MicroRNA-30a-3p is overexpressed in the placentas of patients with preeclampsia and affects trophoblast invasion and apoptosis by its effects on IGF-1.

OBJECTIVE: Preeclampsia (PE) affects many women globally and remains a primary cause of neonatal and maternal morbidity and mortality. Aberrant placental microRNA (miRNA) expression might be associated with PE. Previously, 33 PE-related miRNAs, 11 up-regulated and 23 down-regulated, were detected in placentas of women with severe PE when compared with those of normal patients. One of the most up-regulated miRNAs in PE is miR-30a-3p. The predicted target of it is insulin-like growth factor 1 (IGF-1), which has been reported to have a relatively low expression level in PE patients. This study was conducted to determine the aberrant increased of miR-30a-3p in the placentas of women with preeclampsia and to elucidate the target and function of it in trophoblast cells. STUDY DESIGN: miR-30a-3p expression in placenta tissues was compared between women with preeclampsia (n = 25) and normal pregnant women (n = 20). The miRNA target was studied by in silico and functional assay. The effects of the miRNA were verified by apoptosis assay and invasion assay in the trophoblast cell line. RESULTS: miR-30a-3p was increased significantly in the placenta of women with preeclampsia when compared to those with normal pregnancies. Luciferase assay confirmed direct regulation of miR-30a-3p on the expression of IGF-1. Forced expression of miR-30a-3p suppressed IGF-1 protein expression in the HTR-8/SVneo cells. The functional assay suggests that the over-expression of miR-30a-3p alter the invasive capacity of JEG-3 cells and induce the apoptosis of HTR-8/SVneo cells (Figure). CONCLUSION: Expression of miR-30a-3p was significantly increased in the placentas of patients with preeclampsia. miR-30a-3p might be involved in the pathogenesis of preeclampsia by targeting IGF-1 and regulating the invasion and apoptosis of trophoblast cells.

FAM3A Protects Against Glutamate-Induced Toxicity by Preserving Calcium Homeostasis in Differentiated PC12 Cells.

BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells. The protective effects were determined by measuring lactate dehydrogenase (LDH) release, apoptosis and mitochondrial oxidative stress. Ca2+ imaging was performed to detect changes in intracellular Ca2+ concentration in PC12 cells. The related molecular mechanisms were investigated by fluorescence staining, coimmunoprecipitation (Co-IP) and western blotting. RESULTS: Upregulation of FAM3A by lentivirus transfection markedly decreased LDH release, inhibited apoptosis and reduced mitochondrial oxidative stress, which were accompanied by alleviated intracellular Ca2+ levels as measured by calcium imaging. The results of western blotting showed that FAM3A significantly decreased the surface expression of metabotropic glutamate receptor 1/5 (mGluR1/5), with no effect on the expression of N-methyl-d-aspartic acid receptor (NMDAR) or α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunits. FAM3A overexpression also inhibited the intracellular Ca2+ release mediated by mGluR1/5 and inositol 1,4,5-trisphosphate receptor (IP3R), but not the ryanodine receptor (RyR). In addition, FAM3A significantly attenuated the store-operated calcium entry (SOCE) induced by thapsigargin (Tg), but the expression of SOCE-related proteins was not altered. The results of coimmunoprecipitation (Co-IP) showed that FAM3A disrupted the interaction of stromal interaction molecule 1 (STIM1) with Orai1 triggered by glutamate. CONCLUSION: These results suggest that the upregulation of FAM3A protects against glutamate-induced dysfunction of Ca2+ homeostasis not only by inhibiting mGluR1/5-dependent endoplasmic reticulum (ER) Ca2+ release, but also by attenuating SOCE mediated by the STIM1-Orai1 interaction.

FAM3A Protects HT22 Cells Against Hydrogen Peroxide-Induced Oxidative Stress Through Activation of PI3K/Akt but not MEK/ERK Pathway.

