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Objective Re Du Ning Injection (RDN), a Chinese materia medica injection, is made from the extracts of Lonicerae Japonicae Flos, Gardeniae Fructus, and Artemisiae Annuae Herba. Since last decade, RDN has been widely used in China for the treatment of viral infection, fever, and inflammation. To assess the potential interacting of RDN with co-administered drugs, the inhibitory effects of RDN on the enzyme activities (CYP1A1, CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2) of rat liver microsomes were investigated by a cocktail method. Methods A sensitive and specific LC-MS method capable of simultaneous quantification of five metabolites in rat liver microsomes was developed and validated. Then RDN (0.625%–1.0%) was incubated with rat liver microsomes and specific substrates. The enzyme activities were expressed as the formation rate of the specific metabolites of the substrates (pmol · mg · protein −1 · min −1 ). Results RDN competitively inhibited the activities of CYP1A2 and CYP2C11, with inhibition constant ( K i ) values determined to be 0.18% and 0.63%, respectively. RDN exhibited the mixed inhibition on the activity of CYP2D1, with a K i value of 0.15%. The activities of CYP1A1 and CYP3A1/2 were not markedly inhibited even by 1.0% RDN. Conclusion RDN could inhibit the rat enzyme activities of CYP1A2, 2C11, and 2D1 in vitro with different inhibition modes, which is worthy of promoting safety and efficacy of RDN.

Comparative space-time thinking lies at the heart of spatiotemporally integrated social sciences. The multiple dimensions and scales of socioeconomic dynamics pose numerous challenges for the application and evaluation of public policies in the comparative context. At the same time, social scientists have been slow to adopt and implement new spatiotemporally explicit methods of data analysis due to the lack of extensible software packages, which becomes a major impediment to the promotion of spatiotemporal thinking. The proposed framework will address this need by developing a set of research questions based on space-time-distributional features of socioeconomic datasets. The authors aim to develop, evaluate, and implement this framework in an open source toolkit to comprehensively quantify the changes and level of hidden variation of space-time datasets across scales and dimensions. Free access to the source code allows a broader community to incorporate additional advances in perspectives and methods, thus facilitating interdisciplinary collaboration. Being written in Python, it is entirely cross-platform, lowering transmission costs in research and education.

To determine the fractalkine expression in the aorta of ApoE −/− mice and the effect of high-dose aspirin intervention on fractalkine expression and atherosclerotic lesion formation. Twenty-one male ApoE gene knockout mice were randomized into three groups to receive either placebo in addition to normal mice chow (n = 7), placebo in addition to a high-fat diet (n = 7), or aspirin (58 mg/kg/d) in addition to a high-fat diet (n = 7). After 12 weeks of study, the mice were euthanized and serum cholesterol, thromboxane B2, and $$ 6 - {\text{keto}} - {\text{PG}}{{\text{F}}_{1\alpha }} $$ were examined. Fractalkine and cyclooxygenase expression in aorta were measured and the atherosclerotic lesion analyzed. Pathology image analysis showed that the atherosclerotic plaque was the most extensive in the high-fat diet group while the addition of aspirin greatly reduced the severity of the plaque. Both RT-PCR analysis and immunohistochemical analysis showed that fractalkine expression was the strongest in the high-fat diet group and was significantly decreased by aspirin treatment. Serum thromboxane B2 was lowered by aspirin while $$ 6 - {\text{keto}} - {\text{PG}}{{\text{F}}_{1\alpha }} $$ and cholesterol remained unchanged. The results of our study indicate that high dose aspirin can improve the atherosclerotic lesion and suppress the fractalkine expression in murine aorta.

Fractalkine is an important chemokine mediating local monocyte accumulation and inflammatory reactions in the vascular wall. Aspirin inhibits inflammatory cytokine expression closely related to atherosclerosis through the way independent of platelet and cyclooxygenase (COX). There has been no report about the effect of aspirin on fractalkine expression. We aimed to determine the fractalkine expression in human umbilical vein endothelial cell (HUVEC) stimulated by tumor necrosis factor (TNF)-alpha and the effect of aspirin intervention.Six of 8 HUVEC groups received either different concentrations of aspirin (0.02, 0.2, 1.0, 5.0 mmol/L) or 40 micromol/L pyrrolidinecarbodithioc acid (PDTC) or 0.5 micromol/L NS-398. The other two groups were negative control and positive control (TNF-alpha-stimulated). After being incubated for 24 hours, cells of the 8 groups except the negative control one were stimulated with TNF-alpha (4 ng/ml) for another 24 hours. After that, the cells were collected for RNA isolation and protein extraction.Both mRNA and protein expressions of fractalkine in HUVEC were upregulated by 4 ng/ml TNF-alpha stimulation. Aspirin inhibited fractalkine expression in a dose-dependent manner at mRNA and protein levels. Nuclear factor-kappa B inhibitor, PDTC, effectively decreased the fractalkine expression. Fractalkine expression was not influenced by COX-2 selective inhibitor NS-398. COX-1 protein expression was not changed by either TNF-alpha stimulation or aspirin, PDTC, NS-398 intervention. Both mRNA and protein expression of COX-2 in HUVEC were upregulated by 4 ng/ml TNF-alpha stimulation. Aspirin decreased COX-2 expression in a dose-dependent manner at mRNA and protein levels.TNF-alpha-stimulated fractalkine expression is suppressed by aspirin in a dose-dependent manner through the nuclear factor-kappa B p65 pathway.