scholarly journals circCRAMP1L is a novel biomarker of preeclampsia risk and may play a role in preeclampsia pathogenesis via regulation of the MSP/RON axis in trophoblasts

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yonggang Zhang ◽  
Hongling Yang ◽  
Yipeng Zhang ◽  
Junzhu Shi ◽  
Ronggui Chen

Abstract Background Preeclampsia is a severe disease in pregnant women, which is primarily managed by early screening and prevention. Circular RNAs (circRNAs) have increasingly been shown to be important biological regulators involved in numerous diseases. Further, increasing evidence has demonstrated that circRNAs can be used as diagnostic biomarkers. This study was conducted to evaluate the potential of circCRAMP1L, previously identified to be downregulated in preeclampsia, as a novel biomarker for predicting the development of preeclampsia. Methods We measured the expression of circCRAMP1L, which is reportedly relevant to trophoblast physiology, in plasma samples from 64 patients with preeclampsia and 64 age-, gestational age-, and body mass index-matched healthy pregnant women by qRT-PCR. MTT proliferation and transwell invasion assays revealed the biological role of circCRAMP1L in preeclampsia pathogenesis. RNA immunoprecipitation and dual-luciferase reporter assays clarified the mechanism underlying the biological function of circCRAMP1L in TEV-1 cells. Results circCRAMP1L circulating levels were significantly lower in patients with preeclampsia (2.66 ± 0.82, △Ct value) than in healthy pregnant women (3.95 ± 0.67, △Ct value, p <  0.001). The area under the receiver operating characteristic curve for circCRAMP1L was 0.813. Univariate and multivariate analyses identified circCRAMP1L as an independent predictor of preeclampsia. Furthermore, when circCRAMP1L was utilised in combination with its target protein macrophage stimulating protein (MSP), the predictive performance increased, with an area under the receiver operating characteristic curve of 0.928 (95% CI 0.882–0.974), 80.0% sensitivity, and 80.0% specificity. The in vitro results indicated that circCRAMP1L regulates cell proliferation, and invasion via MSP and RON proteins. We investigated the molecular mechanisms of these effects. In vitro, relative to the control group, circCRAMP1L overexpression significantly enhanced cell proliferation; furthermore, trophoblast cell invasion increased proportionally with circCRAMP1L expression. RNA immunoprecipitation and luciferase reporter gene illustrated that circCRAMP1L participated in regulation of trophoblast cell by regulating MSP. Conclusion Reduced plasma levels of circCRAMP1L may be associated with an increased risk of preeclampsia, and circCRAMP1L may be a novel biomarker of preeclampsia risk.

2020 ◽  
Vol 9 (14) ◽  
Author(s):  
Ran Chu ◽  
Wei Chen ◽  
Guangmin Song ◽  
Shu Yao ◽  
Lin Xie ◽  
...  

Background Women with congenital heart disease are considered at high risk for adverse events. Therefore, we aim to establish 2 prediction models for mothers and their offspring, which can predict the risk of adverse events occurred in pregnant women with congenital heart disease. Methods and Results A total of 318 pregnant women with congenital heart disease were included; 213 women were divided into the development cohort, and 105 women were divided into the validation cohort. Least absolute shrinkage and selection operator was used for predictor selection. After validation, multivariate logistic regression analysis was used to develop the model. Machine learning algorithms (support vector machine, random forest, AdaBoost, decision tree, k‐nearest neighbor, naïve Bayes, and multilayer perceptron) were used to further verify the predictive ability of the model. Forty‐one (12.9%) women experienced adverse maternal events, and 93 (29.2%) neonates experienced adverse neonatal events. Seven high‐risk factors were discovered in the maternal model, including New York Heart Association class, Eisenmenger syndrome, pulmonary hypertension, left ventricular ejection fraction, sinus tachycardia, arterial blood oxygen saturation, and pregnancy duration. The machine learning–based algorithms showed that the maternal model had an accuracy of 0.76 to 0.86 (area under the receiver operating characteristic curve=0.74–0.87) in the development cohort, and 0.72 to 0.86 (area under the receiver operating characteristic curve=0.68–0.80) in the validation cohort. Three high‐risk factors were discovered in the neonatal model, including Eisenmenger syndrome, preeclampsia, and arterial blood oxygen saturation. The machine learning–based algorithms showed that the neonatal model had an accuracy of 0.75 to 0.80 (area under the receiver operating characteristic curve=0.71–0.77) in the development cohort, and 0.72 to 0.79 (area under the receiver operating characteristic curve=0.69–0.76) in the validation cohort. Conclusions Two prenatal risk assessment models for both adverse maternal and neonatal events were established, which might assist clinicians in tailoring precise management and therapy in pregnant women with congenital heart disease.


2016 ◽  
Vol 101 (3) ◽  
pp. 1290-1298 ◽  
Author(s):  
Chenyan Li ◽  
Shiqiao Peng ◽  
Xiaomei Zhang ◽  
Xiaochen Xie ◽  
Danyang Wang ◽  
...  

