9alpha,13alpha-Dihydroxylisopropylidenylisatisine A (1), which was derived from isatisine A (2) and possessed an unprecedented fused pentacyclic skeleton, was isolated from the leaves of Isatis indigotica Fort. The structure and relative configuration were elucidated on the basis of extensive NMR analyses and finally determined by single-crystal X-ray diffraction. Compound 1 showed moderate anti-HIV-1 activity with EC50 = 37.8 microM and SI = 7.98.
A new triterpenoid named alisol O ( 1) was isolated from the rhizomes of Alisma orientalis, together with six known compounds: alisol A 24-acetate ( 2), 25-anhydroalisol A ( 3), 13 beta,17 beta-epoxyalisol A ( 4), alisol B 23-acetate ( 5), alisol F ( 6), and alisol F 24-acetate ( 7). Based on 1D and 2D-NMR data (HMQC, HMBC, COSY, ROESY), the structure of the new compound was deduced to be 11-dehydroxy-12-dehydroalisol F-24-acetate ( 1). Compounds 2 - 7 exhibited inhibitory activity in vitro on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line with IC (50) values of 2.3, 11.0, 15.4, 14.3, 0.6 and 7.7 microM, and on HBV e antigen (HBeAg) secretion with IC (50) values of 498.1, 17.6, 41.0, 19.9, 8.5 and 5.1 microM, respectively.
Four new hasubanane-type alkaloids, periglaucines A-D (1-4), and three known alkaloids, norruffscine (5), (-)-8-oxotetrahydropalmatine (6), and (-)-8-oxocanadine (7), were isolated from the aerial parts of Pericampylus glaucus. Their structures were elucidated on the basis of extensive NMR and EIMS data, and that of periglaucine A (1) was confirmed by single-crystal X-ray diffraction. Alkaloids 1-4 inhibited hepatitis B virus (HBV) surface antigen (HBsAg) secretion in Hep G2.2.15 cells. (-)-8-Oxotetrahydropalmatine (6) possessed a high selectivity index (SI = 22.4) for HBsAg secretion of the Hep G2.2.15 cell line with an IC(50) value of 0.14 mM. Norruffscine (5) and (-)-8-oxotetrahydropalmatine (6) exhibited inhibitory activity against human immunodeficiency virus (HIV-1) with EC(50) values of 10.9 and 14.1 microM in C8166 cells (SI = 45.7 and 18.8), respectively.
Five new icetexane diterpenoids, namely, perovskatones B-D (1, 3, 4), 1α-hydroxybrussonol (2), and 1α-hydroxypisiferanol (5), were isolated from Perovskia atriplicifolia, together with a new natural product (6) and two known compounds, przewalskin E (7) and brussonol (8). The structures of the new compounds were elucidated by detailed analyses of their MS, IR, 1D, and 2D NMR data. Compounds 1-8 were assayed for their inhibitory hepatitis B virus activities in the HepG 2.2.15 cell line. The results suggested that compounds 1 and 2 possessed noticeable anti-hepatitis B virus activity in vitro, suppressing the replication of hepatitis B virus DNA with selectivity index values of 154.3 and 137.7, respectively.
Swerilactones H-K (1-4), which are four novel lactones with an unprecedented C29 skeleton, were isolated from Swertia mileensis (Qing-Ye-Dan), an endemic Chinese herb used for treating viral hepatitis. Their structures were determined by extensive spectroscopic and X-ray crystallographic diffraction analyses. Swerilactones H-K exhibit potent anti-hepatitis B virus activity against HBV DNA replication with IC(50) values ranging from 1.53 to 5.34 μM. For the first time, a plausible biogenetic pathway for swerilactones H-K, together with the previously reported swerilactones A-D is proposed. From a biogenetic point of view, swerilactones A-D are ascribed as secoiridoid dimers, and swerilactones H-K as secoiridoid trimers.
BACKGROUND
The circular RNA circ-PRKCI is an endogenous non-coding RNA that forms a covalently closed ring after reverse splicing, which plays a key role in the occurrence and development of multiple digestive system tumors.
AIM
To investigate the role and mechanism of circ-PRKCI in the occurrence and development of hepatocellular carcinoma (HCC).
METHODS
This study used real-time polymerase chain reaction to detect the expression of circ-PRKCI in tumor tissues, tumor adjacent tissues, and blood in patients with HCC and other digestive system tumor cells. A series of functional tests were performed to explore whether circ-PRKCI affects the growth of HCC cells and what is its mechanism in HCC. Meanwhile, fluorescence
in situ
hybridization was used to detect the subcellular localization of circ-PRKCI. Survival analysis was performed to predict the correlation between circ-PRKCI and the prognosis of HCC. Chi-square test and
t
-test were performed for statistical analyses.
RESULTS
The level of circ-PRKCI was significantly higher in HCC tissues than in tumor adjacent tissues, and in HCC cell lines than in cells lines of esophageal, liver, stomach, and colon cancers. A series of functional tests showed that circ-PRKCI substantially inhibited cell apoptosis and promoted cell invasion. It was found that circ-PRKCI can act as the sponge of miRNA-545 to reduce the expression of AKT3 protein. Moreover, the result of survival analysis showed that circ-PRKCI target gene
E2F7
can reduce liver cancer patients’ survival rate. And clinical data suggested that the distribution of circ-PRKCI rose with the depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, indicating that circ-PRKCI may affect the survival and prognosis of patients with HCC by regulating
E2E7
.
CONCLUSION
This study explores the role and mechanism of circ-PRKCI in HCC, which provides a new research direction and theoretical basis for the treatment of HCC.
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