Association of air temperature exposure during pregnancy with risk of preeclampsia in Guangzhou, China.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression.

Pre-eclampsia (PE) is a severe pregnancy disorder that poses a significant health risk to both mother and fetus, with no preventive or therapeutic measures. Our previous research suggested an association between elevated SERPINA5 levels and PE features. This study investigated whether SERPINA5 could be a potential therapeutic target for PE. We established PE-like features in pregnant rats using L-NAME (75 mg/kg/d) treatment. Adenoviruses carrying overexpressed or suppressed SERPINA5 genes were intravenously injected into these PE rats on the fifth and seventh days of pregnancy. We evaluated the rats' systolic blood pressure, urine protein concentration, and placental and fetal metrics and histology. Placental gene expression following SERPINA5 overexpression was evaluated using mRNA sequencing. The L-NAME-induced PE rat model observed a significant increase in placental and peripheral SERPINA5 levels. The overexpression of SERPINA5 exacerbated L-NAME-induced hypertension and proteinuria in pregnant rats. A histology examination revealed a smaller placental junctional zone in L-NAME + overexpressing rats. Placental gene expression analysis in the L-NAME + overexpressing group indicated increased coagulation activation. L-NAME-induced hypertension and proteinuria were mitigated when SERPINA5 expression was suppressed. Additionally, placental development was improved in the SERPINA5-suppressed group. Our findings suggested that SERPINA5 may worsen L-NAME-induced PE-like features by promoting the activation of the coagulation cascade. Therefore, reducing SERPINA5 expression could potentially serve as a therapeutic strategy for PE.

Limosilactobacillus reuteri ameliorates preeclampsia in mice via improving gut dysbiosis and endothelial dysfunction.

BACKGROUND: As a leading cause of maternal and neonatal morbidity and mortality, preeclampsia (PE) remains enigmatic. We confirmed that PE is associated with gut dysbiosis. However, whether probiotics could improve PE via regulating gut microbiota remains unclear. Exploring specific probiotic that could alleviate PE by modulating gut microbiota and elucidating detailed mechanisms will be essential for treating PE. METHODS: PE model was induced by nitric oxide (NO) inhibition with L-NAME in mice, and treated with Limosilactobacillus reuteri (L. reuteri). 16 S rDNA analysis was conducted on feces from mice. In vitro and in vivo experiments were performed to explore the roles and mechanisms of L. reuteri in PE. RESULTS: NO inhibition by L-NAME induced PE and gut dysbiosis in mice, characterized by differential gut microbiome, reduced alpha diversity, and markedly decreased abundance of Lactobacillales and L. reuteri. Importantly, L. reuteri could improve PE induced by L-NAME in mice, and ameliorate the gut dysbiosis of PE mice, including restorative gut microbiota composition, increased alpha diversity, and upregulated L. reuteri content. Moreover, L. reuteri could improve NO synthesis, angiogenesis, inflammation and oxidative stress of PE mice. Consistently, L. reuteri could ameliorate NO synthesis, endothelial dysfunction and inflammation mediated by L-NAME in vitro. CONCLUSIONS: Our results reveal that L. reuteri could ameliorate PE induced by NO inhibition in mice via improving gut dysbiosis and endothelial dysfunction, supporting gut microbiota serving as therapeutic target for treating PE originated from endothelial dysfunction and L. reuteri protecting patients from PE via modulating gut microbiota and endothelial function.

Fibrinogen beta chain may be a potential predict biomarker for pre-eclampsia: A preliminary study.

OBJECTIVE: There are no approaches for the early detection of pre-eclampsia (PE). Using parallel reaction monitoring proteomics, we investigated 79 maternal serum protein changes before PE onset and its predictive capability. METHODS: We conducted a nested case-control study with 60 PE patients and 60 normotensive pregnant women matched for age and gestational week. These differentially expressed proteins were quantified using the data-dependent acquisition (DDA) combined parallel response monitoring (PRM) approach, and a PE prediction model was developed using the least absolute shrinkage and selection operator (LASSO) regression. We further examined the link between these biomarkers and PE using bioinformatics. ELISA assay was used to investigate the expression and clinical significance of the critical variables. RESULTS: Among the 79 analyzed proteins, we identified 11 serum proteins with significantly abnormal expression. Fibrinogen beta chain (FGB) was likely connected with the progression of PE due to the positive correlation between their levels and those of hypertension and proteinuria. In addition, an early prediction model for PE with an AUC of 92% was developed using LASSO regression. CONCLUSION: Our research employs predictive algorithms and screens for relevant variables, which could result in a potential approach to enhancing PE prediction.

