GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Reactive oxygen species and nitric oxide scavenging nanoparticles alleviating rheumatoid arthritis through adjusting the seeds and growing soils

Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

Application research of hot-melt extrusion in preparation of solid dispersion / 药学学报

Hot-melt extrusion (HME) is mainly used to enhance the dissolution rate and bioavailability of poorly water soluble drugs. It has many advantages, such as simple process, continuous operation, high efficiency, on-line monitoring and so on. HME provides an innovative approach, which has been concerned by pharmaceutical workers, for preparation of solid dispersion abroad. This article reviews recent advances on preparation of solid dispersion by HME in preparation processing, carrier materials and quality evaluation in order to further promote and apply HME in preparation of solid dispersion.

Preparation, characterization and content determination of cubic phase gel containing capsaicin / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare the cubic phase gel containing capsaicin and characterize its properties.</p><p><b>METHOD</b>The cubic phases gel composed of glycerol monoolein, capsaicin and water was made by self-emulsion technology. The characterization of cubic phase gel was carried out by cross-polarizing light microscopy (CPLM) and Small Angle X-Ray Scattering (SAXS). The capsaicin content was determined by HPLC analysis.</p><p><b>RESULT</b>Under CPLM, cubic phase gel showed dark background. SAXS scattering spectra showed the scattering peaks at 0.1096, 0.1334, 0.1557, 0.1883 A(-1) which was compatible with q1:q2:q3:q4 = mean square root of 2: mean square root of 3: mean square root of 4: mean square root of 6. It was well known that the scattering vector ratio was the characteristic of cubic phase and the internal structure was confirmed to be Pn3m (Q224). The linear range for capsaicin determination was 3.25 x 10(-4) - 2.08 x 10(-2) g x L(-1) (R2 = 1). The average recovery was 97.53% with RSD of 2.9% (n=9).</p><p><b>CONCLUSION</b>CPLM and SAXS technology are suitable to characterize the cubic phase gel The determination of the capsaicin content by HPLC is simple and reproducible.</p>