Host–microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling

ABSTRACT

Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases.     

Investigations into the C‐deuteriation of aryl alkyl ketones using urea as a pro‐base in the presence of a deuterium donor

Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro‐base in the presence of a suitable deuterium donor. Copyright © 2006 John Wiley & Sons, Ltd.     

芳香烃受体与乳腺癌

芳香烃受体(AhR)是一种配体激活转录因子,可介导多环芳烃类化合物的毒性反应(包括致癌性),还参与一些重要的生物学过程,如信号转导、细胞分化、细胞凋亡等。近年来的研究发现,芳香烃受体在乳腺癌的发生发展中可能通过多种途径起促进作用,其中AhR与ER的抑制性交互应答可能解释为什么化学致癌物为主导致的乳腺癌仍为激素敏感性乳腺癌。以AhR为靶点治疗乳腺癌的实验研究为临床试用提供了依据。     

Duplication of distal 22q

We report on three patients with duplication of distal 22q. One patient is a de novo carrier of the translocation t(21;22) (p13;q11), the other two are offspring of a translocation carrier t(10;22) (q26;q12). The clinical manifestations of these patients demonstrate the variability of the dup(22q) syndrome.     

含双酚—A和杂环结构的聚芳醚酮的合成与表征

用苯酚、苯酐和水合肼合成了4-（4-羟苯基）-2,3-二氮杂萘酮-1,并与双酚-A和二苯甲酮聚合,得到含双酚-A和杂环结构的聚醚酮聚合物。用FT-IR、^13C-NMR、DSC、TGA和DMA等方法对聚合物进行了表征。结果表明,这种可溶性的非晶态聚合物有较高的Tg和很高的耐热温度,Tg随聚合物的组成不同而变化（158-224℃）,5%热失重温度为444-541℃。     

Correlation between gene expression of aryl hydrocarbon receptor (AhR), hydrocarbon receptor nuclear translocator (Arnt), cytochromes P4501A1 (CYP1A1) and 1B1 (CYP1B1), and inducibility of CYP1A1 and CYP1B1 in human lymphocytes.

The relationships between gene expression of aryl hydrocarbon receptor (AhR), aryl hydrocarbon receptor nuclear translocator (Arnt), cytochromes P4501A1 (CYP1A1), 1B1 (CYP1B1), CYP1A1, and the inducibility of CYP1A1 and CYP1B1 were determined in 32 cultivated human lymphocytes. Cytochrome P450 induction was performed by incubating lymphocytes with benzanthracene. The relative gene expression levels were determined by quantitative real-time RT-PCR assay. We found that gender is an important confounding factor for gene expression in cultivated lymphocytes. AhR, CYP1A1 and CYP1B1 levels in noninduced lymphocytes were significantly higher in female nonsmokers than in male nonsmokers (p < 0.05). Nevertheless, CYP1A1 and CYP1B1 inducibility was lower in female nonsmokers. CYP1A1 inducibility was higher in male smokers than in male nonsmokers (p < 0.05). After controlling for gender and cigarette smoking, AhR levels positively correlated with CYP1B1 levels and CYP1A1 inducibility (p < 0.01 and p = 0.03, respectively). Arnt levels also correlated with CYP1B1 levels in induced lymphocytes (p < 0.01). However, AhR levels were negatively correlated with CYP1B1 inducibility. These data indicate that AhR expression associates with individual variation of CYP1A1 inducibility and CYP1B1 expression in cultivated lymphocytes. Furthermore, gender and cigarette smoking are important confounding factors for gene expression levels in cultivated lymphocytes.     

上海郊区老年痴呆症病人α-雌激素受体及芳香烃受体基因多态性

目的：探索上海地区农民人群中α-雌激素受体基因(ER-α)及芳香烃受体基因(Ahr)不同基因形态和老年痴呆症高发风险的可能联系．方法：分别以PCR—RFLP和AS—PCR方法分析一组老年痴呆症患者(n=52)ER-α基因及Ahr基因的多态位点，同一地区的健康人群(n=125)为对照．结果：Alzheimer症病人ER-α基因两个位点突变形态频率显著高于对照人群(Pvu Ⅱ位点：P=0．023，OR=2．94，95％CI 1．13—7．71；Xba I位点：P=0．046，0R=2．28，95％ CI 1．003—5．17)．Ahr G1721A位点基因型频率在病人组和对照组间无显著差异．结论：ER-α基因多态性可能与Alzheimer症易感性个体差异有关，本工作不支持Ahr基因多态性与老年痴呆症高发风险间的可能关联．