Circ ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 increases the stability of G9a and ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 messenger RNA through recruiting eukaryotic translation initiation factor 4A3, transcriptionally inhibiting PDZ and homeobox protein domain protein 1, and promotes the metastasis of hepatocellular carcinoma.

BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.

Comparison of narrow-band imaging and confocal laser endomicroscopy for the detection of neoplasia in Barrett's esophagus: A meta-analysis.

AIMS: Barrett's esophagus (BE) predisposes to the development of esophageal neoplasia, including high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). A systematic literature review and meta-analysis were performed to assess the accuracy of within-patient comparisons of narrow band imaging (NBI) and confocal laser endomicroscopy (CLE) for diagnosis of HGD/EAC in patients with BE. METHODS: The following databases were examined up to April 2016 without language restriction: PubMed, Embase, Medline, Web of Science and the Cochrane Library. The QUADAS-2 tool for assessing the quality of included studies was used. The meta-analysis included pooled additional detection rate (ADR), diagnostic accuracy, and 95% confidence intervals (CI). The I2 and Q-test were used to determine study heterogeneity. RESULTS: Five studies involving 251 patients, reported within-patient comparisons of NBI and CLE, were eligible for meta-analysis. Compared with NBI, pooled ADR of CLE for per-lesion detection of neoplasia in patients with BE was 19.3% (95% CI: 0.05-0.33, I2=74.6%). The pooled sensitivity of NBI was 62.8% (95% CI: 0.56-0.69, I2=94.6%), which was lower (not significantly) than that of CLE (72.3%, 95% CI: 0.66-0.78, I2=89.3%). The pooled specificity of NBI and CLE were similar [85.3% (95% CI: 0.84-0.87, I2=92.1%) vs 83.8% (95% CI: 0.82-0.85, I2=96.8%)]. CONCLUSIONS: When compared with NBI, CLE significantly increased the per-lesion detection rate of esophageal neoplasia, HGD, and EAC in BE patients. Whether CLE is superior to NBI in neoplasia detection at per-patient level needs to be further investigated.

Development and Validation of a Risk Score for Prediction of Acute Kidney Injury in Patients With Acute Decompensated Heart Failure: A Prospective Cohort Study in China.

BACKGROUND: Although several risk factors for acute kidney injury (AKI) have been identified, early detection of AKI in acute decompensated heart failure patients remains a challenge. The aim of this study was to develop and validate a risk score for early prediction of AKI in acute decompensated heart failure patients. METHODS AND RESULTS: A total of 676 consecutive acute decompensated heart failure participants were prospectively enrolled from 6 regional central hospitals. Data from 507 participants were analyzed. Participants from 4 of the 6 hospitals (n=321) were used to develop a risk score and conduct internal validation. External validation of the developed risk score was conducted in participants from the other 2 hospitals (n=186). Sequential logistic regression was used to develop and validate the risk score. The c statistic and calibration plot were used to assess the discrimination and calibration of the proposed risk score. The overall occurrence of AKI was 33.1% (168/507). The risk score, ranging from 0 to 55, demonstrated good discriminative power with an optimism-corrected c statistic of 0.859. Similar results were obtained from external validation with c statistic of 0.847 (95% CI 0.819-0.927). The risk score had good calibration with no apparent over- or under-prediction observed from calibration plots. CONCLUSIONS: The novel risk score is a simple and accurate tool that can help clinicians assess the risk of AKI in acute decompensated heart failure patients, which in turn helps them plan and initiate the most appropriate disease management for patients in time.