[Effects of paclitaxel loaded-drug micelles on cell proliferation and apoptosis of human lung cancer A549 cells].

This study was conducted to investigate the paclitaxel loaded by hydrazone bonds in poly(ethylene glycol)-poly(caprolactone) micelles (mPEG-PCL-PTX) on proliferation and apoptosis of human lung cancer A549 cells and its possible mechanisms of anti-tumor activity. The cell proliferation was measured with MTT assay. Flow cytometry were used to analyze the cell cycle. The cell apoptosis was analyzed using Hoechst/P staining. The expression levels of apoptotic genes expression in the mitochondrial apoptosis pathway were detected by RT-PCR and Western blotting, respectively. The mPEG-PCL-PTX could inhibit the proliferation of A549 cells and promote the apoptosis. The Bax, caspase-3 protein expression were increased while Bcl-2 protein expression was decreased in A549 cells. Results showed that the polymer containing hydrazone bond is non-toxic in vitro, the mPEG-PCL-PTX micelles can inhibit the proliferation and induce the apoptosis of A549 cells. Key words: paclitaxel; micelle; A549 cell; proliferation; cell cycle; apoptosis

[Use of open-path TDL technique and the backward Lagrangian stochastic model to monitor ammonia emission from summer maize field].

The backward Lagrangian stochastic dispersion model in conjunction with open-path tunable diode absorption spectroscopy was used to quantify ammonia emissions from farmland based on the high-temporal resolution data, aiming to provide innovative achievements to diagnose patterns of ammonia flux. The results indicate that the bLS dispersion technique using open-path lasers to measure atmospheric ammonia concentrations is suitable for determining ammonia emissions from farmland continuously, especially for characterizing diurnal characteristics of NH3 emissions. The ammonia emissions have a significant diurnal pattern with two emission peaks from urea applied to maize on a calcareous sandy loam fluvo-aquic soil in the North China Plain. We believe that the first peak starting at approximately 9:00 am is due to NH3 absorbed by the dew re-emission at night as the dew evaporates. The maximum of ammonia flux at 14:00 corresponds to the peak of soil temperature and solar radiation. The ammonia emission increased rapidly, but the duration of emission peaks lasted approximately 4 d. Cumulative NH3 emission was 25.3% of the applied N over the entire measurement period. The NH3 emissions measured with bLS dispersion technique and venting method had certain difference.

Using neural networks to determine the contribution of danshensu to its multiple cardiovascular activities in acute myocardial infarction rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshensu is an active water-soluble component from Salvia Miltiorrhiza, which has been demonstrated holding multiple mechanisms for the regulation of cardiovascular system. However, the relative contribution of danshensu to its multiple cardiovascular activities remains largely unknown. AIM OF THE STUDY: To develop an artificial neural network (NN) model simultaneously characterizing danshensu pharmacokinetics and multiple cardiovascular activities in acute myocardial infarction (AMI) rats. The relationship between danshensu pharmacokinetics (PK) and pharmacodynamics (PD) were evaluated using contribution values. MATERIALS AND METHODS: Danshensu was intraperitoneally injected at a single dose of 20mg/kg to AMI rats induced by coronary artery ligation. Plasma levels of danshensu, cardiac troponin T (cTnT), total homocysteine (Hcy) and reduced glutathione (GSH) were quantified. A back-propagation NN model was developed to characterize the PK and PD profiles of danshensu, in which the input variables contained time, area under plasma concentration-time curve (AUC) of danshensu and rat weights (covariate). Relative contribution of input variable to the output neurons was evaluated using neuron connection weights according to Garson's algorithm. The kinetics of contribution values was also compared and was validated using bootstrap resampling method. RESULTS: Danshensu exerted significant cTnT-lowering, Hcy- and GSH-elevating effect, and these marker profiles were well captured by the trained NN model. The calculation of relative contributions revealed that the effect of danshensu on the PD marker could be ranked as cTnT>GSH>Hcy, while the effect of AMI disease on the PD marker could be ranked in the following order: cTnT>Hcy>GSH. The activity of transsulfuration pathway was quite obvious under the AMI state. CONCLUSION: NN is a powerful tool linking PK and PD profiles of danshensu with multiple cardioprotective mechanisms, it provides a simple method for identifying and ranking relative contribution to the multiple therapeutic effects of the drug.

Pharmacokinetic interactions induced by content variation of major water-soluble components of Danshen preparation in rats.

AIM: To investigate the pharmacokinetic interactions induced by content variation of the main water-soluble components of Danshen injection in rats. METHODS: Intravenous Danshen injection (control) or Danshen injection with danshensu (DSS), protocatechuic aldehyde (PAL), salvianolic acid A (Sal A) or salvianolic acid B (Sal B) were administered to female Sprague Dawley rats. Plasma concentrations of DSS, Sal A, PAL and its oxidative metabolite protocatechuic acid (PA) were analyzed simultaneously with LC-MS/MS; concentrations of Sal B were determined by the LC-MS method. Non-compartmental pharmacokinetic parameters were calculated and compared for identifying the pharmacokinetic interactions among these components. RESULTS: Compared with the control group, the DSS, Sal A, and Sal B groups had significant increases in AUC(0-infinity) in response to elevated concentrations of PAL (by 78.1%, 51.0%, and 82.9%, respectively), while the clearances (CL) were markedly reduced (by 42.5%, 32.9%, and 46.8%, respectively). Similarly, Sal A increased the AUC(0-infinity) of DSS and Sal B (26.7% and 82.4%, respectively) and substantially decreased their clearances (21.4% and 45.6%, respectively). In addition, the pharmacokinetics of DSS and Sal B were significantly affected by the content variation of the other major components; the AUC(0-infinity) increased by 45.1% and 52.1%, respectively, the CL dropped by 29.6% and 27.1%, respectively, and the T(1/2) was decreased by 22.0% and 19.6%, respectively. CONCLUSION: Complex, extensive pharmacokinetic interactions were observed among the major water-soluble constituents in the Danshen injection. The content variation of PAL had the most significant effect on the pharmacokinetic behaviors of other major constituents. Furthermore, the pharmacokinetics of DSS and Sal B were the most susceptible to the content change of other components.

Spectroscopic characterization of intramolecular charge transfer of sodium 4-(N,N-dimethylamino)naphthalene-1-sulfonate.

In this paper, a new dual fluorescent N,N-dimethylaminonaphthalene derivative, sodium 4-(N,N-dimethylamino)naphthalene-1-sulfonate (SDMDNS), was reported. It was found that SDMDNS emits dual fluorescence only in highly polar solvent water but not in organic solvents such as methanol, dioxane and acetonitrile. Only a single broad band emission at ca. 420 nm was observed in the short wavelength region in organic solvents. The dual fluorescence of SDMDNS in water was found at 423 and 520 nm, respectively. Introduction of organic solvent as ethanol into aqueous solution of SDMDNS leads to blue shift of the long-wavelength emission, and this was evidently supported by introduction of cyclodextrin or surfactant in the aqueous solution. It indicates that a highly polar solvent was required to bring out dual fluorescence; furthermore, the short wavelength fluorescence is emitted from locally excited (LE) state and the long wavelength fluorescence is emitted from charge transfer (CT) state. The pH dependence of the dual fluorescence of SDMDNS demonstrates that the neutral form of the molecular has a higher ratio of CT band intensity to LE band. Temperature effect on the excited state of SDMDNS was also examined and gave stabilization enthalpy (-DeltaH ) of the CT reaction 8.7 kJ mol(-1).