Construction of a Colorectal Cancer Prognostic Risk Model and Screening of Prognostic Risk Genes Using Machine-Learning Algorithms.

This study is aimed at constructing a prognostic risk model for colorectal cancer (CRC) using machine-learning algorithms to provide accurate staging and screening of credible prognostic risk genes. We extracted CRC data from GSE126092 and GSE156355 of the Gene Expression Omnibus (GEO) database and datasets from TCGA to analyze the differentially expressed genes (DEGs) using bioinformatics analysis. Among the 330 shared DEGs related to CRC prognosis, we divided the analysis period into different phases and applied univariate COX regression, LASSO, and multivariate COX regression analysis. GO analysis and KEGG analysis revealed that the functions of these DEGs were primarily focused on cell cycle, DNA replication, cell mitosis, and other related functions, and this confirmed our results from a biological perspective. Finally, a prognostic risk model for CRC based on the CHGA, CLU, PLK1, AXIN2, NR3C2, IL17RB, GCG, and AJUBA genes was constructed, and the risk score enabled us to predict the prognosis for CRC. To obtain a comprehensive and accurate model, we used both internal and external evaluations, and the model was able to correctly differentiate patients with CRC into a high-risk group with poor prognosis and a low-risk group with good prognosis. The AUC values of the 3-, 5-, and 10-year survival ROC curves were 0.715, 0.721, and 0.777, respectively, according to the internal evaluation, and the AUC values were 0.606, 0.698, and 0.608, respectively, for the external evaluation using GSE39582 from the GEO database. We determined that CLU, PLK1, and IL17RB could be considered to be independent prognostic factors for CRC with significantly different expression (P < 0.05). Using machine-learning methods, a prognostic risk model comprised of eight genes was constructed. Not only does this model provide improved treatment guidance, but it also provides a novel perspective for analyzing survival conditions at a deeper biological level.

Nanostructure Nickel-Based Selenides as Cathode Materials for Hybrid Battery-Supercapacitors.

Supercapacitors (SCs) have attracted many attentions and already became part of some high-power derived devices such as Tesla's electric cars because of their higher power density. Among all types of electrical energy storage devices, battery-supercapacitors are the most promising for superior performance characteristics, including short charging time, high power density, safety, easy fabrication procedures, and long operational life. An SC usually consists of two foremost components, namely electrode materials, and electrolyte. The selection of appropriate electrode materials with rational nanostructured designs have resulted in improved electrochemical properties for high performance and has reduced the cost of SCs. In this review, we mainly spotlight the nickel-based selenides nanostructured which applied as high-performance cathode materials for SCs. Different nickel-based selenides materials are highlighted in various categories, such as nickel-cobalt-based bimetallic chalcogenides and nickel-M based selenides. Also, we mentioned material modification for this material type. Finally, the designing strategy and future improvements on nickel-based selenides materials for the application of SCs are also discussed.

A solar-thermal energy harvesting scheme: enhanced heat capacity of molten HITEC salt mixed with Sn/SiO(x) core-shell nanoparticles.

We demonstrated enhanced solar-thermal storage by releasing the latent heat of Sn/SiO(x) core-shell nanoparticles (NPs) embedded in a eutectic salt. The microstructures and chemical compositions of Sn/SiO(x) core-shell NPs were characterized. In situ heating XRD provides dynamic crystalline information about the Sn/SiO(x) core-shell NPs during cyclic heating processes. The latent heat of ∼29 J g(-1) for Sn/SiO(x) core-shell NPs was measured, and 30% enhanced heat capacity was achieved from 1.57 to 2.03 J g(-1) K(-1) for the HITEC solar salt without and with, respectively, a mixture of 5% Sn/SiO(x) core-shell NPs. In addition, an endurance cycle test was performed to prove a stable operation in practical applications. The approach provides a method to enhance energy storage in solar-thermal power plants.

ZNF580, a novel C2H2 zinc-finger transcription factor, interacts with the TGF-ß signal molecule Smad2.

