Circ_0027791 contributes to the growth and immune evasion of hepatocellular carcinoma via the miR-496/programmed cell death ligand 1 axis in an m6A-dependent manner.

Emerging evidence indicates the critical roles of circular RNAs in the development of multiple cancers, containing hepatocellular carcinoma (HCC). Herein, our present research reported the biological function and mechanism of circ_0027791 in HCC progression. Circ_0027791, microRNA-496 (miR-496), programmed cell death ligand 1 (PDL1), and methyltransferase-like 3 (METTL3) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, invasion, and sphere formation ability were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, transwell, and sphere formation assays. Macrophage polarization was detected using flow cytometry assay. To understand the role of circ_0027791 during the immune escape, HCC cells were cocultured with peripheral blood mononuclear cells or cytokine-induced killer (CIK) cells in vitro. A xenograft mouse model was applied to assess the function of circ_0027791 in vivo. After prediction using circinteractome and miRDB, the binding between miR-496 and circ_0027791 or PDL1 was validated based on a dual-luciferase reporter assay. Interaction between METTL3 and circ_0027791 was determined using methylated RNA immunoprecipitation (MeRIP)-qPCR, RIP-qPCR, and RNA pull-down assays. Circ_0027791, PDL1, and METTL3 expression were upregulated, and miR-496 was decreased in HCC patients and cells. Moreover, circ_0027791 knockdown might repress proliferation, invasion, sphere formation, M2 macrophage polarization, and antitumor immune response. Circ_0027791 knockdown repressed HCC tumor growth in vivo. In mechanism, circ_0027791 functioned as a sponge for miR-496 to increase PDL1 expression. In addition, METTL3 mediated the m6A methylation of circ_0027791 and stabilized its expression. METTL3-induced circ_0027791 facilitated HCC cell progression partly regulating the miR-496/PDL1 axis, which provided a new prognostic and therapeutic marker for HCC.

Maternal parenting stress and social-emotional problems of Chinese preschoolers: The role of the mother-child relationship and maternal adverse childhood experiences.

BACKGROUND: Previous research suggests that maternal parenting stress is a significant predictor of social-emotional problems in children. However, little is known regarding the mother-child relationship and the effect of maternal adverse childhood experiences (ACEs) on this association. METHODS: Three waves of longitudinal panel data were collected from 2893 Chinese preschoolers with a follow-up interval of 6 months. The mothers of preschoolers were asked to complete anonymous questionnaires concerning demographic variables, maternal ACEs and parenting stress in Wave 1, mother-child relationships in Wave 2, and children's social-emotional problems in Wave 3. The parallel mediation model was conducted to analyze the mediating role of three dimensions of mother-child relationships, and the moderation model was conducted to examine the moderating role of maternal ACEs. RESULTS: The results showed that maternal parenting stress predicted children's social-emotional problems directly or indirectly through the mother-child relationship, with an intimate mother-child relationship mediating this main effect negatively but a conflicted and dependent mother-child relationship mediating this main effect positively. In addition, moderating results indicated that the main effect of maternal parenting stress on children's social-emotional problems was more marked among participants with at least one maternal ACEs than those without maternal ACEs. Furthermore, the moderating effect was only detected in children whose mothers had a high school education or less. LIMITATIONS: The subjectivity of mothers' reports may somewhat reduce the credibility due to the possible overestimation or underestimation of children's social-emotional problems. CONCLUSION: These findings provide new evidence for the effects of maternal parenting stress on children's social-emotional development and highlight the need for more attention to children with mothers having ACE exposure, lower educational level and poor parent-child relationships.

Mediating effects of parent-child relationship on the association between childhood maltreatment and depressive symptoms among adolescents.

