Context: Sonchus oleraceus L. (Asteraceae) (SO) is a dietary and traditional medicinal plant in China. However, its underlying mechanism of action as an anti-inflammatory agent is not known. Objective: This study evaluates the anti-inflammatory activity of aqueous extract of SO. Materials and methods: The extract of SO was used to treat RAW 264.7 cells (in the working concentrations of 500, 250, 125, 62.5, 31.3 and 15.6 μg/mL) for 24 h. Pro-inflammatory cytokines and mediators produced in LPS-stimulated RAW 264.7 cells were assessed. Meanwhile, the expression level of TLR-4, COX-2, pSTATs and NF-κB was tested. Moreover, the anti-inflammatory activity of the extract in vivo was assessed using xylene-induced mouse ear oedema model and the anti-inflammatory compounds in the extracts were analyzed by HPLC-MS. Results: SO extract significantly inhibited the production of pro-inflammatory cytokines and mediators at gene and protein levels with the concentration of 31.3 μg/mL, and suppressed the expression of TLR-4, COX-2, NF-κB and pSTAT in RAW 264.7 cells. The anti-inflammatory activity of SO in vivo has significant anti-inflammatory effects with the concentration of 250 and 125 mg/kg, and less side effect on the weights of the mice at the concentration of 250 mg/kg. Moreover, HPLC-MS analysis revealed that the anti-inflammatory compounds in the extract were identified as villosol, ferulaic acid, β-sitosterol, ursolic acid and rutin. Discussion and conclusion: This study indicated that SO extract has anti-inflammatory effects in vitro and in vivo, which will be further developed as novel pharmacological strategies in order to defeat inflammatory diseases.

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Angiogenesis plays an important role in many pathological processes. Identification of novel anti-angiogenic agents will provide new insights into the mechanisms for angiogenesis as well as potential lead compounds for developing new drugs. In the present study, a series of resveratrol methylated derivatives have been synthesized and screened. We found trans-3,4-dimethoxystilbene (3,4-DMS) with the fullest potential to develop as an anti-angiogenic agent. In vitro and in vivo analyses suggested that 3,4-DMS could effectively inhibit endothelial cell proliferation, migration, tube formation, and endogenous neovascularization. Our results showed that 3,4-DMS exerted its anti-angiogenic effect likely through induction of endothelial cell apoptosis via a pathway involving p53, Bax, cytochrome c, and caspase proteases. Moreover, 3,4-DMS also induced macroautophagy in endothelial cells through activation of AMPK and the downstream inhibition of mTOR signaling pathway. Further studies indicated that intracellular calcium ([Ca(2+)](i)) might bridge the 3,4-DMS-induced apoptosis and macroautophagy through modulating reactive oxygen species (ROS) levels in endothelial cells. Combination of 3,4-DMS with inhibitor of autophagy, such as 3-methyladenine (3-MA) and autophagy-related gene (ATG) 5 small interfering RNA (siRNA), potentiated the pro-apoptotic and anti-angiogenic effects of 3,4-DMS. Our study provides a novel angiogenic inhibitor and a useful tool in exploring the molecular mechanisms for the crosstalk between apoptosis and macroautophagy in endothelial cells. 3,4-DMS could be served as a potential lead compound for developing a class of new drugs targeting angiogenesis-related diseases.

Abstract:Four underground resources have been seen as having a long-term potential to support sustainable urban development: underground space, groundwater, geomaterials and geothermal energy. Utilization of these resources proposes a new paradigm of economic development: underground urbanism. The new management approach named "Deep City Method" is put forward to aid decisionmakers to integrate global potential of the urban underground into city-scale strategic planning. The research output will be presented in form of two papers each with a different focus. Part 1 aims to introduce the concept, process and initial application in Switzerland; Part 2 is devoted to show methodological insight for a new zoning policy in China and investment scenarios for project cost viability. This Part 1 paper will begin by presenting the fundamental concept of the Deep City Method, followed by a proposition for a trans-institutional planning process. The application is firstly based on a rating system to identify cities having a potential for underground development. The city of Geneva is selected for conceptual application and strategic level study. Further operational steps are required in order to generalize the concept to other cities around the world.

Abstract:Four underground resources have been seen as having long-term potential to support sustainable urban development: underground space, groundwater, geomaterials and geothermal energy. Utilization of these resources proposes a new paradigm of economic development: underground urbanism. The new management approach named "Deep City Method" is put forward to aid decisionmakers to integrate global potential of the urban underground into city-scale strategic planning. The research output will be presented in form of two papers each with a different focus. Part 1 aims to introduce the concept, process and initial application in Switzerland; Part 2 is devoted to show methodological insight for a new zoning policy in China and investment scenarios for project cost viability.The Part 2 paper will demonstrate a comprehensive evaluation methodology for underground resources beneath the municipality of Suzhou in China, in order to formulate 3D land zoning. Strategic districts in Suzhou city of China are selected for feasibility outlook and policy instrument proposition. Finally, a new economic index "Underground cost efficiency premium" has been proposed to aid project developers to justify competitiveness of underground development.