Molecular subtypes based on DNA sensors predict prognosis and tumor immunophenotype in hepatocellular carcinoma.

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma.

BACKGROUND: Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphate phosphatase that played a role in regulating lipid metabolism and there is still blank in the clinico-pathological significance and functional roles of ACP6 in human cancers. No investigations have been conducted on ACP6 in hepatocellular carcinoma (HCC) up to date. METHODS: Herein, we appraised the clinico-pathological significance of ACP6 in HCC via organizing expression profiles from globally multi-center microarrays and RNA-seq datasets. The molecular basis of ACP6 in HCC was explored through multidimensional analysis. We also carried out in vitro and in vivo experiment on nude mice to investigate the effect of knocking down ACP6 expression on biological functions of HCC cells, and to evaluate the expression variance of ACP6 in xenograft of HCC tissues before and after the treatment of NC. RESULTS: ACP6 displayed significant overexpression in HCC samples (standard mean difference (SMD) = 0.69, 95% confidence interval (CI) = 0.56-0.83) and up-regulated ACP6 performed well in screening HCC samples from non-cancer liver samples. ACP6 expression was also remarkably correlated with clinical progression and worse overall survival of HCC patients. There were close links between ACP6 expression and immune cells including B cells, CD8 + T cells and naive CD4 + T cells. Co-expressed genes of ACP6 mainly participated in pathways including cytokine-cytokine receptor interaction, glucocorticoid receptor pathway and NABA proteoglycans. The proliferation and migration rate of HCC cells transfected with ACP6 siRNA was significantly suppressed compared with those transfected with negative control siRNA. ACP6 expression was significantly inhibited by nitidine chloride (NC) in xenograft HCC tissues. CONCLUSIONS: ACP6 expression may serve as novel clinical biomarker indicating the clinical development of HCC and ACP6 might be potential target of anti-cancer effect by NC in HCC.

Front-face synchronous fluorescence spectroscopy for rapid and non-destructive determination of free capsanthin, the predominant carotenoid in chili (Capsicum annuum L.) powders based on aggregation-induced emission.

Capsanthin is the major natural carotenoid pigment in red chili pepper possessing important bioactivity. Its conventional determination method is high performance liquid chromatography (HPLC) with complex and tedious sample pretreatment. In this study, synchronous front-face fluorescence spectroscopy (FFFS) was applied for the fast and non-invasive detection of free capsanthin in chili powders. Although capsanthin was only weak fluorescent in solution state, it showed strong fluorescence in two separated regions in front-face geometry which could also be clearly observed in chili powders. The mechanisms of these emissions are revealed to be aggregation-induced emission (AIE) and J-aggregate formation (JAF). The free capsanthin in 85 chili powder samples were determined by HPLC as in the range of 0.6-3.0 mg/g. The total synchronous FFFS spectra of these samples were scanned. Simple first-order models were built by partial least square regression (PLSR), and were validated by 5-fold cross-validation and external validation. The coefficients of determination (R2) were higher than 0.9, and the root mean square errors (RMSE) were less than 0.2 mg/g. The relative error of prediction (REP) was 9.9%, and the residual predictive deviation (RPD) was 3.7. The method was applied for the estimation of free capsanthin in several real-world samples with satisfactory analytical results. The average relative error to HPLC reference values was -11.8%.

Expression of Cell Division Cycle Protein 45 in Tissue Microarrays and the CDC45 Gene by Bioinformatics Analysis in Human Hepatocellular Carcinoma and Patient Outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) causes a heavy disease burden worldwide. Cell division cycle 45 (Cdc45) and its encoding gene (CDC45) have been studied for a long time, but their expression patterns and roles in liver carcinogenesis and advanced HCC deterioration are still incompletely understood. This study integrated tissue microarray and bioinformatics analyses to explore the expression and clinical value of CDC45 and Cdc45 in HCC. MATERIAL AND METHODS In HCC, the expression and relationships with clinic-pathological parameters of CDC45 and Cdc45 were investigated by integrating the RNA-sequencing data, downloaded from The Cancer Genome Atlas and Oncomine databases, and tissue microarray with immunohistochemistry staining. Co-expressed genes and genetic alterations of CDC45 separately obtained from Oncomine and cBioPortal databases were identified to shed light on the potential mechanisms of CDC45 in HCC. RESULTS CDC45 and Cdc45 were both overexpressed in HCC tissues, and the CDC45 level progressively increased from stage I to III. The survival outcomes of the group with high CDC45 expression were significantly worse compared with the group with low expression. Amplification and deep deletion were 2 major significant alteration types in HCC patients, and the outcomes were worse in patients with altered versus unaltered CDC45. NUDT1, E2F1, CCNE2, MCM5, and CENPM were identified as the most significantly co-expressed genes. CONCLUSIONS CDC45 and Cdc45 were both upregulated in HCC, and increased expression levels and genetic alternations of CDC45 were correlated with worse prognosis in HCC patients. CDC45 may promote HCC by co-expressing with NUDT1, E2F1, CCNE2, MCM5, and CENPM.