BACKGROUND: Depressive symptoms are the most common mental disorder among adolescents, and its prevalence has been increasing in recent years. Although childhood maltreatment is a contributing factor to depressive symptoms among adolescents, the underlying mechanism of how this factor causes depressive symptoms is unclear. OBJECTIVE: This study aimed to investigate the mediating effects of parent-child relationship on the association between childhood maltreatment and depressive symptoms among adolescents and to identify how sex and only child status affect this association. METHODS: A total of 14,500 middle school students were randomly selected from four cities (Shenzhen, Zhengzhou, Nanchang, and Guiyang) in China. A survey questionnaire was administered to collect information on childhood maltreatment, parent-child relationship, and depressive symptoms. Pearson's correlation analysis was used in analyzing the relationship, Bootstrap method was used to test the mediating effects. A moderated mediation analysis has been used to determine the moderated mediation effect. RESULTS: Childhood maltreatment significantly negatively correlated with parent-child relationship and positively correlated with depressive symptoms (P < 0.001). The indirect effect of parent-child relationship accounted for 20.60% of the total effect between childhood maltreatment and depressive symptoms in all respondents and differed by sex (boys, 17.00%; girls, 25.23%) and only child status (only child, 15.61%; child with siblings, 23.49%). Besides, the indirect effect of the mediation model was moderated by sex and only child status. CONCLUSIONS: Childhood maltreatment increased the risk of depressive symptoms, and this relationship was partially mediated by parent-child relationship, sex and only child status have moderated the indirect relationship. These findings showed efforts aimed at enhancing the parent-child relationship may prevent or reduce the prevalence of depressive symptoms among adolescents, especially in girls and children with siblings.

Nesfatin-1 is a potential diagnostic biomarker for gastric cancer.

The lack of reliable plasma biomarkers limits their use in the diagnosis of gastric cancer (GC). The current study aimed to determine whether plasma nesfatin-1 can be used as a novel non-invasive biomarker for the diagnosis of GC. The levels of nesfatin-1 in 40 patients with GC and 40 healthy individuals, who were selected from the Chaohu Hospital Affiliated to Anhui Medical University, were assessed. ELISA was used for the measurement of plasma nesfatin-1 levels, while immunohistochemistry was applied to determine Ki67 protein expression in GC and normal gastric tissues. The diagnostic value of plasma nesfatin-1 for GC was further assessed using receiver operating characteristic (ROC) curve analysis. The results revealed that, compared with the controls, the mean nesfatin-1 levels in patients with GC were significantly increased. Furthermore, the protein expression of Ki67 in GC tissue was significantly upregulated compared with that in normal gastric tissue. Plasma nesfatin-1 levels were also demonstrated to be correlated with Ki67 protein expression in GC tissues. Additionally, ROC curve analysis indicated the potential diagnostic value of nesfatin-1, and the area under the ROC curve (AUC) for nesfatin-1 was 0.857 (95% confidence interval, 0.769-0.946). At a threshold nesfatin-1 level of 1.075 ng/ml, the optimal sensitivity and specificity were 70.0 and 95.0%, respectively, in discriminating patients with GC from healthy controls. These results indicated that plasma nesfatin-1 may serve as a novel biomarker for the diagnosis of GC and determination of GC cell proliferation.

Low KISS1 expression predicts poor prognosis for patients with colorectal cancer: A meta-analysis.

KISS1 and KISS1R, a novel pair of metastasis suppressors, are likely to be associated with the prognosis of colorectal cancer (CRC). Here, a meta-analysis was performed to study the role of KISS1 and KISS1R in CRC. Heterogeneity, stability and publication bias were all estimated. Six publications describing a total of 559 CRC patients were included in the present study. Low KISS1 expression predicted 70% higher risk of poor prognosis for general patients (HR, 1.71; 95% CI, 1.28-2.29) and 99% higher risk for East Asian patients (HR, 1.99; 95% CI, 1.46-2.72). Limited evidence indicated that decreased KISS1R expression might predict poor outcome (HR, 2.96; 95% CI, 1.51-5.82). Neither heterogeneity nor publication bias was identified. The current analyses suggest that low KISS1 expression predicts poor overall survival among East Asian patients with CRC. Evidence on other races and KISS1R are still insufficient, and additional studies are required to clarify the risk of CRC associated with KISS1R by race.

[Experimental study on effect of total flavone of Ginkgo biloba on delaying cell senescence].

OBJECTIVE: To investigate the mechanism of delaying the senescence of human diploid fibroblast (2BS) by total flavone of Ginkgo biloba (FG). METHODS: The drug sera of FG was used to treat the 2BS. The population doublings of 2BS cells were observed, the mRNA expression of P16 gene was determined by fluorescence real-time quantitative PCR. RESULTS: FG significantly extended the population doublings of 2BS cells, and decreased the expression of P16 mRNA. CONCLUSION: FG can delay the senescence of cells by inhibiting the P16 gene expression.