Casticin exerts anticarcinogenic activity in several types of cancers, including human hepatocellular carcinoma (HCC). The aim of the present study was to investigate the effects of casticin, which is derived from Fructus Viticis Simplicifoliae, on the self-renewal capacity of liver cancer stem cells (LCSCs) derived from the HCC MHCC97 cell line. The present study demonstrated that casticin significantly inhibited the proliferation of LCSCs from the MHCC97 cell line in a dose-dependent manner (P<0.05), the half maximal inhibitory concentration of the parental cells and LCSCs was 17.9 and 0.5 μmol/l, respectively. Furthermore, casticin reduced the sphere-forming capacity of LCSCs and downregulated β-catenin protein expression in a concentration-dependent manner. Lithium chloride, an agonist known to activate the Wnt/β-catenin signaling pathway, attenuated the casticin-induced downregulation of β-catenin protein expression and inhibited the self-renewal capacity. To the best of our knowledge, the present study is the first to demonstrate that casticin effectively eradicates LCSCs and β-catenin was identified as the potential target. Thus, casticin may offer a novel therapeutic approach for the treatment of HCC.

The authors describe a fluorescence polarization assay for HIV-DNA. It is based on the use of gold nanoparticles (AuNPs) modified with DNA dendritic macromolecules that act as signal amplifiers. In the presence of HIV-DNA, the AuNP-DNA dendritic macromolecules and fluorescently labeled DNA probe combine with HIV-DNA in a sandwich format to form a conjugate. This reaction slows down the rotational speed of the labeled DNA probe because of the increase of molecular weight and volume. This increases fluorescence polarization and the sensitivity of the system. The relative fluorescence polarization values increase linearly in the 150 pM to 6 nM HIV-DNA concentration range, with a 73 pM detection limit. The results show this amplification strategy to be most useful for ultrasensitive determination of oligonucleotides by means of fluorescence polarization. Graphical abstract Schematic of a novel fluorescence polarization assay for the HIV-DNA. Ultrasensitive detection is accomplished by using AuNP-DNA dendritic macromolecules as signal amplification factor.

BackgroundCell division cycle-associated protein 2 (CDCA2) is a member of cell cycle-related proteins. CDCA2 plays a role in the regulation of protein phosphatase 1(PP1) γ-dependent DNA damage response (DDR) and H3 phosphorylation. CDCA2 promotes the tumorigenesis and development of several types of cancers by promoting the proliferation of tumor cells. However, the relationship between CDCA2 expression and the clinicopathological characteristics of hepatocellular carcinoma (HCC) is unknown.MethodsGene expression information and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The expression of CDCA2 and its correlation to clinical characteristics in HCC were analyzed. The expression level of CDCA2 was validated in HCC cell lines. The relationship between CDCA2 expression and the survival of patients with HCC was analyzed by using Kaplan–Meier method. The prognostic value of CDCA2 in HCC was estimated by Cox regression analysis. The expression difference of CDCA2 between HCC and normal tissues and its correlation to survival were verified in independent datasets. Gene set enrichment analysis (GSEA) was used to screen the CDCA2-related signaling pathways.ResultsCell division cycle-associated protein 2 expression was upregulated in HCC tissues (p &lt; 0.001) and increased CDCA2 was correlated to increased T stage, pathologic stage, histologic grade, and alpha-fetoprotein (AFP) level (p &lt; 0.001). In addition, CDCA2 was overexpressed in HCC cell lines HepG2 and LM3. High CDCA2 expression level was associated with poor overall survival [hazard ratio (HR) = 1.69; 95% CI, 1.20–1.40, p = 0.003], disease specific survival (HR = 1.73; 95% CI, 1.11–2.71, p = 0.016), and progress free interval (HR = 1.74; 95% CI, 1.30–2.34, p &lt; 0.001). Overexpression of CDCA2 and its correlation to poor survival in HCC were verified in Gene Expression Omnibus (GEO) datasets and Kaplan–Meier plotter database. Increased CDCA2 expression was associated with upregulation of PD-L1 (Spearman's coefficient = 0.207, p &lt; 0.001), PD-L2 (Spearman coefficient's = 0.118, p &lt; 0.05), and CTLA4 (Spearman's coefficient = 0.355, p &lt; 0.001). GSEA showed that homologous recombination pathway, insulin signaling pathway, mitogen-activated protein kinase (MAPK) pathway, mismatch repair pathway, mechanistic target of rapamycin (mTOR) pathway, Notch pathway, T cell receptor pathway, toll like receptor pathway, and WNT pathway were enriched in CDCA2 high expression phenotype.ConclusionCell division cycle-associated protein 2 may serve as an independent biomarker for poor prognosis in HCC and increased CDCA2 expression was associated with upregulation of immune checkpoints.

To investigate the crack behaviour of rock or rock-like material in uniaxial loading, a series of numerical simulations were conducted on gypsum specimens containing a single flaw with different inclination angle (0 ∘ -90 ∘ ) and length (10 mm-30 mm). Based on the numerical simulations results, the effect of flaw length on peak strength, the CI stress, and the CD stress were investigated with different inclination angles. The results show that the peak strength decreased initially and then increased with increasing of the flaw angle. Meanwhile, the peak strength decreased gradually when the length of the preexisting flaw increased. When the inclination angle was 30 ∘ , 45 ∘ , and 60 ∘ , the reduction degree of peak strength increased with increasing of the flaw length. The CI stress and CD stress not only depend on the inclination angle but also depend on flaw length. Four types of crack were observed in numerical simulations. The present research facilitates increased understanding of crack behaviour of rock under different conditions.