ABSTRACT
<p><b>Objective</b>The objective of the study was to summarize the role of DNA methylation in the development and metastasis of uveal melanoma (UM).</p><p><b>Data Sources</b>The relevant studies in MEDLINE were searched.</p><p><b>Study Selection</b>In this review, we performed a comprehensive literature search in MEDLINE using "uveal melanoma" AND ("DNA methylation" OR "epigenetics") for original research/review articles published before February 2018 on the relationship between DNA methylation and UM. References of the retrieved studies were also examined to search for potentially relevant papers.</p><p><b>Results</b>Previous studies on the relationship between DNA methylation and UM covered many genes including tumor suppressor genes (TSGs), cyclin-dependent kinase genes, and other genes. Among them, the TSG genes such as RASSF1A and p16INK4a, which encodes a cyclin-dependent kinase inhibitor, are relatively well-studied genes. Specifically, a high percentage of promoter methylation of RASSF1A was observed in UM cell lines and/or patients with UM. Promoter methylation of RASSF1A was also associated with the development of metastasis. Similarly, a high percentage of promoter hypermethylation of p16INK4a was found in UM cell lines. DNA promoter methylation can control the expression of p16INK4a, which affect cell growth, migration, and invasion in UM. Many other genes might also be involved in the pathogenesis of UM such as the Ras and EF-hand domain containing (RASEF) gene, RAB31, hTERT, embryonal fyn-associated substrate, and deleted in split-hand/split-foot 1.</p><p><b>Conclusions</b>Our review reveals the complex mechanisms underlying the tumorigenesis of UM and highlights the great needs of future studies to discover more genes/5'-C-phosphate-G-3' sites contributing to the development/metastasis of UM and explore the mechanisms through which epigenetic changes exert their function in UM.</p>
Subject(s)
Humans , Cell Transformation, Neoplastic , Genetics , DNA Methylation , Genetics , Epigenesis, Genetic , Genetics , Melanoma , Genetics , Promoter Regions, Genetic , Genetics , Uveal Neoplasms , GeneticsABSTRACT
Objective: To explore the lipid regulating effect of fermentation product of Crataegi Fructus, Alismatis Rhizoma, and Cassiae Semen on hyperlipidemic rats. Methods: SD rats were fed with high fat diet and established as hyperlipidemia animal model, the subjects were divided into six groups: control group, model group, positive control group, fermentation product prevention group, red yeast rice group, and fermentation product treatment group. After four weeks continuous oral administration, the effect of different medicine samples on serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) of hyperlipidemic rats were observed to assess the regulation effect. Results: Four weeks' continuous oral administration could regulate the TC, TG, LDL-C levels significantly lower (P < 0.001) and HDL-C level significantly increased (P < 0.05) in the prevention group compared with the model group. After modeling, continuous administration for four weeks, compared with the levels before giving medicines, TC, TG, LDL-C levels of positive control group and fermentation product treatment group were significantly regulated lower (P < 0.05, 0.01) and HDL-C level significantly increased (P < 0.05, 0.01). while the only TC and LDL-C levels in red yeast rice group showed significant effect. Conclusion: Product of lipid-lowering traditional Chinese medicines (TCMs) treated by solid-state fermentation with Monascus purpureus could effectively inhibit the formation of foodborne hyperlipidemia, as well as control and regulate hyperlipidemia, and synergistic effect also appeared between ingredients from TCMs and lovastatin.
ABSTRACT
Objective: To obtain a new lipid-lowering product that combines the advantages of lipid-lowering Chinese materia medica (CMM) and statin drugs. Solid-state fermentation was studied using medicinal and edible CMM as media components, Lovastatin yielding monascus screened in our laboratory was used as strain and Lovastatin yielding was used as index. Methods: Solid-state fermentation was optimized by single factor and orthogonal test, qualitative and quantitative analysis was conducted of the product via TLC and HPLC. Results: The optimal fermentation conditions contained 100 g/solid medium in 500 mL flask bottling capacity, material thickness of 2.5 cm, 10 mL liquid seed of 48 h, 10% inoculation volume, incubating at 30℃, breaking up the medium on day 2, adding 24% sterile water on day 3, cooling to 25℃ and culturing for 18 d in total, and Lovastatin yielding was up to 5.127 mg/g. Fermentation product of CMM contained more components compared with that without medicines, Lovastatin yielding increased by 42.27%, but γ-aminobutyric acid yielding decreased by 17.89%. Contents of main active ingredients ursolic acid, 2,3-acetyl alisol-B, chrysophanol, and physcion were increased by 232.7%, 173.7%, 767.6%, and 888.4%. Conclusion: Active ingredients of hawthorn, alisma, and cassia are released into the products after fermentation and contents of lipid-lowering active ingredients were improved significantly, new active ingredients are also noticed. Therefore, the fermentation process of lipid-lowering medicines obtained in this experimental study has some practical values.