Preparation of Colon-Targeted Acetylharpagide Tablets and its Release Properties in vivo and in vitro

Ethno Pharmacological Relevance: Acetylharpagide is a monomeric compound extracted from Ajuga decumbens, widely used for remedying infectious and inflammatory diseases in Southern China.Aim of the Study: The present study designed and investigated the formulation of colon-targeted acetylharpagide tablets according to the dual controlled release mechanisms of time-delay and pH-sensitivity.Materials and Methods: The core tablets of acetylharpagide were coated with the material used in time-delay systems such as ethyl cellulose and suitable channeling agent, followed by pH-dependent polymers, polyacrylic resin II and III in a combination of 1:4. Furthermore, the release and absorption performance of colon-targets tables were evaluated in vitro and in vivo. In the in vitro tests, the optimized formulation was not released in simulated gastric fluid in 2 h; the release was <5% at pH 6.8 simulated intestinal fluids for 4 h; the drug was completely released within 5 h at pH 7.6 simulated colon fluid. In the in vivo tests, pharmacokinetic characteristics of the colon-targeted tablets were investigated in dogs.Results: The results indicated that the acetylharpagide tablets with the technology of colon-targeting caused delayed Tmax, prolonged absorption time, lower Cmax, and AUCINF_obs. Meanwhile, the apparent volume of distribution (Vz_F_bs) of the colon-target tablets was higher than the reference.Conclusions: These results suggested that colon-targeted acetylharpagide tablets deliver the drug to the colon. The in vitro performance of colon-targeted acetylharpagide tablet was appropriately correlated with its performance in vivo

Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC. METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. CONCLUSION: This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation

N-Heterocyclic Carbene–Palladium Functionalized Coordination Polymer (Pd-NHC@Eu-BCI) as an Efficient Heterogeneous Catalyst in the Suzuki–Miyaura Coupling Reaction

In the present work, a new heterogeneous catalyst Pd-NHC@Eu-BCI was synthesized by introducing N-heterocyclic carbene–palladium active sites into a 2D coordination polymer [Eu(BCI)(NO3)2H2O]n (Eu-BCI) based on a 1,3-bis(carboxymethyl)imidazolium (HBCI) ligand. The catalyst was characterized by various analytical techniques such as X-ray photoelectron spectroscopy (XPS), inductively coupled plasma atomic emission spectroscopy (ICP-AES), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), infrared spectroscopy (IR) and thermogravimetric analysis (TGA). Catalytic activity of Pd-NHC@Eu-BCI was tested for the Suzuki–Miyaura cross-coupling reaction. The catalyst from the reaction mixture was easily recovered by filtration and still exhibited good catalytic activity and maintained its original structure after five cycles

The two-phase flow, transport mechanism and performance studies for PEM fuel cells

Both theoretical and experimental approaches have been used to study the inherent two-phase flow, transport mechanism and the performance for PEM fuel cells.A two-dimensional mathematical model with a complete set of governing equations for all the components of a PEM fuel cell is developed. The model couples the flow, species, potential and current density distributions in the cathode and anode fluid channels, gas diffusers, catalyst layers and membrane respectively. A two-phase flow model is used in the cathode, with a detailed pseudo-homogeneous model in the catalyst layer and coupled water fluxes among different components in the PEM fuel cell.The modeling results of typical hydrogen, oxygen, water concentration distribution in the anode, the cathode and the membrane are presented. The coupling of species concentration, current density, overpotential and potential is shown in the MEA direction, and the decrease of species concentration and local current density is shown in the flow direction. The two-phase flow characteristics in the cathode with varying operating conditions are studied.Both the experiment and the model are used to study two of the most critical PEM fuel cell operating issues, i.e., the water and heat management. The dependence of fuel and good agreements are reached.The study shows a coupled model is necessary to simulate the transport processes in the PEM fuel cell and a two-phase flow model is essential in the cathode side. The model provides a realistic transport simulation in the PEM fuel cell and may study the influences of many important geometric, physical and operation parameters; therefore, the model can be used to study the water and heat management scheme, as well as to improve the PEM fuel cell performance

Characteristics and applications of the cold heat exergy of liquefied natural gas

A mathematical model for predicting the low temperature exergy, pressure exergy and total cold heat exergy of Liquefied Natural Gas (LNG) is developed in this paper. In the model, the liquid mixture densities are calculated by a shape factor Corresponding State method, Vapor–Liquid-Equilibrium data of LNG are predicted by an improved method and the influences of real fluid effects are considered. The model is used to determine the various exergies, and the influences of ambient temperature, system pressure and mixture component concentrations on the cold heat exergies are analyzed. Different schemes for applying the low temperature exergy and pressure exergy are proposed. Based on the modeling results, it is proposed that the schemes for applying the cold heat exergies of LNG be determined by thermodynamic cycle optimization, while considering the magnitudes of low temperature exergy and pressure exergy, as well as the required gas supply pressures

A two-phase flow and transport model for PEM fuel cells

A two-phase flow and multi-component mathematical model with a complete set of governing equations valid in different components of a PEM fuel cell is developed. The model couples the flows, species, electrical potential, and current density distributions in the cathode and anode fluid channels, gas diffusers, catalyst layers and membrane, respectively. The modeling results of typical concentration distributions are presented. The coupling of oxygen concentration, current density, overpotential and potential are shown in the membrane electrode assembly (MEA). The model predicted fuel cell polarization curves for different cathode pressures compared well with our experimental data

A two-phase flow and transport model for the cathode of PEM fuel cells

A unified two-phase flow mixture model has been developed to describe the flow and transport in the cathode for PEM fuel cells. The boundary condition at the gas diffuser/catalyst layer interface couples the flow, transport, electrical potential and current density in the anode, cathode catalyst layer and membrane. Fuel cell performance predicted by this model is compared with experimental results and reasonable agreements are achieved. Typical two-phase flow distributions in the cathode gas diffuser and gas channel are presented. The main parameters influencing water transport across the membrane are also discussed. By studying the influences of water and thermal management on two-phase flow, it is found that two-phase flow characteristics in the cathode depend on the current density, operating temperature, and cathode and anode humidification temperatures

A parametric study of the cathode catalyst layer of PEM fuel cells using a pseudo-homogeneous model

A pseudo-homogeneous model for the cathode catalyst layer performance in PEM fuel cells is derived from a basic mass–current balance by the control volume approach. The model considers kinetics of oxygen reduction at the catalyst/electrolyte interface, proton transport through the polymer electrolyte and oxygen diffusion through porous media. The governing equations, a two-point boundary problem, are solved using a relaxation method. The numerical results compare well with our experimental data. Using the model, influences of various parameters such as overpotential, proton conductivity, catalyst layer porosity, and catalyst surface area on the performance of catalyst layer are quantitatively studied. Based on these results, cathode catalyst layer design parameters can be optimized for specified working conditions