Down-Regulated JDP2 Attenuated Trophoblast Invasion and Migration in Preeclampsia by Inhibiting Epithelial-Mesenchymal Transition through the Wnt/ß-Catenin Pathway.

INTRODUCTION: Preeclampsia (PE) is an immensely prevalent condition that poses a significant risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast invasion and migration in the context of preeclampsia remains unclear. MATERIALS AND METHODS: The present study aimed to investigate the differential expression of JDP2 between normal control and preeclampsia placentas through the use of quantitative polymerase chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2 on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/ß-catenin pathway. RESULTS: In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison to those of normal placentae. Impairment in migration and invasion was noted upon JDP2 down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin, N-cadherin, and ß-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/ß-catenin signaling was observed as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study. IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells. CONCLUSION: Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in preeclampsia by suppressing the EMT through the Wnt/ß-catenin signaling pathway, thereby offering a potential prognostic and therapeutic biomarker for this condition.

Maternal outcomes of conservative management and cesarean hysterectomy for placenta accreta spectrum disorders: a systematic review and meta-analysis.

BACKGROUND: Cesarean hysterectomy as a traditional therapeutic maneuver for placenta accreta spectrum (PAS) has been associated with serious morbidity, conservative management has been used in many institutions to treat women with PAS. This systematic review aims to compare maternal outcomes according to conservative management or cesarean hysterectomy in women with placenta accreta spectrum disorders. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and four Chinese databases (Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Wanfang database and VIP database) to May 2024. Included studies were to be retrospective or prospective in design and compare and report relevant maternal outcomes according to conservative management (the placenta left partially or totally in situ) or cesarean hysterectomy in women with PAS. A risk ratio (RR) with 95% confidence interval (95% CI) was calculated for categorical outcomes and weighted mean difference (WMD) with 95% CI for continuous outcomes. The Newcastle-Ottawa Quality Assessment Scale was used to assess the observational studies. All analyses were performed using STATA version 18.0. RESULTS: Eight studies were included in the meta-analysis. Compared with cesarean hysterectomy, PAS women undergoing conservative management showed lower estimated blood loss [WMD - 1623.83; 95% CI: -2337.87, -909.79], required fewer units of packed red blood cells [WMD - 2.37; 95% CI: -3.70, -1.04] and units of fresh frozen plasma transfused [WMD - 0.40; 95% CI: -0.62, -0.19], needed a shorter mean operating time [WMD - 73.69; 95% CI: -90.52, -56.86], and presented decreased risks of bladder injury [RR 0.24; 95% CI: 0.11, 0.50], ICU admission [RR 0.24; 95% CI: 0.11, 0.52] and coagulopathy [RR 0.20; 95% CI: 0.06, 0.74], but increased risk for endometritis [RR 10.91; 95% CI: 1.36, 87.59] and readmission [RR 8.99; 95% CI: 4.00, 12.21]. The incidence of primary or delayed hysterectomy rate was 25% (95% CI: 19-32, I2 = 40.88%) and the use of uterine arterial embolization rate was 78% (95% CI: 65-87, I2 = 48.79%) in conservative management. CONCLUSION: Conservative management could be an effective alternative to cesarean hysterectomy when women with PAS desire to preserve the uterus and are informed about the limitations of conservative management. PROSPERO ID: CRD42023484578.

Towards zero excess sludge discharge with built-in ozonation for wastewater biological treatment.

In this study, a biological treatment process, which used a built-in ozonation bypass to achieve sludge reduction, was built to treat the industrial antifreeze production wastewater (mainly composed of ethylene glycol). The results indicated there is a positive correlation between ozone dosage and sludge reduction. At the laboratory level, the MLSS in the system can be stably controlled at around 3400 mg MLSS L-1 under the dosage of 0.18 g O3 g-1 MLSS. Ozonation can increase the compactness of sludge flocs (fractal dimension increased from 1.89 to 1.92). Ozone destroys microbial cell membranes and alters the structure of sludge flocs through direct oxidation through electrophilic reactions. It leads to the release of intracellular polysaccharides, proteins, and other biological macromolecules in microorganisms, thereby promoting the implicit growth of microbial populations. Some bacteria such as g_Pseudomonas, g_Gemmobacter, etc. have strong ethylene glycol degradation ability and tolerance to ozonation. The removal of ethylene glycol includes the glyoxylate cycle, glycine serine carbon cycle, and the glutamate-cysteine ligase pathway of assimilation. Gene KatG and gpx may be key factors in improving microbial tolerance to ozonation. The comprehensive evaluation from the perspectives of cost and carbon emission shows that choosing ozone cracking-implicit growth in wastewater treatment systems has significant cost advantages and application value.

