction and function analysis of the LncRNA-miRNA-mRNA competing endogenous RNA network in autoimmune hepatitis.

AIMS: To construct the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on our microarray chip data for providing new insights into the pathogenesis of autoimmune hepatitis. METHODS: The ceRNA pairs were obtained by calculating the co-expression relationships among the differentially expressed lncRNAs (DELs), differentially expressed microRNAs (DEMis), and differentially expressed mRNAs (DEMs) with Pearson correlation analysis and hypergeometric distribution. The data of the differentially expressed genes were obtained from our previous studies in the concanavalin A-induced AIH mouse model. The biological functions of the ceRNA network were revealed by carrying out the GO and KEGG enrichment analysis. The expression of some differentially expressed genes constructed in the ceRNA pair was validated, and the correlation to liver injury was analyzed. RESULTS: The mRNAs constructed in the ceRNA network were most significantly annotated in the GO terms of "inflammatory response" and enriched in "Cytokine-cytokine receptor interaction" and "MAPK signaling pathway". The differences in the expression of Gm38975, mmu-miR-125a-3p, and Map3k13 between the model group and control group were significant, and the expression of these genes at a transcriptional level was positively or negatively correlated to the activity of ALT and AST as well as the amount of MDA and NO. CONCLUSION: Our work is the first in its kind to predict and illustrate the comprehensive lncRNA-miRNA-mRNA ceRNA network associated with the etiopathogenesis of AIH. This study indicates to lay the foundation for revealing the potential roles of ceRNAs in the occurrence of AIH and provide novel treatment targets for this disease.

Evaluations from Superiors Matter More: Evidence from Behavior and Event-related Potentials.

As an essential feature of social groups, social hierarchies influence how people interact in daily life. However, it is unknown how external evaluations from peers at different levels in a social hierarchy influence feedback processing. In the current study, participants were instructed to establish a social hierarchy through a novel stick drawing task. With their status in the social hierarchy manipulated to be in the middle, participants received positive or negative evaluations from superiors and inferiors separately with ERPs signals recorded. Behaviorally, participants rated their happiness highest, and most quickly, after receiving positive evaluations from superiors. ERP results showed that P3 amplitude exhibited an interaction between social hierarchy and feedback valence, such that larger P3 amplitude was elicited by positive evaluations from superiors than any other condition, whereas the feedback-related negativity was only sensitive to the difference between high and low social statuses. Moreover, a generalized linear mixed model examining single-trial ERP data showed P3 amplitude correlated with happiness ratings as a function of feedback valence: a significant positive correlation in the positive feedback condition and a significant negative correlation in the negative feedback condition. P3 was also negatively correlated with RT across all conditions. These results demonstrate that brain activity associated with feedback processing predicted participants' emotion ratings and their decision time. Our study provides the first ERP evidence that positive feedback from superiors impacts neural activity related to reward processing differently than positive feedback from those of lower social standing.