ZNF580 (gene ID 51157), a novel gene encoding a C2H2 (Cys2-His2) zinc-finger transcription factor, may be involved in the maintenance of vascular endothelium homoeostasis. To investigate the physiological role of the transcription factor ZNF580, we screened human foetal brain cDNA library with a yeast two-hybrid system and identified 14 proteins that interact with ZNF580. The interaction between ZNF580 and Smad2 was confirmed by co-immunoprecipitation. Co-localization between endogenous ZNF580 and Smad2 was mainly found in the nuclei of EA.hy926 endothelial cells with immunofluorescence and confocal microscopy. Our results suggest that ZNF580 is a binding partner of Smad2 and is involved in the signal transduction of the TGF-ß (transforming growth factor-ß) signalling pathway, which provides a basis for additional research to investigate the role of ZNF580 in the maintenance of vascular endothelium homoeostasis and the onset of atherosclerotic diseases.

Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growth.

Recent studies revealed the potential of Na(+)/K(+)-ATPase as a target for anticancer therapy and showed additional modes of action of cardiotonic steroids (CSs), a diverse family of naturally derived compounds, as inhibitors of Na(+)/K(+)-ATPase. The results from epidemiological studies showed significantly lower mortality rates in cancer patients receiving CSs, which sparked interest in the anticancer properties of these drugs. The present study was designed to investigate the anticancer effect of CSs (ouabain or cinobufagin) and to elucidate the molecular mechanisms of CS activity in hepatoma cell lines (HepG2 and SMMC-7721). Ouabain and cinobufagin significantly inhibited cell proliferation by attenuating the phosphorylation of extracellular regulated kinase (ERK) and down-regulating the expression of C-myc. These CSs also induced cell apoptosis by increasing the concentration of intracellular free calcium ([Ca(2+)](i)) and induced S phase cell cycle arrest by down-regulating the expression of Cyclin A, cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) as well as up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21(CIP1)). Overexpression of ERK reversed the antiproliferation effect of ouabain or cinobufagin in HepG2 and SMMC-7721 cells. Currently, the first generation of CS-based anticancer drugs (UNBS1450 and Anvirzel) are in Phase I clinical trials. These data clearly support their potential use as cancer therapies.

[Effect of Na(+)/K(+)-ATPase alpha1 siRNA and ouabain upon cell cycle in human hepatoma HepG2 cell and its mechanism].

OBJECTIVE: To investigate the in vitro anti-cancer effects of ouabain combined Na(+)/K(+)-ATPase alpha1 siRNA upon HepG2 cells and its molecular mechanism. METHODS: The Na(+)/K(+)-ATPase alpha1 subunit expressions of human hepatoma tissue, normal liver tissue and human hepatoma cell lines (HepG2, SMC7721 and Bel7402) were determined. The cells received different treatments (0.03 micromol/L siRNA, 0.1 micromol/L ouabain and combination). The proliferation of HepG2 was observed by CCK-8 assay. The activity of Na(+)/K(+)-ATPase was measured. The HepG2 cell cycle distribution was detected by flow cytometry. The mRNA and protein levels of Na(+)/K(+)-ATPase alpha1 subunit, MAPK1, Cyclin A, CDK2, PCNA and P21WAF1 were detected by quantitative RT-PCR and Western blot. RESULTS: The gray value Na(+)/K(+)-ATPase alpha1 subunit in hepatoma tissue was 174.74 +/- 16.77 and 65.31 +/- 7.88 respectively in normal liver tissue. The Na(+)/K(+)-ATPase alpha1 subunit expression of hepatoma tissue was significantly higher than normal liver tissue(P < 0.05).The Na(+)/K(+)-ATPase alpha1 subunit expression level of HepG2 was higher than that in SMMC-7721 and Bel-7402 cells. The CCK-8 experiments demonstrated that siRNA, ouabain and combination could inhibit the HepG2 proliferation, and the combination group was different from the ouabain or siRNA group (P < 0.05). The 24, 48 and 72 h inhibitory rates of 0.03 micromol/L siRNA, 0.1 micromol/L ouabain and combination group were (17.4%, 20.3%, 24.3%), (37.5%, 44.3%, 51.2%) and (52.3%, 70.2%, 88.2%) respectively. The activity of Na(+)/K(+)-ATPase decreased in siRNA, ouabain and combination group. The S phase proportion of ouabain and combination group increased from 24.2% to 66.5% and 75.2% respectively. The 0.1 micromol/L ouabain and combination group could down-regulate the expression of Na(+)/K(+)-ATPsae alpha1, MAPK1, Cyclin A, CDK2, PCNA and up-regulate the expression of P21WAF1 in HepG2 cell. CONCLUSION: The Na(+)/K(+)-ATPase alpha1 siRNA combined ouabain inhibits the proliferation of HepG2 cells by decreasing the expression of MAPK1 and induces the cell cycle S arrest by decreasing the production of Cyclin A/CDK2/PCNA complex and increasing the expression of P21(WAF1).