N6-methyladenosine (m6A) Modification in Preeclampsia.

Recently, epitranscriptional modification of N6-methyladenosine (m6A) has received growing attention in the research on the pathogenesis of preeclampsia. Advances in m6A sequencing have revealed the molecular mechanism and importance of m6A modification. In addition, epitranscriptional modification of m6A is closely related to the metabolic processes of placental tissues and cells in preeclampsia. This article reviews the composition, mode of action, and bioinformatics analysis of m6A modification-related proteins, and their biological function in the progression of preeclampsia. The relationship between m6A modification and preeclampsia risk factors, such as diabetes, cardiovascular disease, obesity, and psychological stress, is summarized to provide new ideas for studying PE-targeting molecules.

MYC-targeted genes predict distant recurrence in patients with ocular adnexal extranodal marginal zone lymphoma.

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) is the most frequent subtype of ocular adnexal lymphoma, with a high propensity for recurrence. Distant recurrence (DR) as an essential prognostic event has unique clinical risk factors, but whether distinct molecular features exist remains poorly understood. Here, we identified potential biomarkers using proteomic analysis of 27 OA-EMZL samples. The MYC-targeted genes PCNA, MCM6, and MCM4 were identified as candidates. MYC-targeted genes were further identified as the most significantly activated gene set in patients with DR. The candidate genes were verified in samples from 11 patients with DR and 33 matched controls using immunohistochemistry. The 3-year and 5-year AUC values of MCM6 (0.699 and 0.757) were higher than those of Ki-67 (0.532 and 0.592). High expressions of MCM6 and MCM4 were significantly associated with shorter distant recurrence-free survival (Log-rank p = 0.017, Log-rank p = 0.0053). Multivariate Cox regression identified MCM6 expression as an independent risk factor for DR (HR, 6.86; 95% CI, 1.32-35.79; P = 0.02). Knockdown of c-Myc in B cells resulted in decreased MCM6 and MCM4 expression and reduced proliferative capacity. Our results suggest that activation of the MYC-targeted gene is a distinct molecular feature of DR in OA-EMZL. MYC-targeted gene, MCM6, is a promising pathological biomarker for DR.

Once We Find Grade III Meconium Stained Amniotic Fluid, Must We Act as Early as Possible?

Background: Grade III meconium stained amniotic fluid (MSAF) is a common obstetric disease, and has the greatest impact on poor maternal and neonatal outcomes. Question or Hypothesis or Aim: There is no consensus on treatment, especially on the timing of delivery. Methods: We collected the medical records of 345 women who gave birth with grade III MSAF and analyzed the difference in baseline characteristics and maternal and neonatal outcomes relative to different labor stage, observation times in the first stage of labor, and the presence or absence of abnormal fetal heart rate (FHR) or thick amniotic fluid. Findings: Higher rate of cesarean section was observed when grade III MSAF was found in active labor. Intervention occurred at an observation time of 90-120 min, but there were no significant differences in maternal or neonatal outcomes shown when the observation time was greater than 3 or 4 hours. However, a higher rate of admission to the neonatal intensive care unit was demonstrated in cases with grade III MSAF with abnormal FHR either in the first or second stage of labor or in cases with thick MSAF in the second stage of labor. Discussion: Higher rate of composite adverse neonatal outcomes was found when secondary MSAF (a transition from clear AF to MSAF) was diagnosed >3 h before delivery. Conclusion: In the first stage of labor, an observation time of greater than 4 hours might be possible after grade III MSAF is found if the labor has progressed and is without abnormal FHR.

Aggregation-Induced-Emission Photosensitizer-Loaded Nano-Superartificial Dendritic Cells with Directly Presenting Tumor Antigens and Reversed Immunosuppression for Photodynamically Boosted Immunotherapy.