SERPINA5 may promote the development of preeclampsia by disruption of the uPA/uPAR pathway.

Preeclampsia (PE) is the leading cause of maternal and fetal morbidity or mortality but lacks reliable methods for early diagnosis. In a previous study, serum SERPINA5 levels were higher in women with PE before the clinical manifestation of the disease. This study aimed to evaluate the efficacy of SERPINA5 in predicting PE and investigate its role in trophoblast cell biology. A multicenter, 2-stage observational case-control study was performed to develop and validate an early predictive PE model based on SERPINA5, maternal characteristics, and inflammatory factors. To further understand the relationship between SERPINA5 and PE, SERPINA5 was overexpressed or knocked down in extravillous trophoblast cells (EVT) and a pregnant rat model. After development and initial validation, a model that combined SERPINA5 and inflammatory factors had a high predictive ability for PE before 20 weeks gestation with an AUC of 0.90 (95% CI 0.83-0.96). It also demonstrated that SERPINA5 inhibited primary EVT cell invasion by disrupting the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor (uPA/uPAR) pathway, in turn, is involved in the development of PE. In vivo experiments also proved that overexpression of SERPINA5 induced a PE-like syndrome (hypertension and proteinuria) in pregnant rats. Therefore, serum SERPINA5 is a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on the uPA/uPAR system prior to the clinical manifestation of PE.

The potential risk factors of placenta increta and the role of octamethylcyclotetrasiloxane.

BACKGROUND: The study aimed to investigate the potential risk factors for the placenta accreta spectrum (PAS), determine the predictive value of a diagnostic model, and evaluate the effects of octamethylcyclotetrasiloxane (OMCTS) on trophoblast proliferation and migration. METHODS: This case-control study included 244 pregnant women with PAS and 327 normal pregnant women who visited Guangzhou Women and Children's Medical Centre, China, from January 2014 to December 2017. Blood was collected from 42 women with PAS and 77 controls, and plasma specimens were analyzed by gas chromatography-time-of-flight mass spectrometry. In addition, the proliferation and migration of trophoblast cells were examined after treatment with OMCTS. RESULTS: We found an association between the risk of PAS and clinical factors related to fasting blood glucose levels (BS0, OR = 5.78), as well as factors related to endometrial injury [history of cesarean section (OR = 179.59), uterine scarring (OR = 68.37), and history of abortion (OR = 5.66)]. Equally important, pregnant women with PAS had significantly higher plasma OMCTS concentrations than controls. In vitro, we found that OMCTS could promote the proliferation and migration of HTR8/SVneo cells. The model of combining clinical factors and OMCTS had a good performance in PAS prediction (AUC = 0.97, 95% CI 0.78-0.93). CONCLUSIONS: The early diagnosis of PAS in pregnant women requires assessing risk factors, metabolic status, and BS0 levels before 20 weeks of gestation. OMCTS may be related to the development of PAS by promoting trophoblast cell proliferation and migration.

Role of clusterin in the regulation of trophoblast development and preeclampsia.

Preeclampsia (PE) threatens the safety of mothers and fetuses, and its pathogenesis is still unclear. Our previous study has found the relationship between PE and serum Clusterin (CLU). This study aimed to investigate the role of CLU on PE. Firstly, levels of CLU in serum and placental tissue from PE patients and healthy pregnancies were compared. Then, RNA sequencing, cell counting kit-8, matrigel invasion, cell apoptosis, and angiogenesis assay were performed to evaluate the role of CLU on primary isolation trophoblast cells. We found the expression of CLU was increased before the clinical syndrome occurred, whereas its level was positively related to the severity of PE. CLU significantly inhibited the expression of matrix metalloproteinase-9 and Vimentin and enhanced E-cadherin to inhibit epithelial-mesenchymal transition of trophoblast cells, further reducing its migration and invasion. Our results suggested that CLU may play a role in regulating trophoblast invasion and migration during placental development, which may be one of the risk factors for PE.

Early Prediction Model of Gestational Hypertension by Multi-Biomarkers Before 20 Weeks Gestation.

