[Soluble Uric Acid Activates NLRP3 Inflammasome in Myocardial Cells Through Down-regulating UCP2].

OBJECTIVE: To determine the H9C2 cell damage and NLRP3 inflammasome activation trigged by soluble uric acid (UA). METHODS: H9C2 cells were treated with UA. The cellular damage was examined after 12 h, 24 h and 48 h of treatment using MTS and lactic dehydrogenase (LDH). The apoptosis of H9C2 cells was analyzed by flow cytometry (FCM). NLRP3 inflammasome activation was reflected by the protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase-1 detected by Western blot. The mitochondria and cytoplasm were separated and the release of cytochrome C was detected by Western blot to analyze the damage of mitochondria. The impacts of NAC, a ROS inhibitor, on the cell viability and NLRP3 inflammasome activation were analyzed. The expression of UCP2 was detected by Western blot and immunofluorescence (IF). RESULTS: Dose response and time dependent effects of UA on cellular damage and cell apoptosis was observed. UA up-regulated the expression of NLRP3 inflammasome-related molecules. UA damaged the mitochondria. NAC improved the cell viability and inhibited NLRP3 inflammasome activation. UA down-regulated the expression of UCP2. CONCLUSION: Soluble UA can down-regulate the expression of UCP2, damage the mitochondria and activate NLRP3 inflammasome, resulting in cellular damage of H9C2 cells.

Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 inflammasome activation.

NLRP3 inflammasome activation plays an important role in diabetic cardiomyopathy (DCM), which may relate to excessive production of reactive oxygen species (ROS). Gypenosides (Gps), the major ingredients of Gynostemma pentaphylla (Thunb.) Makino, have exerted the properties of anti-hyperglycaemia and anti-inflammation, but whether Gps improve myocardial damage and the mechanism remains unclear. Here, we found that high glucose (HG) induced myocardial damage by activating the NLRP3 inflammasome and then promoting IL-1ß and IL-18 secretion in H9C2 cells and NRVMs. Meanwhile, HG elevated the production of ROS, which was vital to NLRP3 inflammasome activation. Moreover, the ROS activated the NLRP3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP3. Inhibition of ROS and cytochrome c dramatically down-regulated NLRP3 inflammasome activation and improved the cardiomyocyte damage induced by HG, which was also detected in cells treated by Gps. Furthermore, Gps also reduced the levels of the C-reactive proteins (CRPs), IL-1ß and IL-18, inhibited NLRP3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP3 inflammasome by cytochrome c binding to NLRP3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS-mediated NLRP3 inflammasome activation.

Odd-Even Effect in Synthesis of Mesoporous Silica Using Long-Chain Acyl-L-Alanine Sodium Salt Templating.

In this research, hexagonal and cubic mesoporous silica with ordered parallel pore channels was synthesized using odd chain-length N-undecanoyl-L-alanine sodium salt and even chain-length N-lauroyl-L-alanine sodium salt as template respectively. Aminopropylsiloxane was used as the co-structure-directing agents (CSDA). The ordered mesostructure was characterized by infrared spectroscopy, small X-ray diffraction patterns (XRD), scanning electron microscope (SEM), trasmission electron microscope (TEM), and nitrogen sorption analysis. The results indicated that mesoporous silica which was prepared by asymmetric odd chain-length surfactants presented a looser strucuture with large volume than mesoporous silica prepared by the even chain-length surfactant. It led to the transformation from 2D hexagonal (p6mm) phase to cubic (Ia¯3d) mesophase.

Preparation and In Vivo Biodistribution of Ultra-Small Superparamagnetic Iron Oxide Nanoparticles with High Magnetic Targeting Response.

The ultra-small superparamagnetic iron oxide (USPIO) particles with high saturation magnetization and good superparamagnetism were prepared by reverse micro-emulsions using novel C16E15 as surfactant, which can reduce magnetic dipole-dipole interaction, hence decreasing the critical blocking temperature (TB). Powder X-ray diffraction (XRD), Infrared spectrum (FT-IR), Transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and Vibrating sample magnetometer (VSM) were used to characterize the magnetic particles. The higher ratio of Fe2+/Fe3+ caused redundant FeO on the USPIO surface. An in vitro approach model for simulating target delivery of USPIO particles to sites of interest was developed to illustrate the relationship between magnetic fluid retention rate and pole distance. In Vivo targeted interception and magnetic targeting bio-distribution of superparamagnetic particles were also investigated simultaneously. The results indicated that the USPIO had high ability for magnetic focusing in mimetic surrounding tissue surrounding blood vessels under the action of pulsed magnetic field. The USPIO nanoparticles will be fundamental in biomedical applications.