Improvement of the stabilities and antioxidant activities of polyphenols from the leaves of Chinese star anise (Illicium verum Hook. f.) using ß-cyclodextrin-based metal-organic frameworks.

BACKGROUND: Polyphenols extracted from plants are usually highly unstable and rapidly transformed into various reaction products during food and drug processing, thus limiting their applications. To improve the stability and solubility of polyphenols from the leaves of Chinese star anise (Illicium verum Hook. f.), and hence to expand their application to food and medicine, the extracted anise leaf polyphenols (ALPs) were microencapsulated using ß-cyclodextrin (ß-CD) and cyclodextrin-based metal-organic frameworks (ß-CD-MOFs). RESULTS: The optimum inclusion rate of ALP/ß-CD-MOFs was 97.80% at a core-wall ratio of 1:10. Meanwhile, the stabilities, solubilities and antioxidant activities of the polyphenols before and after inclusion were compared. The results showed both the stabilities and solubilities of ALP/ß-CD-MOFs were significantly improved compared with those of ALPs and ALP/ß-CD, suggesting the potential of ß-CD-MOFs as newer and better carriers than ß-CD for polyphenols in food industry applications. The free radical (including superoxide, hydroxyl and DPPH radicals) scavenging activities were also improved by microencapsulation. Superoxide radical scavenging reaction also showed slow-release property of ALP/ß-CD-MOFs. The formation of the inclusion complex was further confirmed using Fourier transform infrared spectral characterization. CONCLUSIONS: Microencapsulation with ß-CD-MOFs could expand the application scope of ALPs, and it is more effective than encapsulation with ß-CD. This is important for a better understanding and application of this useful traditional Chinese plant. As a new material with high efficiency and edibility, ß-CD-MOFs are not limited to the chemical field, but also have potential in new areas of food, medicine and healthcare products. © 2020 Society of Chemical Industry.

Investigation of miR-490-3p Expression in Hepatocellular Carcinoma Based on Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) and a Meta-Analysis of 749 Cases.

BACKGROUND miR-490-3p could play vital roles in multiple cancers. However, the role of miR-490-3p in hepatocellular carcinoma (HCC) remains uncertain. In this study, we sought to explore the underlying role of miR-490-3p in HCC. MATERIAL AND METHODS In this study, we explored the clinical role of miR-490-3p in HCC via quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and The Cancer Genome Atlas (TCGA) database. Then, a meta-analysis was performed to evaluate the expression trend and diagnostic value of miR-490-3p in HCC. Furthermore, 12 miRNA prediction algorithms were applied to predict the potential target genes of miR-490-3p. The differentially expressed genes in HCC in the Gene Expression Profiling Interactive Analysis (GEPIA) database were also selected. Additionally, bioinformatics analyses were utilized to investigate the possible functions and pathways of the target genes. RESULTS miR-490-3p was clearly down-regulated in HCC based on RT-qPCR (P=0.002). Consistent with the results of RT-qPCR, miR-490 was more highly expressed in normal liver tissue than in HCC (P<0.001). Additionally, the meta-analysis confirmed the results from RT-qPCR and TCGA. Furthermore, based on the prediction algorithms and GEPIA, a total of 113 genes were selected. According to the bioinformatics analyses, we found that the most remarkably enriched functional terms included protein transport, poly(A) RNA binding, and intracellular organelle part. Additionally, the miR-490-3p target genes were significantly related to the pathways in cancer. CONCLUSIONS We found that miR-490-3p is down-regulated in HCC and is related to genes that have potential tumoral functions. However, the exact mechanism should be confirmed by functional experiments.

[Clinical application of a method for evaluating von Willebrand factor cleaving protease activity].

OBJECTIVE: To establish a method for evaluating the activity of von Willebrand factor cleaving protease (vWF-cp) and evaluate its clinical application. METHODS: Purified von Willebrand factor polymer was isolated by gel filtration from human fresh-frozen plasma as the enzyme substrate. SDS-PAGE, Western blotting, and luminographic detection were used to evaluate vWF-cp activity of 60 healthy adults, 28 patients with cerebral infarction (CI) and 7 with thrombotic thrombocytopenic purpura (TTP). RESULTS: In the subjects involved, the method for evaluating vWF-cp activity had intra- and inter-batch coefficient of variation(CV) of 4.81% (n=8) and 8.63% (n=6), respectively. According to this method, the plasma vWF-cp activity in the 60 healthy adults was significantly higher than that in the CI patients [(86.53-/+17.49)% vs (77.15-/+16.72)%, P<0.05]. In TTP patients before plasma replacement, the vWF-cp activity was (9.06-/+7.17)% and increased significantly to (47.00-/+6.27)% 24 h after plasma replacement, respectively, but still significantly lower than that of healthy adults (P<0.01), whereas in the convalescent stage, the activity approached the normal level [(83.18-/+8.83)%, P>0.05]. CONCLUSIONS: According to the described method, which allows accurate vWF-cp activity measurement with good sensitivity, specificity and reproducibility, vWF-cp activity is lower in CI patients and even more so in TTP patients than that of healthy adults. Plasma replacement can effectively increase the vWF-cp activity in TTP patients.