Curcumin inhibits esophageal squamous cell carcinoma progression through down-regulating the circNRIP1/miR-532-3p/AKT pathway.

Curcumin shows an anti-cancer role in many kinds of tumors. However, the mechanism of its anti-tumor function in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Herein, we explored the therapeutic potential of curcumin for esophageal cancer. Curcumin could time- and dose-dependently inhibit ESCC cells activity. Additionally, ESCC cells exposed to 20 µM of curcumin exhibited significantly decreased proliferative and invasive capacities, as well as enhanced cell apoptosis. ESCC tissues and cells exhibited significantly increased circNRIP1 expression when compared to their counterparts. circNRIP1 knockdown markedly impaired cell proliferation, clone formation, cell migration and invasion but promoted apoptosis. Exposure to 10-20 µM of curcumin inhibited circNRIP1 expression, however, overexpression of circNRIP1 could significantly restored the biological characteristics that were inhibited by curcumin exposure in vivo and in vitro. circNRIP1 promoted the malignancy of ESCC by combining miR-532-3p, and downstream AKT3. Curcumin inhibited AKT phosphorylation by up-regulating miR-532-3p expression, thereby inhibiting the activation of the AKT pathway. In summary, curcumin is a potent inhibitor of ESCC growth, which can be achieved through the regulation of the circNRIP1/miR-532-3p/AKT pathway. This research may provide new mechanisms for curcumin to inhibit the malignant development of ESCC.

Comprehensive analysis of RNA m6A methylation in pressure overload-induced cardiac hypertrophy.

AIM: To analyze and compare the mRNA N6-methyladenosine modifications in transverse aortic constriction induced mice hearts and normal mice hearts. MATERIALS AND METHODS: Colorimetric quantification was used to probe the changes in m6A modifications in the total RNA. The expression of m6A-related enzymes was analyzed via qRT-PCR and western blotting. RNA-seq and MeRIP-seq were performed to identify genes with differences in m6A modifications or expression in the transcriptome profile. RESULTS: Compared with the control group, the TAC group exhibited higher m6A methylation levels. FTO and WTAP were downregulated after TAC, while METTL3 was significantly downregulated at the protein level. MeRIP-seq revealed that 1179 m6A peaks were upmethylated and 733 m6A peaks were downmethylated, and biological analysis of these genes exhibited a strong relationship with heart function. CONCLUSION: Our findings provide novel information regarding m6A modification and gene expression changes in cardiac hypertrophy, which may be fundamental for further research.

Junctophilin-2 allosterically interacts with ryanodine receptor type 2 to regulate calcium release units in mouse cardiomyocytes.

The interaction between junctophilin-2 (JPH2) and ryanodine receptor type 2 (RyR2) regulated Ca2+ signaling in mouse cardiomyocytes. However, their exact interaction remains unclear. This study elucidates the interaction between JPH2 with RyR2 using co-immunoprecipitation of cardiac sarcoplasmic reticulum vesicles. Additionally, a glutathione S-transferase (GST) pull-down analysis was performed to investigate the physical interaction between RyR2 and JPH2 fragments. JPH2 interacted with RyR2 and the C terminus of the JPH2 protein can pull-down RyR2 receptors. Confocal immunofluorescence imaging indicated that the majority of JPH2 and RyR2 proteins were colocalized near Z-lines in isolated mouse cardiomyocytes. Knockdown of JPH2 reduced the amplitude of Ca2+ transients and disrupted its interaction with RyR2. Therefore, the C-terminus domain of JPH2 is required for interactions with RyR2 in mouse cardiomyocytes, which provides a molecular mechanism for seeking Ca2+-related disease prevention strategies.

The MORN domain of Junctophilin2 regulates functional interactions with small-conductance Ca2+ -activated potassium channel subtype2 (SK2).

Small-conductance Ca2+ -activated K+ channel subtype2 (SK2) are stable macromolecular complexes that regulate myocardial excitability and Ca2+ homeostasis. Junctophilin-2 (JP2) is a membrane-binding protein, which provides functional crosstalk by physically linking with the cell-surface and intracellular ion channels. We previously demonstrated that the MORN domain of JP2 interacts with SK2 channels. However, the roles of the JP2 MORN domain in regulating the precise subcellular localization and molecular modulation of SK2 have not yet been incompletely understood. In the present study, in vitro and in vivo assays were used to confirm the physical interactions between the SK2 channel and JP2 in H9c2 and HEK293 cells, with a concentration on the association between the C-terminus of SK2 channels and the MORN domain of JP2. Furthermore, the membrane expression of SK2 were found to be significantly impaired by the mutation or knockdown of JP2. Using immunofluorescence staining along with Golgi/early endosome markers, we studied the mechanisms of JP2-regulated SK2 membrane trafficking, which indicates that the JP2 MORN domain is probably necessary for the retrograde trafficking of SK2 channels. The functional study demonstrates that whole cell SK2 current densities recorded from the HEK293 cells co-expressing the JP2-MORN domain with SK2 were significantly augmented, compared with cells expressing SK2 alone. Our findings suggest that the MORN domain of JP2 directly modulates SK2 channel current amplitude and trafficking, through its interaction with an overlapping region of the JP2 MORN domain on the SK2 C-terminus.

Abdominal circumference profiles of macrosomic infants born to mothers with or without hyperglycemia in China.