BACKGROUND/AIMS: Oxidative stress-induced cell damage is involved in many neurological diseases. FAM3A is the first member of family with sequence similarity 3 (FAM3) gene family and its biological function remains largely unknown. METHODS: This study aimed to determine its role in hydrogen peroxide (H2O2) induced injury in neuronal HT22 cells. The protective effects were measured by cell viability, lactate dehydrogenase (LDH) release and apoptosis, and oxidative stress was assayed by reactive oxygen species (ROS) generation, ATP synthesis and lipid peroxidation. By using selective inhibitors, the involvement of PI3K/Akt and MEK/ERK pathways were also investigated. RESULTS: The results of fluorescence staining revealed that H2O2 significantly decreased the expression of FAM3A protein, which was shown to be subcellularly located in mitochondria. Up-regulation of FAM3A by lentivirus transfection markedly increased cell viability and decreased LDH release after H2O2 treatment. The anti-apoptotic activity of FAM3A was demonstrated by the reduced mitochondrial cytochrome c release, decreased activation of caspase-3 and the results of flow cytometry. Overexpression of FAM3A attenuated intracellular ROS generation and loss of ATP production induced by H2O2, and subsequently inhibited lipid peroxidation. In addition, overexpression of FAM3A significantly increased the activation of Akt and ERK in H2O2 injured HT22 cells. By using Akt and ERK specific inhibitors, we found that inhibition of PI3K/Akt, but not MEK/ERK pathway, partially prevented FAM3A-induced protection against H2O2. CONCLUSION: These results suggest that FAM3A has protective effects against H2O2-induced oxidative stress by reducing ROS accumulation and apoptosis, and these protective effects are dependent on the activation of PI3K/Akt pathway.

Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis.

The chemokine CXCL12 and its receptor CXCR4 are important signaling components required for human blastocyst implantation and the progression of pregnancy. Growing evidence indicates that the CXCL12/CXCR4 axis can regulate trophoblast function and uterine spiral artery remodeling, which plays a fundamental role in placentation and fetal outcome. The orphan receptor CXCR7 is also believed to partly regulate the function of the CXCL12/CXCR4 axis. Additionally, the CXCL12/CXCR4/CXCR7 axis can enhance the cross-talk between trophoblasts and decidual cells such as uterine natural killer cells and decidual stromal cells which are involved in regulation of trophoblast differentiation and invasion and placental angiogenesis. In addition, recent studies proved that CXCL12 expression is elevated in the placenta and mid-trimester amniotic fluid of pregnant women with preeclampsia, implying that dysregulation of CXCL12 plays a role in the pathogenesis of preeclampsia. Further understanding of the regulatory mechanisms of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis may help to design novel therapeutic approaches for pregnancy-associated diseases.

Identification and verification of diagnostic biomarkers based on mitochondria-related genes related to immune microenvironment for preeclampsia using machine learning algorithms.

Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Preeclampsia is linked to mitochondrial dysfunction as a contributing factor in its progression. This study aimed to develop a novel diagnostic model based on mitochondria-related genes(MRGs) for preeclampsia using machine learning and further investigate the association of the MRGs and immune infiltration landscape in preeclampsia. In this research, we analyzed GSE75010 database and screened 552 DE-MRGs between preeclampsia samples and normal samples. Enrichment assays indicated that 552 DE-MRGs were mainly related to energy metabolism pathway and several different diseases. Then, we performed LASSO and SVM-RFE and identified three critical diagnostic genes for preeclampsia, including CPOX, DEGS1 and SH3BP5. In addition, we developed a novel diagnostic model using the above three genes and its diagnostic value was confirmed in GSE44711, GSE75010 datasets and our cohorts. Importantly, the results of RT-PCR confirmed the expressions of CPOX, DEGS1 and SH3BP5 were distinctly increased in preeclampsia samples compared with normal samples. The results of the CIBERSORT algorithm revealed a striking dissimilarity between the immune cells found in preeclampsia samples and those found in normal samples. In addition, we found that the levels of SH3BP5 were closely associated with several immune cells, highlighting its potential involved in immune microenvironment of preeclampsia. Overall, this study has provided a novel diagnostic model and diagnostic genes for preeclampsia while also revealing the association between MRGs and immune infiltration. These findings offer valuable insights for further research and treatment of preeclampsia.

Length of stay in the ward following a preeclamptic pregnancy.

