Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin‐bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells. 相似文献
Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H2O2. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability. 相似文献
Z‐ligustilide is a natural benzoquinone derivative found in many widely used Chinese herbal medicines such as Angelica sinensis (Oliv.) Diels as well as Ligusticum chuanxiong Hort and so on. It has been used as a part of traditional Chinese medicine and is also present in various Chinese medicine preparations. Pharmacokinetic studies have shown that Z‐ligustilide has poor oral bioavailability in rats due to severe first‐pass metabolic reactions. New evidence suggests that Z‐ligustilide has a wide range of pharmacological properties, including anticancer, antiinflammatory, anti‐oxidant as well as neuroprotective activities and so on. The literature discussed is derived from readily accessible papers spanning the early 1970s to the end of March 2019. Information were collected from journals, books, and online searches (Google Scholar, PubMed, Science Direct, Science Citation Index Finder, Springer link, and CNKI). This review intends to provide a comprehensive overview of the pharmacokinetics and pharmacology of Z‐ligustilide in recent years, with a focus on its biological properties and mechanisms, which is of great significance for Chinese medicine. 相似文献
1. Cytochrome P450 3A4 (CYP3A4) is an important member of the cytochrome P450 enzyme superfamily, with 33 allelic variants reported previously. Genetic polymorphisms of CYP3A4 can produce a significant effect on the efficacy and safety of some drugs, so the purpose of this study was to clarify the catalytic characteristics of 22 CYP3A4 allelic isoforms, including 6 novel variants in Han Chinese population, on the oxidative metabolism of amiodarone in vitro.
2. Wild-type CYP3A4*1 and other variants expressed by insect cells system were incubated respectively with 10–500?μM substrate for 40?min at 37?°C and terminated at ?80?°C immediately. Then these samples were treated as required and detected with ultra-performance liquid chromatography-tandem mass spectrometry used to analyze its major metabolite desethylamiodarone.
3. Among the 21 CYP3A4 variants, compared with the wild-type, the intrinsic clearance values (Vmax/Km) of two variants were apparently decreased (11.07 and 2.67% relative clearance) while twelve variants revealed markedly increased values (155.20~435.96%), and the remaining of seven variants exhibited no significant changes in enzyme activity.
4. This is the first time report describing all these infrequent alleles for amiodarone metabolism, which can provide fundamental data for further clinical studies on CYP3A4 alleles. 相似文献