Circular RNA circ_RANBP9 exacerbates polycystic ovary syndrome via microRNA-136-5p/XIAP axis.

Polycystic ovary syndrome (PCOS) is an endocrine disease that affects the health of many women. Circular RNAs (circRNAs) are associated with the occurrence and progression of PCOS. This study aimed to explore the function of circ_RANBP9 in PCOS. First, the circ_RANBP9 level was found to be increased in the plasma of patients with PCOS and ovarian granulosa cells (GCs) using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR). In GCs, loss of circ_RANBP9 decelerated proliferation and accelerated apoptosis of KGN and COV434 cells, as determined by MTT assay, colony formation assay, and flow cytometry. Furthermore, bioinformatics analysis showed that circ_RANBP9 and XIAP can be targeted by the microRNA, miR-136-5p. Luciferase reporter assay and RNA pull-down assay further verified the interaction between miR-136-5p and circ_RANBP9 or XIAP. Importantly, knockdown of circ_RANBP9 suppressed proliferation and promoted apoptosis of KGN and COV434 cells, whereas inhibition of miR-136-5p reversed these effects. Additionally, XIAP abolished the repression of proliferation and acceleration of apoptosis induced by miR-136-5p. The promotion of apoptosis was accompanied by upregulation of caspase-3 and Bax, and downregulation of Bcl-2, as estimated by western blotting. In conclusion, silencing of circ_RANBP9 inhibited GC proliferation and facilitated apoptosis by mediating the miR-136-5p/XIAP pathway. These findings provide a new theoretical basis for screening and treatment of PCOS.

Genetic association between the HIF-1α P582S polymorphism and cervical cancer risk: a meta analysis.

BACKGROUND: Hypoxia-inducible factor-1 alpha (HIF-1α) P582S polymorphism has been reported to increase transactivation capacity of HIF-1α, which is prone to tumorigenesis. Several published case-control studies on the association between P582S polymorphism and cervical cancer have shown mixed results. In this study, we chose to perform a meta-analysis to assess the association. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis consisting of four studies with a total of 846 cases and 991 controls. All data were collected and overall comparison was performed among all subjects. Using the fixed effects model, the homozygous and the recessive models showed a significant increase in the risk of cervical cancer (the pooled OR=6.32, 95% CI=2.28-17.55, Phet=0.348; the pooled OR=5.86, 95% CI=2.13-16.11, Phet=0.394 respectively). Publication bias was not significantly indicated in this analysis. CONCLUSIONS: This meta-analysis demonstrates that HIF-1α P582S polymorphism may be associated with the risk of cervical cancer.

Association between CD95L polymorphism and cervical cancer risk: evidence from a meta-analysis.

Several studies have assessed the association of CD95L polymorphism with cervical cancer risk, but the data lack the power to provide compelling evidence. In this study, we aimed to clarify the association through a meta-analysis. A comprehensive search was conducted in PubMed, Embase, and Web of Science. The fixed-effects model was used to calculate odds ratio (OR) with 95 % confidence intervals (CIs). A total of five papers with six case-control studies were derived and finally included in this meta-analysis. The overall estimate did not reveal any significant association between CD95L -844C/T polymorphism and cervical cancer risk. Subgroup analysis in Asian population indicated nonsignificant nevertheless potentially increased risk in CC genotype carriers in comparison with the carriers of CT+TT genotypes (ORCC vs. CT+TT=1.16, 95 % CI=0.99-1.36, P for heterogeneity=0.231). Based on current epidemiological studies, this meta-analysis suggests that CD95L polymorphism may not be a risk factor contributing to cervical cancer development.

[Clinical study of maternal serum leptin levels as a predictor of gestational diabetes mellitus and gestational impaired glucose tolerance].

OBJECTIVE: To investigate whether maternal serum leptin level can be used as a predictor of gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). METHODS: Five hundred and eighty-three pregnant women were screened for GDM by the 50g oral glucose challenge test. At the same time, serum leptin levels were determined by radioimmunoassay, then the relationship between maternal serum leptin level and the incidence of GIGT and GDM was analyzed. According to the screening result, all the pregnant women were divided into three groups, the normal glucose group (NGT group), the gestational impaired glucose tolerance group (GIGT group), and gestational diabetes mellitus group (GDM group). GIGT group and GDM group were named as glucose intolerant group as a whole. RESULTS: (1) The serum leptin concentration of normal pregnant women ascended gradually from (7.0 +/- 1.8) microg/L in 24 gestational week to (9.4 +/- 2.1) microg/L during 34 - 36 gestational week, and then declined slightly but still maintained high level till delivery. (2) The serum leptin concentration of the glucose intolerant pregnant women ranged from (11.3 +/- 3.1) microg/L to(14.5 +/- 4.3) microg/L, and showed no difference among different gestational weeks (P > 0.05). (3) Serum leptin level of glucose intolerant women was (12.5 +/- 3.5) microg/L on average, much higher than that of NGT group, (8.5 +/- 2.6) microg/L (P < 0.05), and this difference remained in any gestational week (P < 0.05). (4) Most of the GDM clustered in the higher leptin level groups and 66.7% GDM had a serum leptin level higher than 14.0 microg/L. Moreover, 64.7% of women whose serum leptin level was above 17.0 microg/L had different degree of glucose intolerance. Serum leptin level positively correlated with the incidence of GIGT and GDM. CONCLUSION: Serum leptin level is correlated with glucose tolerance during pregnancy. Its abnormal increase during pregnancy might have a predictive value for GDM and GIGT.

Contribution of I(K,ADO) to the negative dromotropic effect of adenosine.

OBJECTIVE: Despite the pathophysiological and therapeutic significance of the negative dromotropic effect of adenosine, its underlying ionic mechanism, and specifically the role of the adenosine-activated K(+) current (I(K,ADO)) is not experimentally defined. Therefore, we studied the contribution of I(K,ADO) to the negative dromotropic effect of adenosine. METHODS: Effects of adenosine on single atrioventricular nodal and left atrial myocytes from rabbits were studied using the whole cell configuration of the patch clamp technique. Complementary experiments were done in rabbit and guinea pig isolated hearts instrumented to measure the atrium-to-His bundle interval. RESULTS: In contrast to its effect in atrial myocytes, Ba(2+) selectively and completely blocked I(K,ADO) at membrane potentials from -70 to 0 mV in atrioventricular nodal myocytes and abolished the adenosine-induced leftward shift of the reversal membrane potential. Ba(2+) alone did not significantly prolong the A-H interval, but markedly attenuated the A-H interval prolongation caused by adenosine. In guinea pig heart, EC(50) values ( pD(2) +/- SEM) for adenosine-induced atrium-to-His bundle interval prolongation were 3.3 micromol/L (5.48 +/- 0.04) and 13.2 micromol/L (4.88 +/- 0.05, P < 0.001) in the absence and presence of Ba(2+), respectively. Despite species-dependent differences in sensitivities to adenosine (guinea pig > rabbit), the relative contribution of adenosine-activated K(+) current to the atrium-to-His bundle interval prolongation was nearly identical. In guinea pig hearts it ranged from 37.8 % (P = 0.013) to 72.5 % (P < 0.001) at 2 to 6 micromol/L adenosine, respectively. CONCLUSION: I(K,ADO) contributes significantly to the negative dromotropic effect of adenosine, but predominantly at relatively high concentrations of the nucleoside.