To date, data on postpartum management of preeclampsia including the optimal time for discharge are limited. The aims of this study were to investigate the appropriate time for discharge after delivery, and factors that could affect the time for discharge. Data on 210 preeclamptic women including the severity or time of onset and days in the ward after delivery were collected and analysed. In total, 167 (73%) patients were followed up for at least 16 months and none of them developed any complications after delivery. The mean days in the ward after delivery in preeclamptic women with vaginal delivery or with caesarean section was 3.4 or 5.8 days, respectively. After adjusting for delivery modes and parity, women with severe or early onset preeclampsia or preeclamptic women complicated with IUGR were in the ward longer than women with mild or late onset of preeclampsia or preeclamptic women without IUGR. In addition, women with severe preeclampsia or with IUGR delayed the time for blood pressure to return to normal range. Our descriptive data reported that preeclamptic women stayed in the ward for 4-6 days after delivery, dependent on the delivery modes. Preeclamptic women with severe or early onset form or complicated with IUGR delayed the improvement of clinical symptoms after delivery. We further found that women with severe preeclampsia, and preeclampsia complicated with IUGR delayed blood pressure returning to normal range. These pre-discharge checklists may help obstetricians and midwives decide when to discharge.

Landscape of somatic alterations in large-scale solid tumors from an Asian population.

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.

Short-Term Prediction of Preeclampsia in Chinese Women Using the Soluble fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio: A Sub-Analysis of the PROGNOSIS Asia Study.

The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n = 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to delivery. The overall prevalence of preeclampsia was 17.3%. With the use of an sFlt-1/PlGF ratio of ≤38, the negative predictive value for ruling out preeclampsia within 1 week was 97.3% [95% confidence interval (CI), 93.8-99.1], with a sensitivity of 64.3% and specificity of 85.3%. With the use of an sFlt-1/PlGF ratio of >38, the positive predictive value for ruling in preeclampsia within 4 weeks was 35.0% (95% CI, 20.6-51.7), with a sensitivity of 50.0% and specificity of 86.8%. In the analyses of the sFlt-1/PlGF ratio and fetal adverse outcomes, the area under the receiver operating characteristic curve was 92.8% (95% CI, 83.5-98.7) for ruling out fetal adverse outcomes within 1 week and 79.9% (95% CI, 68.1-90.3) for ruling in fetal adverse outcomes within 4 weeks. An sFlt-1/PlGF ratio of >38 increased the likelihood of imminent delivery 3.3-fold compared with a ratio of ≤38 [hazard ratio, 3.3 (95% CI, 2.1-5.1)]. This sub-analysis confirms the high predictive performance of the sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia in Chinese women, which may help prevent unnecessary hospitalization of women with low risk of developing preeclampsia.

[Early glucose challenge test in pregnant women with risk factors of GDM in China].

OBJECTIVE: To understand the current status and clinical relevance of early (<24 weeks) glucose challenge test (GCT) in pregnant women with risk factors of gestational diabetes mellitus (GDM) in China. METHODS: Data from the survey of incidence of GDM in China were re-analyzed. The incidence of abnormal glucose metabolisms and the rate of early GCT in all women were calculated according to different numbers of risk factors. Sixteen risk factors were included in the survey. However, 4 independent risk factors were considered separately in this re-analysis. The ADA criteria for GDM diagnosis were applied. RESULTS: A total of 16 286 pregnant women were included in this analysis and 64.3% (10 468) presented with at least one risk factor. The incidence of GDM became elevated with the increasing number of risk factors (P < 0.001). Early GCT was performed in 1687 (16.1%) pregnant women and the early detected GDMs only accounted for 11.9% of all GDMs among those with at least one risk factor. Among those who had early GCT, the GDM diagnosis rate increased with the number of risk factors (P < 0.001). Previous analysis in this survey identified 4 independent risk factors for GDM among 16 risk factors: BMI > or = 24, age over 30 years old, family history of DM and southerners. Similar analysis was performed according to the above 4 risk factors and similar results were found as those found for 16 risk factors. No significant difference was found in the GDM and GIGT incidence between the two analyses in those with at least one risk factor. CONCLUSION: Early GCT is necessary for pregnant women with risk factors of GDM, but the screening rate in China is low. GCT should be repeated for those women with risk factors of GDM and normal GCT at early screening.

[Effect of integrative Chinese and Western medicine in treating pregnant women with intrahepatic cholestasis].

