Picropodophyllin

HBV X protein (HBx), the smallest open reading frame in the hepatitis B virus (HBV) genome, can promote hepatocellular carcinoma (HCC) tumorigenesis by activating the expression of multiple oncogenes through inducing epigenetic alterations and interacting with the underlying transcriptional machinery. HBV non-infected HepG2 and Huh7 cells were transfected with HBx expression plasmids. The transcriptional, protein expression, and secretion levels of IGF-1 were detected by RT-qPCR, western blot, and ELISA, respectively. ChIP-qPCR was used to analyze the binding proteins on the IGF-1 gene. A co-culture system of HCC and Treg cells was designed using Transwell chambers. IGF-1 mRNA, protein, and secretion levels were increased in HepG2 and Huh7 cells exogenously expressing HBx. HBx was able to enter the nucleus and interact with the enhancer region of the IGF-1 gene. Levels of WDR5 and H3K4me1, which bind to the enhancer region of the IGF-1 gene, were also increased in HepG2 and Huh7 cells ectopically expressing HBx. Knockdown of WDR5 counteracted the upregulation of IGF-1 mRNA and protein levels by HBx. In the cell co-culture system, HBx/IGF-1 signaling in HCC cells promoted Treg cells expansion, IL-10 secretion, and infiltration, which was blocked by the IGF-1R inhibitor picropodophyllin. HBx/WDR5 promoted IGF-1 transcription in HCC cells through enhancers. HBx could promote Treg cell recruitment, infiltration, and activity by enhancing IGF-1 expression. IGF-1/IGF-1R signaling plays an important role in the communication between HCC cells and Treg cells. Targeting WDR or IGF-1/IGF-1R would be beneficial for the treatment of HCC.

Lanzhou lily/Baihe (Lilium davidii var. unicolor) is recognized as a traditional medicinal plant in China and is consumed as an edible bulbous vegetable, known for its numerous health benefits.However, comprehensive studies on its chem. composition remain limited.Therefore, in this study, we employed ultra-high-performance liquid chromatog.-Q Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) to systematically analyze and identify the chem. constituents of Lanzhou lily.A total of 210 compounds were identified from Lanzhou lily, including 43 glycosides and carbohydrates, 39 phenylpropanoids, 30 terpenes, 21 flavonoids, 19 amino acids and derivatives, 11 fatty acyl,9 phenols, 7 organic acids and their derivatives, 5 carboxylic acids and their derivatives,4 pyridines and derivatives, 5 alkaloids,3 steroids compounds and other phytochems., of which 184 were reported for the first time in Lanzhou lily.These active ingredients support the nutritional benefits and medicinal properties of Lanzhou lily.This study provides insight into the chem. properties of Lanzhou lily and may help further research to identify the factors that lead to the health benefits of this plant.