Targeting the Na(+)/K(+)-ATPase alpha1 subunit of hepatoma HepG2 cell line to induce apoptosis and cell cycle arresting.

Recent research has shown that the Na(+)/K(+)-ATPase alpha1 subunit is a novel anti-cancer target, which plays pivotal roles in malignant cell ion transport, metabolism, migration and signal transduction. The purpose of the present study was to investigate the anti-cancer effects of ouabain and Na(+)/K(+)-ATPase alpha1 small interfering ribonucleic acid (siRNA) on HepG2 cell proliferation, apoptosis and cell cycle, and to explore the molecular mechanisms. The expression of Na(+)/K(+)-ATPase alpha1 subunit in human hepatocellular carcinoma (HCC), normal liver tissues and human HCC line (HepG2, SMMC-7721 and Bel-7402) has been investigated. Using the ouabain and Na(+)/K(+)-ATPase alpha1 subunit siRNA, which target the Na(+)/K(+)-ATPase, we have evaluated the effects of inhibiting Na(+)/K(+)-ATPase alpha1 in human HepG2 cells with respect to cell proliferation, morphology, cell cycle, impact on intracellular Ca2++, reactive oxygen species (ROS) concentration, and correlated gene expression level on messenger ribonucleic acid (mRNA) and protein. Our data showed that the expression Na(+)/K(+)-ATPase alpha1 subunit in HCC tissues is higher than that in normal liver tissues. Ouabain and Na(+)/K(+)-ATPase alpha1 siRNA could inhibit HepG2 cell proliferation. Ouabain could induce HepG2 cell apoptosis and generate S phase arrest, and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated, and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A (P21(CIP1)). We believe that targeting of the Na(+)/K(+)-ATPase alpha1 subunit in human HCC cells could provide new sight into the treatment of HCC.

[Analyzing anti-cancer action mechanisms of dihydroartemisinin using gene chip].

OBJECTIVE: To understand the action mechanisms of artesunate on inhibiting leukaemia cell line K562 on the molecular level. METHOD: The gene chip was used to detect the expression panel of genes of leukaemia cell line K562 treated by dihydroartemisinin. K562 cells were treated with 1 x 10(-5), 4 x 10(-5), 16 x 10(-5), 64 x 10(-5), 256 x 10(-5) mol x L(-1) dihydroartemisinin for 24 h, and then studied the modality changes by invert microscope. The morphological changes of the nucleons were observed by Hoechst33342/PI staining. The cell cycle were examined by flow cytometry analysis (FCM). Total RNA samples were obtained by TRIzol and were reverse transcribed to the cDNA. The cDNA samples were hybridized to our gene chips. Hybridization signal were collected and analyzed following scanning by Gene Pix 4100A. RESULT: The numbers of drift cells were increased and the density of cells was decreased under invert microscope after K562 cells were treated with dihydroartemisinin for 24 h. Morphological changes of cell apoptosis such as karyopyknosis and conglomeration were observed by Hoechst 33342/PI staining. Flow cytometric analysis showed that cells were arrested in G2 phase. There were 13 differentially expressed genes identified. Hybridization analysis showed up-regulation of chk1 and down-regulation of PCNA, cyclinB1, cyclinD1, cyclinE1, cdk4, cdk2, E2F1, DNA-PK, DNA-Topo I, mcl-1, jNK, VEGF in the dihydroartemisinin-treated K562 cells. CONCLUSION: Dihydroartemisinin can Inhibit the leukaemia cell line K562 and exert its anti-cancer effect by altering the expression of these genes involved in cell cycle; dihydroartemisinin may act via apoptosis pathway.

