Differential hypermethylation of the VTRNA2-1 promoter in hepatocellular carcinoma as a prognostic factor: Tumor marker prognostic study.

BACKGROUND: Vault RNA 2-1 (VTRNA2-1, also called nc886) is a 108-nucleotide noncoding transcript that is epigenetically controlled via 18 CpG dinucleotide modifications of its promoter, and can exert either tumor suppressor or oncogenic functions depending on cell types of cancers. In hepatocellular carcinoma (HCC), the role of VTRNA2-1 in prognosis of patients remains unexplored. Here, we analysed the methylation status of the VTRNA2-1 promoter and its correlation with clinical parameters in patients with HCC. PATIENTS AND METHODS: A total of 92 patients with HCC were enrolled, genomic DNA of tumor versus normal tissues were extracted and bisulfite modified. VTRNA2-1 promoter regions chr5: 135416381 (cg06536614), 135416388, 135416394 (cg26328633), and 135416398 (cg25340688) were PCR amplified and pyrosequenced. The methylation status of VTRNA2-1 in patients was further analysed with other clinical parameters via univariate and multivariate analysis. RESULTS: The differential hypermethylation status (tumor- normal) of the VTRNA2-1 promoter in HCC correlated well with the presence of large tumor size (p = 0.001), pathological vascular invasion (p = 0.036), tumor recurrence (p = 0.007) and more advanced tumor stage (stage III AJCC) in patients (p = 0.03). In addition, the methylation of the VTRNA2-1 promoter increased in stage III HCC tumor compared with stage I & II tumor (64.7% versus 36.0%, p = 0.030). Furthermore, the differential hypermethylation status of the VTRNA2-1 promoter was an independent factor for patient outcome after partial hepatectomy using multivariate Cox regression analysis (p = 0.011, HR = 2.305). Using another public dataset (GSE89852), we found that the differential hypermethylation of the VTRNA2-1 promoter was also significantly associated with tumor recurrence. CONCLUSIONS: Patients had unfavourable outcomes when the VTRNA2-1 promoter was differentially hypermethylated in tumor tissues compared to its adjacent normal tissues. These findings suggest that such patients should receive intensive follow-up care or possible adjuvant therapy after liver resection.

Real-Time Observation of Anion Reaction in High Performance Al Ion Batteries.

Recently, aluminum ion batteries (AIBs) have attracted great attention across the globe by virtue of their massive gravimetric and volumetric capacities in addition to their high abundance. Though carbon derivatives are excellent cathodes for AIBs, there is much room for further development. In this study, flexuous graphite (FG) was synthesized by a simple thermal shock treatment, and for the first time, an Al/FG battery was applied as a cathode for AIBs to reveal the real-time intercalation of AlCl4- into FG with high flexibility by using in-situ scanning electron microscope (SEM) measurements exclusively. Similarly, in-situ X-ray diffraction (XRD) and in-situ Raman techniques have been used to understand the anomalous electrochemical behavior of FG. It was found that FG adopts a unique integrated intercalation-adsorption mechanism where it follows an intercalation mechanism potential above 1.5 V and an adsorption mechanism potential below 1.5 V. This unique integrated intercalation-adsorption mechanism allows FG to exhibit superior properties, like high capacity (≥140 mAh/g), remarkable long-term stability (over 8000 cycles), excellent rate retention (93 mAh/g at 7.5 A/g), and extremely rapid charging and slow discharging.

A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: a pilot study.