Abstract Context: Iodine nutrition is a global event, especially for pregnant women. Objective: To develop applicable index of iodine intake for population during pregnancy. Design, Setting, and Participants: From 2012 to 2014, pregnant women at less than 8 weeks of gestation (n = 222) and reproductive-age women (n = 827) participated in this study. The pregnant women were evaluated at follow-up visits at 8, 12, 16, 20, 28, and 36 weeks of gestation and 3 and 6 months postpartum. Main Outcome Measures: Twenty-four-hour urine samples were collected at weeks 8 of gestation. Urine iodine (UI) and creatinine (Cr) and serum thyroglobulin were measured in all of the subjects. Circulatory iodine was measured using inductively coupled plasma-mass spectrometry at 8, 20, and 36 weeks of gestation and 6 months postpartum. Results: The median UI concentration decreased from 183.6 to 104.2 μg/L during pregnancy. The serum iodine (SI) changes were similar to the UI to creatinine ratio (UI/Cr). The SI level was lowest at the eighth week of gestation (60.5 μg/L), which rose significantly until 20 weeks (106.5 μg/L) and then began to decline (36 wk, 84.7 μg/L). The 24-hour UI excretion measurement was regarded as the gold standard. The area under the receiver-operating characteristic curve for UI/Cr was 0.92 for iodine deficiency diagnoses and 0.78 for SI. The area for SI was 0.82 for excessive iodine diagnoses and 0.75 for UI/Cr. The areas under these curves were significantly different (P &lt; .001). The areas under the receiver-operating characteristic curve for UI were 0.61 (P = .11) and 0.65 (P = .08) for iodine deficiency and excessive iodine diagnoses, respectively. Additionally, for thyroglobulin, these values were 0.54 (P = .53) and 0.53 (P = .74), respectively. Conclusions: Iodine intake, as assessed by spot UI concentration in pregnant women, is inaccurate and increases the prevalence of iodine deficiency. The UI/Cr better reflects the 24-hour iodine excretion and circulating iodine levels during pregnancy and the postpartum period.


2020 ◽  
Author(s):  
Zhisen Shen ◽  
Jun Li ◽  
Dong Ye ◽  
Hongxia Deng ◽  
Shanshan Gu ◽  
...  

Abstract Background: Transfer RNA (tRNA) is a ubiquitous RNA, present in all life forms and considered a housekeeping gene with limited regulatory function. Recent studies have shown that tRNA is dysregulated and involved in the pathogenic process of cancer.Methods: Quantitative reverse transcription-polymerase chain reaction detected the relative expression levels of tRNAIniCAT in paired LSCC tissues and paracancerous tissues and preoperative, postoperative, and healthy human plasma. We analyzed the relationship between its expression level and the clinicopathological features of patients. We also established the receiver operating characteristic curve and predicted its diagnostic value. High expression of tRNAIniCAT was detected in the LSCC cell line. The proliferation, apoptosis, and cycle of cells were analyzed. High expression of tRNAIniCAT was detected in mice with transplanted tumors. The tumor weight and volume in mice were measured. The transplanted tumor was used for pathological analysis and transmission electron microscope observation.Results: tRNAIniCAT was down-regulated in LSCC tissues and plasma. The area under the plasma receiver operating characteristic curve was 0.808. High expression of tRNAIniCAT in the laryngeal carcinoma cell line inhibited cell proliferation and promoted apoptosis. High expression of tRNAIniCAT in transplanted tumor in nude mice inhibited the growth of the transplanted tumor.Conclusion: tRNAIniCAT acts as a tumor Inhibitor in LSCC, inhibits cell proliferation, and promotes apoptosis in vitro and in vivo. tRNAIniCAT may be used as a new biomarker for the early diagnosis of LSCC.


2019 ◽  
Vol 30 (7-8) ◽  
pp. 221-228
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh ◽  
Nicholas Hobbs ◽  
Jigar Shah ◽  
Matthew Harris ◽  
...  

Aims To investigate whether an intraperitoneal contamination index (ICI) derived from combined preoperative levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin could predict the extent of intraperitoneal contamination in patients with acute abdominal pathology. Methods Patients aged over 18 who underwent emergency laparotomy for acute abdominal pathology between January 2014 and October 2018 were randomly divided into primary and validation cohorts. The proposed intraperitoneal contamination index was calculated for each patient in each cohort. Receiver operating characteristic curve analysis was performed to determine discrimination of the index and cut-off values of preoperative intraperitoneal contamination index that could predict the extent of intraperitoneal contamination. Results Overall, 468 patients were included in this study; 234 in the primary cohort and 234 in the validation cohort. The analyses identified intraperitoneal contamination index of 24.77 and 24.32 as cut-off values for purulent contamination in the primary cohort (area under the curve (AUC): 0.73, P < 0.0001; sensitivity: 84%, specificity: 60%) and validation cohort (AUC: 0.83, P < 0.0001; sensitivity: 91%, specificity: 69%), respectively. Receiver operating characteristic curve analysis also identified intraperitoneal contamination index of 33.70 and 33.41 as cut-off values for feculent contamination in the primary cohort (AUC: 0.78, P < 0.0001; sensitivity: 87%, specificity: 64%) and validation cohort (AUC: 0.79, P < 0.0001; sensitivity: 86%, specificity: 73%), respectively. Conclusions As a predictive measure which is derived purely from biomarkers, intraperitoneal contamination index may be accurate enough to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology and to facilitate decision-making together with clinical and radiological findings.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Mi ◽  
Pengfei Qu ◽  
Na Guo ◽  
Ruimiao Bai ◽  
Jiayi Gao ◽  
...  