The success of tumor immunotherapy highlights the potential of harnessing immune system to fight cancer. Activating both native T cells and exhausted T cells is a critical step for generating effective antitumor immunity, which is determined based on the efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells, as well as immunosuppressive reversal. However, strategies for achieving an efficient antigen presentation process and improving the immunosuppressive microenvironment remain unresolved. Here, aggregation-induced-emission (AIE) photosensitizer-loaded nano-superartificial dendritic cells (saDC@Fs-NPs) are developed by coating superartificial dendritic cells membranes from genetically engineered 4T1 tumor cells onto nanoaggregates of AIE photosensitizers. The outer cell membranes of saDC@Fs-NPs are derived from recombinant lentivirus-infected 4T1 tumor cells in which peptide-major histocompatibility complex class I, CD86, and anti-LAG3 antibody are simultaneously anchored. These saDC@Fs-NPs could directly stimulate T-cell activation and reverse T-cell exhaustion for cancer immunotherapy. The inner AIE-active photosensitizers induce immunogenic cell death to activate dendritic cells and enhance T lymphocyte infiltration by photodynamic therapy, promoting the transformation of "cold tumors" into "hot tumors," which further boosts immunotherapy efficiency. This work presents a powerful photoactive and artificial antigen-presenting platform for activating both native T cells and exhausted T cells, as well as facilitating tumor photodynamic immunotherapy.

Maternal and neonatal outcomes of repeated antepartum bleeding in 493 placenta previa cases: a retrospective study.

OBJECTIVE: To explore the effect of antepartum bleeding caused by PP on pregnancy outcomes. STUDY DESIGN: We retrospectively analyzed 493 pregnant women complicated with PP. Patients were divided into antepartum repeated bleeding and non-bleeding groups. Maternal characteristics and pregnancy outcomes were compared. RESULTS: The risk of antepartum hemorrhage was 2.038 times higher when gravidity was 5 (95% CI 1.104-3.760, p = .023). Pregnant women with a history of more than three intrauterine procedures had a 1.968 times higher risk of antepartum hemorrhage (95% CI 1.135-3,412, p = .016) compared to pregnant women without any intrauterine procedures. The risk of antepartum bleeding was found to be decreasing with the pregnancy advancing; When the placenta edge was noted to be over cervical os, the risk of antepartum bleeding was 4.385-fold than the low-lying plcaenta cases (95%CI2.454-8.372, p = .000). In the respect of maternal outcomes, the repeated bleeding group, the risk of emergency surgery was 7.213 times higher than elective surgery (95% CI 4.402-11.817, p = .000). As for the neonatal outcomes, the risk of asphyxia was 2.970 times and the risk of neonatal intensive care unit (NICU) admission was 2.542-fold higher in repeated bleeding group compared to non-bleeding group, respectively. CONCLUSIONS: Obstetricians should be aware of the increased risk of antepartum bleeding especially for ≤34 weeks and placenta edge over cervical os PP patients, they have a higher risk of antepartum bleeding. These women have higher possibility of emergency C-section and need preterm newborn resuscitation.

Emotional responses to mortality salience: Behavioral and ERPs evidence.

Terror Management Theory (TMT) suggests that death-related thoughts activate proximal defense which allows people to suppress or rationalize death awareness. So far there is no direct evidence to support the emotional response in the proximal defense process. The current research aimed to address this issue by examining behavioral (e.g., accuracy and reaction time) and neural responses (e.g., P1 and N400 amplitude) related to emotional arousal following death-related thoughts during proximal defense. Before engaged in emotional words (e.g., anxiety, fear and neutral) judgment task, participants answered questions that referred to emotional and physical changes about death to induce mortality salience (MS). In the control condition, participants received similar instructions concerning the experience of watching TV. Behavioral results showed that longer reaction time of words was seen in control group than MS group. The ERPs results showed that after reminders of death-related thoughts, in condition of MS, fear words elicited larger P1 ERP amplitudes, while the control group did not have this effect, which might reflect that emotional words caused different early attention patterns between MS group and control group. Moreover, compared with control group, larger N400 ERP amplitudes were elicited in condition of MS, suggesting larger cognitive inhibition of words processing caused by emotional reaction. The above results indicate that the early stages after mortality salience will induce fear and anxiety, but soon these negative emotions are suppressed and are at a lower level of accessibility. This result provides electrophysiological evidence for the proximal defense hypothesis of terror management theory.

Aspirin reduces sFlt-1-mediated apoptosis of trophoblast cells in preeclampsia.