Background: Sepsis is a syndrome characterized by a constellation of clinical manifestations and a significantly high mortality rate in the surgical intensive care unit (ICU). It is frequently complicated by acute kidney injury (AKI), which, in turn, increases the risk of mortality. Therefore, it is of paramount importance to identify those septic patients at risk for the development of AKI and mortality. The objective of this pilot study was to evaluate several different biomarkers, including NGAL, calprotectin, KIM-1, cystatin C, and GDF-15, along with SOFA scores, in predicting the development of septic AKI and associated in-hospital mortality in critically ill surgical patients. Methods: Patients admitted to the surgical ICU were prospectively enrolled, having given signed informed consent. Their blood and urine samples were obtained and subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of various novel biomarkers. The clinical data and survival outcome were recorded and analyzed. Results: A total of 33 patients were enrolled in the study. Most patients received surgery prior to ICU admission, with abdominal surgery being the most common type of procedure (27 patients (81.8%)). In the study, 22 patients had a diagnosis of sepsis with varying degrees of AKI, while the remaining 11 were free of sepsis. Statistical analysis demonstrated that in patients with septic AKI versus those without, the following were significantly higher: serum NGAL (447.5 ± 35.7 ng/mL vs. 256.5 ± 31.8 ng/mL, P value 0.001), calprotectin (1030.3 ± 298.6 pg/mL vs. 248.1 ± 210.7 pg/mL, P value 0.049), urinary NGAL (434.2 ± 31.5 ng/mL vs. 208.3 ± 39.5 ng/mL, P value < 0.001), and SOFA score (11.5 ± 1.2 vs. 4.4 ± 0.5, P value < 0.001). On the other hand, serum NGAL (428.2 ± 32.3 ng/mL vs. 300.4 ± 44.3 ng/mL, P value 0.029) and urinary NGAL (422.3 ± 33.7 ng/mL vs. 230.8 ± 42.2 ng/mL, P value 0.001), together with SOFA scores (10.6 ± 1.4 vs. 5.6 ± 0.8, P value 0.003), were statistically higher in cases of in-hospital mortality. A combination of serum NGAL, urinary NGAL, and SOFA scores could predict in-hospital mortality with an AUROC of 0.911. Conclusions: This pilot study demonstrated a promising panel that allows an early diagnosis, high sensitivity, and specificity and a prognostic value for septic AKI and in-hospital mortality in surgical ICU. Further study is warranted to validate our findings.

Establishment of two basal-like breast cancer cell lines with extremely low tumorigenicity from Taiwanese premenopausal women.

The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements. Cells were further enriched by positive selection with CD326 (epithelial cell adhesion molecule; EpCAM)-coated micro-magnetic beads. Two breast cancer cell lines derived from premenopausal women were successfully established by this method, and named Chang-Gung Breast Cancer 01 (CGBC 01) and 02 (CGBC 02). These two cell lines had a similar phenotype with weak expression of estrogen receptor (ER), progesterone receptor (PR), and without amplification of receptor tyrosine protein kinase erbB-2 (HER2/neu). Genome-wide Single Nucleotide Polymorphism (SNP) array showed multiple copy number alterations in both cell lines. Based on gene expression profiles, CGBC 01 and 02 were clustered into basal-like subtype with reference to the breast cancer cell line gene expression database. The tumorigenicity of both cell lines was extremely low in both anchorage-independence assay and transplantation into the mammary fat pads of nude mice. CGBC 01 and CGBC 02 are low tumorigenic breast cancer cell lines, established from Han-Chinese premenopausal breast cancer patients, which serve as in vitro models in studying the biological features of Asian breast cancer.

Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data.

AIM: To identify chromosomal copy number aberrations (CNAs) in early-stage hepatocellular carcinoma (HCC) and analyze whether they are correlated with patient prognosis. METHODS: One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded (FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosin-stained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix OncoScan platform to assess CNAs and loss of heterozygosity (LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage I/II HCC were enrolled to analyze gene expression and to correlate findings with the OncoScan data. RESULTS: Copy number amplifications occurred at chromosomes 1q21.1-q44 and 8q12.3-24.3 and deletions were found at 4q13.1-q35.2, 8p 23.2-21.1, 16q23.3-24.3, and 17p13.3-12, while LOH commonly occurred at 1p32.3, 3p21.31, 8p23.2-21.1, 16q22.1-24.3, and 17p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change (≥ 60%) was an independent factor for worse prognosis in early-stage HCC (P = 0.031). Among the 875 genes in the OncoScan GeneChip, six were independent predictors of worse disease-free survival, of which three were amplified (MYC, ELAC2, and SYK) and three were deleted (GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs (P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes. CONCLUSION: Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.

Exendin-4 treatment expands graft beta-cell mass in diabetic mice transplanted with a marginal number of fresh islets.