BACKGROUND: Gestational hypertension (GH), a hypertensive disorder of pregnancy (HDP), is a leading cause of maternal and fetal mortality due to the lack of clarity on its exact etiology and clinically feasible prediction models. This study was performed to discover novel biomarkers before 20 weeks gestation and thereby construct an early GH prediction model. METHODS: This study was designed based on differentially expressed protein screening followed by clinical validation. In the screening phase, a nested case-controlled study was conducted by plasma proteomic analyses using label-free LC-MS/MS and plasma samples from seven pre-GH cases before 20-week gestation and seven age- and gestational week-matched controls. In the validation phase, 10 proteins with differential expression in the screening phase were validated by ELISA or electrochemiluminescence in an independent study consisting of 29 pre-GH cases before 20-week gestation and 29 matched controls. RESULTS: In the screening phase, 149 proteins were found to be differentially expressed between the two groups and were predominantly involved in complement and coagulation cascades, platelet degranulation and positive regulation of cell motility. Further validation showed that serpin family C member 1 (SERPINC1), serpin family A member 5 (SERPINA5), complement factor H-related protein 5 (CFHR5), clusterin, cytokeratin 18 (CK18) and histidine-rich glycoprotein (HRG) levels were significantly higher in women who later developed GH compared to women with uncomplicated pregnancies (P<0.05). Binary logistic regression analysis was used to determine the combination efficacy of models for early prediction of GH. The model with a combination of SERPINC1, CK18 and HRG had a significantly better discriminatory power (AUC = 0.91, 95% CI 0.83-0.98) compared to the models with those proteins alone as independent predictors of GH. CONCLUSION: Plasma levels of SERPINC1, SERPINA5, CFHR5, clusterin, CK18 and HRG are potential novel predictive biomarkers of GH, and a prediction model using a combination of SERPINC1, CK18 and HRG has good discriminatory performance for GH before 20 weeks gestation.

Correlation between the positive rate of SAA in children with respiratory tract infection and ambient temperature.

The purpose of this study was to explore the application of serum amyloid A (SAA) in the outcome of upper respiratory tract infection in children by analyzing the correlation between the change of mean air temperature and the positive rate of SAA detection in children. Daily data on upper respiratory tract infection diseases and weather conditions were collected in 2016-2019. A quasi-Poisson regression with a distributed lag non-linear model was used to examine the association between temperature and SAA-positive rate. The positive rate of SAA had a moderate correlation with the temperature and a weak correlation with relative humidity. Low ambient temperature (7 °C, P1) was related to the increase in the positive rate of SAA, with the effect lag for 0-7 days (RR 1.34 (1.19~1.74)). The increase in the SAA-positive case induced by 27 °C (P75) could last for 0-14 days (RR 1.07 (1.01-1.08)), and high temperature (30 °C, P99) could reduce the positive rate of SAA. Our findings add additional evidence to the adverse effects of sub-optimal ambient temperature and provide useful information for public health programs targeting pediatric patients.

Serum complement proteomics reveal biomarkers for hypertension disorder of pregnancy and the potential role of Clusterin.

INTRODUCTION: Hypertension disorder of pregnancy (HDP) is one of the leading causes of maternal and foetal illness. The aim of the current study was to identify and verify novel serum markers for HDP. METHODS: A label-free LC-MS/MS method was used to establish the serum proteomic profiles of 12 pre-HDP (before clinical diagnosis of HDP) pregnancies and verify prioritized candidates in the verification set of 48 pre-HDP pregnancies. These biomarkers were revalidated by ELISA in an independent cohort of 88 pre-HDP pregnancies. Subsequently, the candidate biomarkers were histologically analysed by immunohistochemistry, and function was evaluated in TEV-1 cells. RESULTS: We identified 33 proteins with significantly increased abundance and 14 with decreased abundance (peptide FDR ≤ 1%, P < 0.05). Complement was one of the top enriched components in the pre-HDP group compared with the control group. Three complement factors (CLU, CFHR5, and CRP) were significantly increased in the three sets, of which CLU was a critical factor for the development of HDP (OR = 1.22, P < 0.001). When these three factors and body weight were combined, the AUC was 0.74, with a sensitivity of 0.67 and specificity of 0.68 for HDP prediction compared with normal pregnancy. In addition, inflammation-induced CLU could inhibit the invasion of TEV-1 cells. CONCLUSIONS: Complement proteins may play an essential role in the occurrence of HDP by acting on trophoblast cells. CLU may be a high-risk factor for HDP, and the models combining candidates show reasonable screening efficiency of HDP in the first half of pregnancy.