Preeclampsia (PE) is a hypertensive disorder that occurs during pregnancy. Low-dose aspirin is used to reduce the occurrence of early-onset PE; however, the mechanisms are not clear. The aim of this study was to reveal the underlying mechanism of aspirin in reducing sFlt-1-mediated apoptosis of trophoblast cells in PE. Serum sFlt-1 and sEng profiles and placental oxidative stress levels were significantly decreased in PE patients treated with aspirin compared with untreated patients without it, whereas serum PLGF and placental SOD profiles were increased in PE patients with aspirin. Aspirin attenuated the role of sFlt-1 in oxidative stress and endothelial dysfunction and reduced apoptosis of trophoblasts by inactivating the NF-κB signalling pathway in HTR-8/SVneo trophoblast cells. Blood pressure, urine protein, swelling of the villous vessels and mitochondrial parameters were noted to be much better after aspirin administrated to sFlt-1 treated pregnant mice. In conclusion, aspirin reverses the endothelial dysfunction and oxidative stress caused by sFlt-1 and thus reduces apoptosis of preeclamptic trophoblasts by inactivating NF-κB signalling pathway.

Advances in the Detection of Pancreatic Cancer Through Liquid Biopsy.

Pancreatic cancer refers to the development of malignant tumors in the pancreas: it is associated with high mortality rates and mostly goes undetected in its early stages for lack of symptoms. Currently, surgical treatment is the only effective way to improve the survival of pancreatic cancer patients. Therefore, it is crucial to diagnose the disease as early as possible in order to improve the survival rate of patients with pancreatic cancer. Liquid biopsy is a unique in vitro diagnostic technique offering the advantage of earlier detection of tumors. Although liquid biopsies have shown promise for screening for certain cancers, whether they are effective for early diagnosis of pancreatic cancer is unclear. Therefore, we reviewed relevant literature indexed in PubMed and collated updates and information on advances in the field of liquid biopsy with respect to the early diagnosis of pancreatic cancer.

Pubescenosides Q-R, two new phenolic glycosides from Ilex pubescens.

Two new phenolic glycosides (1-2), along with six existing compounds (3-8), were isolated from the ethanolic extract of Ilex pubescens roots, a traditional folk medicine. These structures were determined using HR-ESI-MS, IR, UV, and NMR (including 1 D, 2 D-NMR). The anti-inflammatory activities of three phenolic glycosides (1-3) were evaluated in the human HepG2 cell lines. The results showed that compound 3 could induce P-gp and BCRP expression through the Nrf2-mediated pathway.[Formula: see text].

LncRNA MALAT1 affects the migration and invasion of trophoblast cells by regulating FOS expression in early-onset preeclampsia.

BACKGROUND: Preeclampsia (PE), particularly early-onset PE (ePE), causes maternal and fetal complications and remains a major health problem in modern society. Aberrant uterine spiral artery remodeling leads to ePE through poor placentation. In this study, we investigated the role of the long non-coding RNA (lncRNA) MALAT1 in ePE pathogenesis. METHODS: Total RNA was extracted from 40 paired placental ePE tissues and control groups. RNA levels were quantified by qRT-PCR and protein expression was determined by western blotand immunohistochemistry (IHC) analysis. The effects of MALAT1 on trophoblast migration and invasion were evaluated in HTR-8/SVneo and JAR cells. FOS was identified as a downstream functional gene of MALAT1 by RNA-seq. RNA binding protein immunoprecipitations (RIPs) were performed to reveal the cellular targets of MALAT1. RESULTS: MALAT1 was poorly expressed in ePE placentas and its silencing (-/-) inhibited trophoblast invasion and migration. MALAT1 -/- also decreased N-cadherin and vimentin expression, but increased E-cadherin expression. RNA-seq analysis and subsequent RIP assays showed that MALAT1 improved FOS through Hu-antigen R (HuR) binding. FOS overexpression similarly enhanced trophoblast migration and invasion. IHC staining showed that E-cadherin was upregulated in placenta tissue from ePE groups, whilst FOS, N-cadherin, and vimentin were downregulated. CONCLUSION: MALAT1 promotes trophoblast migration and invasion through FOS-induced epithelial mesenchymal transition (EMT). This highlights new roles for MALAT1 in the impairment of spiral artery remodeling in ePE pathogenesis.

Multi-resolution convolutional networks for chest X-ray radiograph based lung nodule detection.