Exendin-4 stimulates insulin secretion, suppresses glucagons secretion, increases beta-cell replication and neogenesis, and reduces beta-cell apoptosis. However, it has been shown that posttransplant exendin-4 treatment did not improve glucose homeostasis in diabetic mice transplanted with a large number of freshly isolated islets. The aim of this study was to test if exendin-4 is beneficial for hyperglycemic recipients with a marginal number of fresh islets. We transplanted 150 C57BL/6 mouse islets under the kidney capsule of inbred streptozotocin-diabetic mice, and then treated the recipients with and without exendin-4 for 6 weeks. Before and after transplantation, recipients' blood glucose, body weight, and intraperitoneal glucose tolerance test were measured. At 6 weeks, the grafts were removed to determine beta-cell mass. Blood glucose levels in both groups decreased progressively after transplantation, and the exendin-4-treated group had had lower blood glucose than controls since day 3. By 6 weeks, euglycemia was achieved more in mice treated with exendin-4 than in controls (100% vs. 62.5%, p = 0.018). The time to obtain normoglycemia was shorter in the exendin-4-treated group than in controls (12 +/- 8 vs. 29 +/- 13 days, p < 0.001). Blood glucose at 6 weeks was 123 +/- 18 and 170 +/- 62 mg/dl in the exendin-4-treated group and controls, respectively (p = 0.008). Additionally, the exendin-4-treated group had better glucose tolerance than controls at 2 and 4 weeks (p <0.02). However, both groups exhibited increased body weight over time, and weight changes did not significantly differ between the two groups throughout the study period. At 6 weeks after transplantation, grafts in the exendin-4-treated group were more prominent and contained more insulin-stained cells than those of controls. They had 2.3-fold beta-cell mass of the graft compared with controls (0.30 +/- 0.11 vs. 0.13 +/- 0.03 mg, p = 0.012). These results indicate posttransplant exendin-4 treatment in the diabetic recipient with a marginal number of fresh islets expands graft beta-cell mass and improves transplantation outcome.

Basic dye decomposition kinetics in a photocatalytic slurry reactor.

Wastewater effluent from textile plants using various dyes is one of the major water pollutants to the environment. Traditional chemical, physical and biological processes for treating textile dye wastewaters have disadvantages such as high cost, energy waste and generating secondary pollution during the treatment process. The photocatalytic process using TiO2 semiconductor particles under UV light illumination has been shown to be potentially advantageous and applicable in the treatment of wastewater pollutants. In this study, the dye decomposition kinetics by nano-size TiO2 suspension at natural solution pH was experimentally studied by varying the agitation speed (50-200 rpm), TiO2 suspension concentration (0.25-1.71 g/L), initial dye concentration (10-50 ppm), temperature (10-50 degrees C), and UV power intensity (0-96 W). The experimental results show the agitation speed, varying from 50 to 200 rpm, has a slight influence on the dye decomposition rate and the pH history; the dye decomposition rate increases with the TiO2 suspension concentration up to 0.98 g/L, then decrease with increasing TiO2 suspension concentration; the initial dye decomposition rate increases with the initial dye concentration up to a certain value depending upon the temperature, then decreases with increasing initial dye concentration; the dye decomposition rate increases with the UV power intensity up to 64 W to reach a plateau. Kinetic models have been developed to fit the experimental kinetic data well.

Interleukin-1 system messenger ribonucleic acid and protein expression in human fallopian tube may be associated with ectopic pregnancy.

OBJECTIVE: To investigate the interleukin-1 (IL-1) system mRNA and protein expression in human fallopian tubes with ectopic pregnancies. DESIGN: A controlled study. SETTING: Clinical and academic research setting in a university medical center. PATIENT(S): Women undergoing salpingectomy for fallopian tube with ectopic pregnancy and women undergoing tubal ligation. INTERVENTION(S): Paired segments of human fallopian tubes containing an ectopic pregnancy and parafallopian tube segments adjacent to the ectopic pregnancy were collected from five women undergoing laparoscopic salpingectomy. Segments of fallopian tubes from four women undergoing tubal ligation were used as control tissues. Quantitative competitive polymerase chain reaction (QC-PCR) and immunohistochemistry were performed. MAIN OUTCOME MEASURE(S): The differences of IL-1 system mRNA and the ratio of IL-1beta to IL-1 receptor antagonist (IL-1ra) in both fallopian tubes with ectopic pregnancies and normal controls were analyzed. RESULT(S): A complete IL-1 system mRNA and protein expression was identified in both fallopian tubes with ectopic pregnancies and normal controls. As QC-PCR demonstrated, IL-1beta mRNA expression was decreased, and IL-1ra and IL-1 receptor type 1 were increased in fallopian tubes with ectopic pregnancies in comparison with normal control tubes. In para-ectopic tubes, IL-1 receptor type 1 mRNA was statistically significantly increased in comparison with normal controls. There was a lower ratio of IL-1beta to IL-1ra at mRNA in fallopian tubes with ectopic pregnancies. CONCLUSION(S): These results suggest that an inappropriate ratio of IL-1beta to IL-1ra and a higher expression of its receptor in fallopian tubes may possibly be implicated to the implantation of an ectopic pregnancy in the oviduct.