[The role of ouabain in cell death of vascular endothelial cells ECV304 and the changes of expression of Na+, K(+)-ATPase alpha1, beta1-subunit].

AIM: To study the effect of Na+, K(+)-ATPase inhibition by ouabain on growth and death of vascular endothelial cells ECV304 and involved mechanisms. METHODS: Growth inhibition of ouabain on ECV304 cells was analyzed using MTT assay. The feature of cell death was studied by Hoechst 33342/PI staining, transmission electron microscopy and DNA agarose gel electrophoresis in ECV304 cells treated with ouabain. The mRNA expression of Na+, K(+)-ATPase alpha1, beta1-subunit was examined by reverse transcription PCR (RT-PCR). RESULTS: Ouabain inhibited the growth of ECV304 cells in a dose and time-dependent manner. 10 micromol/L ouabain treated for 24 hours could stimulate the necrosis of ECV304 cells; When treated with 0.1 micromol/L ouabain for 24-48 hours, the cells showed obviously defluxion, the loss of cell-cell contacts, nuclear chromatin condensation, chromatin margination and DNA fragmentation. Na+, K(+)-ATPase alpha1-subunit mRNA expression was significantly up-regulated in ECV304 cells treated with ouabain while the beta1-subunit expression conversely showed a significant decrease. CONCLUSION: Ouabain could up-regulate Na+, K(+)-ATPase alpha1-Subunit expression and reduce beta1-Subunit expression which mediated signal transduction and decreased cell-cell adhesions and induced ECV304 cells death.

[Inducement effect of 9-cis retinoic acid on cell cycle arrest and apoptosis of gastric carcinoma cell line MGC803 and its mechanism].

BACKGROUND & OBJECTIVE: Antitumor effect of 9-cis retinoic acid (9-cis RA) on gastric carcinoma is unclear yet. This study was to explore the inducement effect of 9-cis RA on cell cycle arrest and apoptosis of gastric carcinoma cell line MGC803 and its mechanism. METHODS: The expression of RXRalpha, Cyclin D1, and CDK4 in MGC803 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). Cell cycle was detected by flow cytometry. The growth inhibition was analyzed by MTT assay. The apoptosis was detected by agarose gel electrophoresis and Hoechst33342/PI staining. The expression of apoptosis-associated gene Bcl-2 was detected by SP immunocytochemistry. RESULTS: When treated with 0.1-10 micromol/L 9-cis RA for 96 h, the proliferation of MGC803 cells was significantly inhibited. The proportion of MGC803 cells at G1 phase was significantly increased when treated with 10 micromol/L 9-cis RA for 48, 72, and 96 h, and showed an apparent G1 phase arrest. When treated with 9-cis RA for 72 h, typical apoptotic changes, such as chromatin condensation and DNA ladder, were observed in MGC803 cells. The expression of Bcl-2 was significantly decreased in MGC803 cells when treated with 10 micromol/L 9-cis RA for 48 h. RXRalpha expression was at a low level in MGC803 cells and up-regulated when treated with 10 micromol/L 9-cis RA for 48 h (P<0.01). The expression of Cyclin D1 and CDK4 in MGC803 cells was both significantly down-regulated when treated with 10 micromol/L 9-cis RA for 96 h (P<0.01). CONCLUSION: 9-Cis RA could induce G1 phase arrest and apoptosis in MGC803 cells through down-regulating the expression of cell cycle factors Cyclin D1 and CDK4.