Lung cancer is the leading cause of cancer death worldwide. Early detection of lung cancer is helpful to provide the best possible clinical treatment for patients. Due to the limited number of radiologist and the huge number of chest x-ray radiographs (CXR) available for observation, a computer-aided detection scheme should be developed to assist radiologists in decision-making. While deep learning showed state-of-the-art performance in several computer vision applications, it has not been used for lung nodule detection on CXR. In this paper, a deep learning-based lung nodule detection method was proposed. We employed patch-based multi-resolution convolutional networks to extract the features and employed four different fusion methods for classification. The proposed method shows much better performance and is much more robust than those previously reported researches. For publicly available Japanese Society of Radiological Technology (JSRT) database, more than 99% of lung nodules can be detected when the false positives per image (FPs/image) was 0.2. The FAUC and R-CPM of the proposed method were 0.982 and 0.987, respectively. The proposed approach has the potential of applications in clinical practice.

Intrapartum Results on Differing Degrees of Ketonuria in Nulliparous Women with Gestational Diabetes Mellitus during Spontaneous Labor.

To compare intrapartum results associated with differing degrees of ketonuria in nulliparous women with gestational diabetes mellitus (GDM), we implemented a retrospective cohort study comparing clinical characteristics among differing degrees of ketonuria and the duration and distribution of ketonuria at different stages of labor. We also analyzed adverse maternal and neonatal outcomes for each group. A total of 570 GDM deliveries were included; of these, 238 had negative ketonuria (41.8%), 180 had moderate ketonuria (31.6%), and 152 had ketosis (26.6%). The proportion of patients with a family history of diabetes significantly increased as the degree of ketonuria increased (P < 0.001). Moreover, a significantly lower level of HOMA-IR (the insulin resistance index) was observed for the Negative group (P < 0.001). The triglyceride (TG) level was significantly higher in the Ketosis group (P < 0.001), and the total cholesterol (TC) levels significantly increased as the degree of ketonuria progressed (P < 0.001). There were also higher maternal blood sugar levels and a significantly higher proportion of oxytocin augmentation in ketonuria cases (P < 0.001). Over three-fourths of patients (75.6%) had a ketonuria duration of ≤2 hours in the Moderate group, 61.2% had a ketonuria duration of between 3 and 4 h in the Ketosis group, and most of the ketonuria cases resolved in the first stage of labor. As the degree of ketonuria progressed, we observed a significantly higher number of cases with fetal heart rate pattern III (FHR pattern III), meconium-stained amniotic fluid III (MSAF III), postpartum hemorrhages, prolonged labor, neonatal hypoglycemia, an umbilical cord arterial pH of <7.2, low Apgar scores, increased neonatal intensive care admissions, augmented forceps-assisted deliveries, and conversions to cesarean sections. The results showed that ketonuria is common during the intrapartum period and that the risk of adverse maternal and neonatal outcomes may increase when complicated with ketonuria.

The neural correlate of mid-value offers in ultimatum game.

In the ultimatum game (UG), mid-value offers are unfair but not so unreasonable as to be rejected immediately. As a consequence, they are difficult for responders to evaluate because of the conflict that arises between two key processes, namely inequity aversion and self-interests. Since there is no clear consensus in the literature on event-related potential (ERP) as to how mid-value offers are processed, we designed an experiment to explore how the ability to reject offers influences key ERP signatures. By manipulating the right to reject offers based on game type (ultimatum game, UG or dictator game, DG), our study explored how ERPs were influenced by three types of offers available to participants (fair, unfair and mid-value). We recorded the electroencephalogram results of 28 participants while they responded to the three kinds of offers in the UG and the DG. We observed that mid-value offers in the UG elicited more negative feedback-related negativity and N400 than did the unfair offers. However, these ERP patterns were specific to the UG. Furthermore, we interpreted these results as further electrophysiological evidence of the interaction between the two processing systems during the UG.

Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE.

The long noncoding RNA HOXA11-AS displays abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in preeclampsia (PE). In this study, we report that HOXA11-AS is significantly downregulated in preeclamptic placental tissues and could contribute to the occurrence and development of PE. Silencing of HOXA11-AS expression could significantly suppress trophoblast cell growth and migration, whereas HOXA11-AS overexpression facilitated cell growth in the HTR-8/SVneo, JEG3, and JAR cell lines. RNA-seq analysis also indicated that HOXA11-AS silencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed that HOXA11-AS could recruit Ezh2 and Lsd1 protein and regulate RND3 mRNA expression in the nucleus. In the cytoplasm, HOXA11-AS modulates HOXA7 expression by sponged miR-15b-5p, affecting trophoblast cell proliferation. Together, these data confirm that aberrant expression of HOXA11-AS is involved in the occurrence and development of PE and may act as a prospective diagnosis and therapeutic target in PE.

