No abstract

Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1 and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies. A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC. http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg .

Rationale: Aberrant bronchial epithelium-fibroblast communication is essential for the airway remodeling that contributes to chronic obstructive pulmonary disease (COPD). Exosomes have emerged as novel mediators of intercellular communication, but their role in cigarette smoke (CS)-induced COPD is unknown. Here, we investigated the role of exosomal miR-21 in the dysfunctional epithelium-fibroblast cross-talk caused by CS.Methods: Normal or CS extract (CSE)-treated human bronchial epithelial (HBE) cells were co-cultured with bronchial fibroblasts (MRC-5 cells). Exosomes were obtained from culture media or serum by use of commercial kits. The size distribution and concentration of exosomes were analyzed by nanoparticle tracking analysis using a ZetaView particle tracker from ParticleMetrix. Inhibition of miR-21 levels by tail vein injection of antagomir-21 into mice exposed to CS was used to demonstrate the role of miR-21 in airway remodeling leading to COPD in animals.Results: For MRC-5 cells, co-culture with CSE-treated HBE cells or with exosomes derived from CSE-treated HBE cells resulted in the myofibroblast differentiation phenotype. Exosomal miR-21 was responsible for myofibroblast differentiation through hypoxia-inducible factor 1α (HIF-1α) signaling by targeting the von Hippel-Lindau protein (pVHL); HIF-1α transcriptionally regulated the α-SMA gene. For mice, downregulation of miR-21 prevented CS-induced airway remodeling. The levels of exosomal miR-21 were high in sera of smokers and COPD patients and inversely correlated with FEV1/FVC.Conclusion: We demonstrate that CS triggers the modification of exosome components and identify miR-21 derived from bronchial epithelial cells as a mediator of myofibroblast differentiation through the pVHL/HIF-1α signaling pathway, which has potential value for diagnosis and treatment of COPD.

No abstract

SummaryBackgroundData on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real‐world setting are limited.AimTo investigate TDF for preventing vertical transmission of HBV in real‐world practice.MethodsHepatitis B e‐antigen (HBeAg)‐positive mothers with HBV‐DNA >6 log10 IU/mL to receive TDF between gestational weeks 24‐33 and delivery were prospectively enrolled and followed until post‐partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother‐to‐child transmission rates. Secondary outcomes were maternal HBV‐DNA level suppression (<200 000 IU/mL) at delivery and HBeAg and hepatitis B surface antigen (HBsAg) serologic changes during the study.ResultsAmong 147 mothers enrolled, 143 started TDF and 143/144 infants completed the study. At delivery, 93.7% (134/143) of the mothers achieved HBV‐DNA<200 000 IU/L. On‐treatment, alanine aminotransferase (ALT) flares were observed in 8.4% (12/143) of mothers. After TDF cessation, ALT increased in 7.7% (11/143) of the mothers and 2.8% (4/143) achieved HBeAg negativity, but none had HBsAg loss. At birth, HBsAg was detected in 13.9% (20/144) of newborns and none at post‐partum week 28. Vertical transmission rates among infants were 0.7% (1/144, intention‐to‐treat) and 0% (per‐protocol). No infants had birth defects. No serious adverse effects were reported in either mothers or infants. Breastfeeding did not increase the HBV infection rate among infants although mothers had viral rebound after TDF cessation.ConclusionsTDF for highly viraemic mothers was well tolerated and reduced vertical transmission of HBV in a real‐world setting. There were no safety concerns during the postpartum 28‐week follow‐up.Registry number: Chinese Clinical Trial Registration No. ChiCTR‐OIC‐17010869

No abstract

Chinese university students often suffer from acute stress, which can affect their mental health. We measured and evaluated perceived stress in this population using the Simplified Chinese version of the 10-item Perceived Stress Scale (SCPSS-10). The SCPSS-10, Patient Health Questionnaire (PHQ), and Generalized Anxiety Disorder 7-item scale (GAD-7) were conducted in 1096 university students. Two weeks later, 129 participants were re-tested using the SCPSS-10. Exploratory factor analysis yielded two factors with Eigen values of 4.76 and 1.48, accounting for 62.41% of the variance. Confirmatory factor analysis demonstrated good fit of this two-factor model. The internal consistency reliability, as measured by Cronbach’s α, was 0.85. The test-retest reliability coefficient was 0.7. The SCPSS-10 exhibited high correlation with the PHQ-9 and GAD-7, indicating an acceptable concurrent validity. The SCPSS-10 exhibited satisfactory psychometric properties in Chinese university students.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. However, current biomarkers that discriminate HCC from liver cirrhosis (LC) are important but are limited. More reliable biomarkers for HCC diagnosis are therefore needed. Serum from HCC patients, LC patients and healthy volunteers were analyzed using NMR and LC/MS-based approach in conjunction with random forest (RF) analysis to discriminate their serum metabolic profiles. Thirty-two potential biomarkers have been identified, and the feasibility of using these biomarkers for the diagnosis of HCC was evaluated, where 100% sensitivity was achieved in detecting HCC patients even with AFP values lower than 20 ng/mL. The metabolic alterations induced by HCC showed perturbations in synthesis of ketone bodies, citrate cycle, phospholipid metabolism, sphingolipid metabolism, fatty acid oxidation, amino acid catabolism and bile acid metabolism in HCC patients. Our results suggested that these potential biomarkers identified appeared to have diagnostic and/or prognostic values for HCC, which deserve to be further investigated. In addition, it also suggested that RF is a classification algorithm well suited for selection of biologically relevant features in metabolomics.Hepatocellular carcinoma (HCC) is the most common intraabdominal malignancies and the third leading cause of cancer-related death worldwide, with a <7% 5-year survival rate.