Objectives: Serial measurements of sonographic fetal abdominal circumference (AC) are useful for monitoring fetal growth during pregnancy and are essential for predicting macrosomia. The study was aiming to compare the AC profiles of infants born to mothers with or without hyperglycemia in Chinese population.Subjects and methods: The "GDM Prevalence Study (GPS)" was a large study conducted in 22 hospitals in three large cities in China, which included 34,085 NGT (normal glucose tolerant) women, 8272 GDM (gestational diabetes mellitus) women and 729 DM (diabetes mellitus) women. A total of 116,740 scans and 103,377 valid AC measurements were performed for the NGT, GDM and DM groups at different gestational age. AC profiles and fetal growth rates at different stages of pregnancy were compared between different groups.Results: The overall AC growth rate (ß) was higher in the macrosomia group than in the no macrosomia group in NGT (ß =10.250 versus 9.541, p < .001), GDM (ß = 10.572 versus 9.705, p < .001) and DM (ß = 11.363 versus 9.924, p < .001) pregnancies. Significant differences were observed between NGT-macrosomia, GDM-macrosomia and DM-macrosomia. Significant differences were also noted between NGT-no macrosomia, GDM-no macrosomia and DM-no macrosomia women. Participants in NGT-macrosomia group exhibited larger AC values than NGT-no macrosomia group beginning at 21 gestational weeks, and GDM-macrosomia group exhibited larger AC values than GDM-no macrosomia group beginning at 22 gestational weeks. AC growth rate was higher in NGT-macrosomia and GDM-macrosomia groups than in the corresponding no macrosomia groups between 22 and 30 gestational weeks.Conclusions: The overall AC growth rates are higher in macrosomia group compared to the no macrosomia group in NGT, GDM as well as DM participants. The significant difference of AC growth rates in NGT-macrosomia and GDM-macrosomia indicate the possible differential underlying mechanisms in developing macrosomia with or without hyperglycemia exposure. Our study demonstrate that larger fetal AC measurements around 21-22 weeks are associated with subsequent diagnosis of macrosomia, suggesting that macrosomia management should be initiated much earlier than we thought.

Complete Genome Sequence of Senecavirus A Strain SVV HN16 Identified in China.

A virus that caused blisters and ulcers in pigs in China was detected to be a strain of Senecavirus A (SVA). Complete genome sequencing and analysis results showed that the isolate shares 93.8% to 99.1% identity with other isolates that have been reported, proving that a new isolate of SVA was found in China.

Analysis of correlation factors and pregnancy outcomes of hypertensive disorders of pregnancy - a secondary analysis of a random sampling in Beijing, China.

OBJECTIVE: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China. STUDY DESIGN: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA). RESULTS: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group. CONCLUSIONS: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.

Is It Time to Change Our Reference Curve for Femur Length? Using the Z-Score to Select the Best Chart in a Chinese Population.

OBJECTIVE: To use Z-scores to compare different charts of femur length (FL) applied to our population with the aim of identifying the most appropriate chart. METHODS: A retrospective study was conducted in Beijing. Fifteen hospitals in Beijing were chosen as clusters using a systemic cluster sampling method, in which 15,194 pregnant women delivered from June 20th to November 30th, 2013. The measurements of FL in the second and third trimester were recorded, as well as the last measurement obtained before delivery. Based on the inclusion and exclusion criteria, we identified FL measurements from 19996 ultrasounds from 7194 patients between 11 and 42 weeks gestation. The FL data were then transformed into Z-scores that were calculated using three series of reference equations obtained from three reports: Leung TN, Pang MW et al (2008); Chitty LS, Altman DG et al (1994); and Papageorghiou AT et al (2014). Each Z-score distribution was presented as the mean and standard deviation (SD). Skewness and kurtosis and were compared with the standard normal distribution using the Kolmogorov-Smirnov test. The histogram of their distributions was superimposed on the non-skewed standard normal curve (mean = 0, SD = 1) to provide a direct visual impression. Finally, the sensitivity and specificity of each reference chart for identifying fetuses <5th or >95th percentile (based on the observed distribution of Z-scores) were calculated. The Youden index was also listed. A scatter diagram with the 5th, 50th, and 95th percentile curves calculated from and superimposed on each reference chart was presented to provide a visual impression. RESULTS: The three Z-score distribution curves appeared to be normal, but none of them matched the expected standard normal distribution. In our study, the Papageorghiou reference curve provided the best results, with a sensitivity of 100% for identifying fetuses with measurements < 5th and > 95th percentile, and specificities of 99.9% and 81.5%, respectively. CONCLUSIONS: It is important to choose an appropriate reference curve when defining what is normal. The Papageorghiou reference curve for FL seems to be the best fit for our population. Perhaps it is time to change our reference curve for femur length.

Risk of adverse pregnancy outcomes stratified for pre-pregnancy body mass index.

OBJECTIVE: To estimate the risk of adverse maternal and perinatal outcomes in women with different pre-pregnancy body mass index (BMI). METHODS: We conducted a cohort study with 14 451 singleton pregnancies in 15 medical centers in Beijing between 20 June 2013 and 30 November 2013 using cluster random sampling. We divided participants into four groups based on pre-pregnancy BMI: Group A (underweight): BMI < 18.5 kg/m(2), Group B (normal): 18.5-23.9 kg/m(2), Group C (overweight): 24-27.9 kg/m(2), Group D (obesity): ≥28 kg/m(2). We used multivariate analysis to evaluate the association of the risk of adverse pregnancy outcomes and pre-pregnancy BMI. RESULTS: The prevalence of maternal overweight and obesity was 14.82% (2142/14 451) and 4.71% (680/14 451) in the study population, respectively. Higher pre-pregnancy BMI is associated with higher prevalence of gestational diabetes (GDM), macrosomia, Cesarean section (C-section), preeclampsia and postpartum hemorrhage. Pre-pregnancy overweight or obesity increases the risk of adverse pregnancy outcomes, regardless of GDM status. CONCLUSIONS: Pre-pregnancy overweight or obesity is associated with increased risk of adverse pregnancy outcomes. Nutrition counseling is recommended before pregnancy in women who have overweight or obesity.