Long Noncoding RNA 00473 Is Involved in Preeclampsia by LSD1 Binding-Regulated TFPI2 Transcription in Trophoblast Cells.

Preeclampsia (PE) is a syndrome manifested by high blood pressure that could develop in the latter half of pregnancy; however, the underlying mechanisms are not understood. Recent evidence points to the function of noncoding RNAs (ncRNAs) as novel regulators of the invasion, migration, proliferation, and apoptosis of trophoblasts involved in the development of placental vasculature. Here, we investigated the role of long intergenic ncRNA 00473 (linc00473) in PE and the associated molecular mechanisms. The expression of linc00473 was downregulated in the placenta of patients with severe PE as revealed by qRT-PCR analysis. In vitro, linc00473 knockdown in trophoblast cell lines HTR-8/SVneo, JAR, and JEG3 significantly inhibited cell proliferation and promoted apoptosis, whereas linc00473 overexpression stimulated trophoblast proliferation. The mechanistic insights were provided by RNA-seq and qRT-PCR, which revealed that linc00473 could regulate the transcription of genes relevant to cell growth, migration, and apoptosis. In particular, linc00473 inhibited the expression of tissue factor pathway inhibitor 2 (TFPI2) through binding to lysine-specific demethylase 1 (LSD1). These results indicate that linc00473 could be involved in the pathogenesis and development of PE and may be a candidate biomarker as well as therapeutic target for this disease.

Patients with Unexplained Recurrent Spontaneous Abortion Show Decreased Levels of Microrna-146a-5p in the Deciduae.

BACKGROUND: Immune intolerance of the fetal-placental unit may be a contributing cause of unexplained recurrent spontaneous abortion (URSA). OBJECTIVES: This study is to investigate the relevance of the miR-146a-5p/IFN-γ pathway to URSA. MATERIAL AND METHODS: Quantitative real-time RT-PCR and western blot were performed to compare the levels of miR-146a-5p, IFN-γ, IRAK1, and TRAF6 in the deciduae of URSA (n=29) and healthy women (n=35) after an elective abortion. RESULTS: The levels of miR-146a-5p were lower in the deciduae of patients with URSA compared with control subjects (P=0.027). The mRNA and protein expressions of IFN-γ, IRAK1, and TRAF6 were higher in the deciduae in patients with URSA compared with control subjects (P<0.05). There were negative correlations between the miR-146a-5p level and the levels of IRAK1 and TRAF6 mRNAs. The protein levels of IFN-γ, IRAK1, and TRAF6 positively correlated with each other (P<0.01). CONCLUSION: Low miR-146a-5p may promote the activity of IFN-γ, subsequently leading to immune intolerance of the fetal-placental unit, which may contribute to URSA.

The long non-coding RNA PVT1 represses ANGPTL4 transcription through binding with EZH2 in trophoblast cell.

Despite progress in diagnostics and treatment for preeclampsia, it remains the foremost cause of maternal and foetal perinatal morbidity and mortality worldwide. Over recent years, various lines of evidence have emphasized long non-coding RNAs (lncRNAs) which function as an innovative regulator of biological behaviour, as exemplified by proliferation, apoptosis and metastasis. However, the role of lncRNAs has not been well described in preeclampsia. Here, we identified a lncRNA, PVT1, whose expression was down-regulated in qRT-PCR analyses in severe preeclampsia. The effects of PVT1 on development were studied after suppression and overexpression of PVT1 in HTR-8/SVneo and JEG3 cells. PVT1 knockdown notably inhibited cell proliferation and stimulated cell cycle accumulation and apoptosis. Exogenous PVT1 significantly increased cell proliferation. Based on analysis of RNAseq data, we found that PVT1 could affect the expression of numerous genes, and then investigated the function and regulatory mechanism of PVT1 in trophoblast cells. Further mechanistic analyses implied that the action of PVT1 is moderately attributable to its repression of ANGPTL4 via association with the epigenetic repressor Ezh2. Altogether, our study suggests that PVT1 could play an essential role in preeclampsia progression and probably acts as a latent therapeutic marker; thus, it might be a useful prognostic marker when evaluating new therapies for patients with preeclampsia.