Gut Microbiota Signatures in Gestational Anemia.

Gestational diseases are associated with altered intestinal microbiota in pregnant women. Characterizing the gut microbiota of gestational anemia (GA) may describe a novel role of gut microbial abnormality in GA. In this study, we investigated differences in gut microbiota between GA patients and healthy pregnant women from the first trimester (n = 24 vs. 54) and the third trimester (n = 30 vs. 56) based on the 16S rRNA gene sequencing method. No statistically significant differences in α-diversity were identified between GA patients and controls in the first trimester of pregnancy, whereas the Shannon index and observed OTUs were significantly lower in GA patients than in healthy controls in the third trimester. Distance-based redundancy analysis revealed striking differences in microbial communities in the third trimester between GA patients and controls. Four genera were significantly different in relative abundance between GA patients and healthy controls, while 12 genera differentiated significantly between GA patients and healthy controls in the third trimester. At the operational taxonomic unit (OTU) level, 17 OTUs and 30 OTUs were identified to be different between GA patients and healthy controls in the first and third trimesters, respectively. Changes in gut microbial composition of GA patients suggest a potential relation with GA, and provide insights into the prediction and intervention of gestational anemia.

Differential expression of serum proteins before 20 weeks gestation in women with hypertensive disorders of pregnancy: A potential role for SH3BGRL3.

INTRODUCTION: The objective of this study was to explore serum levels of differentially abundant proteins between women with hypertensive disorders of pregnancy (HDP) and women with normal-term pregnancy, and to explore the contribution of SH3BGRL3 to the pathogenesis of HDP. METHODS: At 6-20 weeks gestation 48 pregnant women who later developed HDP (HDP group) and 48 women with normal-term pregnancy (normal group) were recruited based on maternal age and gestational age at a 1:1 ratio. Total serum protein was extracted, denatured, deoxidized, and subjected to enzymolysis. The sample was labeled with Tandem Mass Tags and analyzed via mass spectroscopy to identify differentially abundant proteins. The role of SH3BGRL3 in trophoblast invasion, proliferation and apoptosis was examined using the HTR-8/SVneo cell line and primary isolates of extravillous trophoblast (EVT) cells. RESULTS: In the proteomic profiling analysis, there were 19 proteins that showed significant differential abundance (P < 0.05). Among them, 13 proteins were more abundant and 6 proteins were less abundant in the serum from the HDP group compared with the normal group. The function of one of the more abundant proteins, SH3BGRL3, in trophoblast cell invasion, proliferation and apoptosis was investigated. Treatment of the EVT cells or the HTR-8/SVneo cell line with anti-SH3BGRL3 inhibited proliferation, but stimulated both apoptosis and invasion. MMP2 and p-ERK levels were also decreased in EVT after anti-SH3BGRL3 treatment. DISCUSSION: The SH3BGRL3 protein can regulate various aspects of trophoblast biology, and may be useful in the clinical diagnosis of HDP.

The value of microRNAs as the novel biomarkers for colorectal cancer diagnosis: A meta-analysis.

BACKGROUND: Numerous studies have reported that microRNAs (miRNAs) hold great potential as the biomarkers for colorectal cancer (CRC). However, inconsistent results have made it challenging to evaluate their diagnostic performance. Thus, the aim of this meta-analysis was to systematically assess the pooled efficacy of miRNAs for CRC diagnosis. METHODS: A search for eligible studies up to October 30, 2019 was conducted using PubMed, Web of Science and EMBASE databases. A random-effects model was used to evaluate the pooled sensitivity and specificity. The summary receiver operator characteristic (SROC) curve and area under the curve (AUC) were calculated to assess the overall diagnostic efficacy. RESULTS: A total of 3258 CRC patients and 2683 healthy controls were identified in 35 included studies. The overall diagnostic accuracy was as follows: sensitivity, 0.80 [95 % confidence interval (CI) 0.75-0.83]; specificity, 0.80 (95 % CI, 0.75-0.84); positive likelihood ratio (PLR), 4.0 (95 % CI, 3.2-5.0); negative likelihood ratio (NLR), 0.26 (95 % CI, 0.21-0.31); diagnostic odds ratio (DOR), 16 (95 % CI, 11-23); and AUC, 0.87 (95 % CI, 0.83-0.89). CONCLUSION: The results indicated that miRNAs, particularly serum-derived miRNAs, can serve as the powerful and promising biomarkers for early CRC screening.