Abstract Background For most women who have had a previous cesarean section, vaginal birth after cesarean section (VBAC) is a reasonable and safe choice, but which will increase the risk of adverse outcomes such as uterine rupture. In order to reduce the risk, we evaluated the factors that may affect VBAC and and established a model for predicting the success rate of trial of the labor after cesarean section (TOLAC). Methods All patients who gave birth at Northwest Women’s and Children’s Hospital from January 2016 to December 2018, had a history of cesarean section and voluntarily chose the TOLAC were recruited. Among them, 80% of the population was randomly assigned to the training set, while the remaining 20% were assigned to the external validation set. In the training set, univariate and multivariate logistic regression models were used to identify indicators related to successful TOLAC. A nomogram was constructed based on the results of multiple logistic regression analysis, and the selected variables included in the nomogram were used to predict the probability of successfully obtaining TOLAC. The area under the receiver operating characteristic curve was used to judge the predictive ability of the model. Results A total of 778 pregnant women were included in this study. Among them, 595 (76.48%) successfully underwent TOLAC, whereas 183 (23.52%) failed and switched to cesarean section. In multi-factor logistic regression, parity = 1, pre-pregnancy BMI < 24 kg/m2, cervical score ≥ 5, a history of previous vaginal delivery and neonatal birthweight < 3300 g were associated with the success of TOLAC. The area under the receiver operating characteristic curve in the prediction and validation models was 0.815 (95% CI: 0.762–0.854) and 0.730 (95% CI: 0.652–0.808), respectively, indicating that the nomogram prediction model had medium discriminative power. Conclusion The TOLAC was useful to reducing the cesarean section rate. Being primiparous, not overweight or obese, having a cervical score ≥ 5, a history of previous vaginal delivery or neonatal birthweight < 3300 g were protective indicators. In this study, the validated model had an approving predictive ability.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Kahles ◽  
R.W Mertens ◽  
M.V Rueckbeil ◽  
M.C Arrivas ◽  
J Moellmann ◽  
...  

Abstract Background GLP-1 and GLP-2 (glucagon-like peptide-1/2) are gut derived hormones that are co-secreted from intestinal L-cells in response to food intake. While GLP-1 is known to induce postprandial insulin secretion, GLP-2 enhances intestinal nutrient absorption and is clinically used for the treatment of patients with short bowel syndrome. The relevance of the GLP-2 system for cardiovascular disease is unknown. Purpose The aim of this study was to assess the predictive capacity of GLP-2 for cardiovascular prognosis in patients with myocardial infarction. Methods Total GLP-2 levels, NT-proBNP concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 918 patients with myocardial infarction, among them 597 patients with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (3-P-MACE) with a median follow-up of 311 days. Results Kaplan-Meier survival plots (separated by the median of GLP-2 with a cut-off value of 4.4 ng/mL) and univariable cox regression analyses found GLP-2 values to be associated with adverse outcome (logarithmized GLP-2 values HR: 2.87; 95% CI: 1.75–4.68; p&lt;0.0001). Further adjustment for age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, family history of cardiovascular disease, hs-Troponin T, NT-proBNP and hs-CRP levels did not affect the association of GLP-2 with poor prognosis (logarithmized GLP-2 values HR: 2.96; 95% CI: 1.38–6.34; p=0.0053). Receiver operating characteristic curve (ROC) analyses illustrated that GLP-2 is a strong indicator for cardiovascular events and proved to be comparable to other established risk markers (area under the curve of the combined endpoint at 6 months; GLP-2: 0.72; hs-Troponin: 0.56; NT-proBNP: 0.70; hs-CRP: 0.62). Adjustment of the GRACE risk estimate by GLP-2 increased the area under the receiver-operating characteristic curve for the combined triple endpoint after 6 months from 0.70 (GRACE) to 0.75 (GRACE + GLP-2) in NSTEMI patients. Addition of GLP-2 to a model containing GRACE and NT-proBNP led to a further improvement in model performance (increase in AUC from 0.72 for GRACE + NT-proBNP to 0.77 for GRACE + NT-proBNP + GLP-2). Conclusions In patients admitted with acute myocardial infarction, GLP-2 levels are associated with adverse cardiovascular prognosis. This demonstrates a strong yet not appreciated crosstalk between the heart and the gut with relevance for cardiovascular outcome. Future studies are needed to further explore this crosstalk with the possibility of new treatment avenues for cardiovascular disease. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Society of Cardiology (DGK), German Research Foundation (DFG)


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