Immunological relationship between Helicobacter pylori and anti-tumor necrosis factor α agents in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of diseases characterized by refractory and chronic inflammation of the bowel, which can be treated with biologics in clinical practice. Anti-tumor necrosis factor α (TNF-α) agents, which are among the most widely used biologics, alleviate the inflammatory activity in a variety of ways. Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa, which could cause chronic inflammation and even induce gastric cancer. However, it has been suggested that H. pylori has a potential protective role in IBD patients. Yet there has been limited research on the mechanisms of the effect of H. pylori infection in IBD patients, and whether there is an interaction between H. pylori and anti-TNF-α agents. This review aims to summarize the possible mechanisms of H. pylori and anti-TNF-α agents in the development and treatment of IBD, and to explore the possible interaction between H. pylori infection and anti-TNF-α agents.

[GLP-1 receptor activation effects the p38MAPK signal pathway in hepatic stellate cells].

OBJECTIVE: To investigate the effects of activation of the GLP-1 receptor on the p38MAPK signaling pathway in hepatic stellate cells (HSCs). METHODS: HSCs were isolated and identified according to morphological features; the levels of GLP-1R protein were determined by western blotting.The HSCs were randomly divided into a control grouP (normal saline treatment) and experimental grouP(liraglutide treatment); after 120 hours, the expression of p38MAPK mRNA was examined by RT-PCR and of phosphorylated (p)-p38MAPK protein was detected by western blotting. RESULTS: GLP-1R proteins were detected in the HSCs. Compared with the control group, the experimental group showed significantly decreased p38MAPK mRNA and p-p38MAPK protein (both P < 0.01). CONCLUSION: The p38MAPK signaling pathway could be down-regulated when GLP-1R is activated in HSCs.

Design, synthesis, and biological evaluation of diphenyl ether substituted quinazolin-4-amine derivatives as potent EGFRL858R/T790M/C797S inhibitors.

Epidermal growth factor receptor (EGFR) is a validated target for non-small-cell lung cancer (NSCLC). However, the treatment for EGFR-C797S mutation induced by third-generation EGFR inhibitors remains a concern. Therefore, the development of the fourth-generation EGFR inhibitors to overcome the EGFR-C797S mutation has great potential for clinical treatment. In this article, we designed and synthesized a series of diphenyl ether substituted quinazolin-4-amine derivatives that simultaneously occupy the ATP binding pocket and the allosteric site of EGFR. Among the newly synthesized compounds, 9d displayed excellent kinase activity against EGFRL858R/T790M/C797S with an IC50 value of 0.005 µM, and exhibited anti-proliferation activity in BaF3-EGFRL858R/T790M/C797S cells with the IC50 value of 0.865 µM. Furthermore, 9d could suppress phosphorylation of EGFR and induce cell apoptosis and cycle arrest at G2 phase in a dose-dependent manner in BaF3-EGFRL858R/T790M/C797S cells. More importantly, 9d displayed significant antitumor effects in BaF3-EGFRL858R/T790M/C797S xenograft mouse model (30 mg/kg, TGI = 71.14 %). All the results indicated compound 9d might be a novel fourth-generation EGFR inhibitor for further development in overcoming the EGFR-C797S resistance mutation.

Surface wettability of various phases of titania thin films: Atomic-scale simulation studies.

In the paper, the wettability of different phases of TiO2 thin films (anatase, brookite, and rutile) have been studied using molecular-dynamics simulation. The principle of micro-wetting is discussed. The simulation results show that the contact angle decreases upon increasing the interaction energy between the water and the titanium dioxide interface during the wetting process. The values of contact angles from large to small are: rutile, brookite and anatase. The calculated equilibrium contact angles are 73.9°, 59.2°, and 43.7°, respectively. The reason is that the structural connection and the arrangement of the surface microtopography directly affect the movement of water droplets on the surface of the material, thus affecting the wettability. In addition, the amount of the interaction energy and the radial distribution function between these three interfaces and the droplets are calculated, and the density change of the droplet is analyzed further which indicate the difference in wetting between the three crystal structures. At the same time, by simulating and comparing the wettability of the trench surface and the original surface of anatase, it is inferred that the rough interface increases the contact angle with the droplet and reduces the wettability.