OBJECTIVE: To evaluate the therapeutic effect of compound salvia injection combined with ursodeoxycholic acid (UDCA) in treating pregnant women with intrahepatic cholestasis (ICP) and its influence on perinatal babies. METHODS: One hundred and twenty-eight patients of ICP were assigned to two groups. The 72 patients in the treatment group were treated with salvia injection (20 mL in 10% glucose 500 mL for intravenous dripping once a day) and UDCA (15 mg, thrice daily by oral taken), and the 56 patients in the control group were treated with UDCA alone, all were treated for 14 days. Changes of itching symptom (estimated by scoring) and serum levels of biochemical indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (TBil) and glycocholic acid (GCA), were determined before and after treatment, and conditions of the newborns were compared after delivery. RESULTS: Compared with before treatment, scores of itching were lowered from 3.6 scores to 1.4 scores in the treatment group, and from 3.4 scores to 1.6 scores in the control group, showing no significant difference between groups (P > 0.05), but the lowering was shown earlier in the former. Levels of biochemical indexes were improved significantly (P < 0.01) in both groups, but the improvements were more significant in the treatment group, the difference between groups was significant (P < 0.05). The difference between groups in the incidence of fetal distress, meconium-stained fluid and neonatal asphyxia were insignificant (P > 0.05). The birth weights of the newborns were higher in the treatment group than in the control group (3,108 +/- 236 g vs 2,681 +/- 269 g, P < 0.05). CONCLUSION: The combined therapy of compound salvia injection and UDCA shows better effect in treating ICP than that of UDCA alone.

[Investigation on treatment of fetal growth restriction by salvia injection combined with composite amino acid].

OBJECTIVE: To explore the effect of salvia injection (SI) combined with composite amino acid (CAA) in treating fetal growth restriction (FGR). METHODS: A retrospective analysis was conducted on 106 pregnant women with FGR hospitalized from January 2007 to January 2008. Patients were randomized into 2 groups equally, the treated group (53 cases) treated with SI plus CAA, and the control group treated with CAA alone, all for 7 days. The clinical effect and umbilical blood flow (S/D) in patients were observed. RESULTS: (1) The total effective rate in the treated group was 81.13%, it was 88.80% (16/18) for patients in the gestation period of 24+ -28 weeks, 80.00% (12/15) for those of 28+ -32 weeks, and 75.00 (15/20) for 32+ -36 weeks, while in the control group, the corresponding rates were 69.81%, 77.77% (14/18), 66.66% (10/15), and 65.00% (13/20), respectively. The difference between the two groups was significant (P < 0.05). (2) After treatment, S/D significantly lowered in patients of the treated group (P < 0.05, P < 0.01), no matter how long the gestation period was, but it was insignificantly changed in the control group. CONCLUSION: The combined treatment with SI and CAA on FGR could improve the condition of the fetus.

Expectant or outpatient management of preeclampsia before 34 weeks: safe for mother but associated with increased stillbirth risk.

Today the only effective "treatment" for preeclampsia is to deliver at the optimal time for both maternal and foetal well-being. Studies reported that severe preeclampsia can benefit from the expectant management including mild preeclampsia between 34 and 37 weeks. However it is unclear whether mild preeclampsia before 34 weeks also benefits from the expectant management. Data on 274 women with mild preeclampsia before 37 weeks of gestation were retrospectively collected and analysed. Blood pressure and proteinuria at time of onset were not clinically associated with delivery time. For women who developed preeclampsia before 34 weeks, the median latency from onset to delivery or from onset to admission to hospital or from admission to hospital to delivery was 27 or 21 or 3 days, respectively. There were four women (2%) who delivered within 48 h after onset, 28 (14%) FGR and 14 (7%) stillbirths. The median birth-weight was 2240 g. For women who developed preeclampsia between 34 and 37 weeks, the median latency from onset to delivery or from onset to admission to hospital or from admission to hospital to delivery was 11 or 7 or 2 days, respectively. There were seven women (10%) who delivered within 48 h after onset and eight (12%) FGR. The median birth-weight was 2880 g. Our study demonstrates that mild preeclampsia before 37 weeks has benefits from expectant or outpatient management with a median prolongation of over 11 days dependent on the time of onset, but it increases the risk for stillbirths before 34 weeks.

[Impact of fetal growth restriction on spatial learning and memory abilities of the offspring of rats].

OBJECTIVE: To test the impact of fetal growth restriction (FGR) on the spatial learning and memory abilities of the offspring of rats. METHODS: FGR Model of Sprague-Dawley rats was constructed according to the method of passive smoking. The offspring of the rats were divided into male FGR group, male control group, female FGR group and female control group. Within each group, the rats were randomly divided into three subgroups to be tested at 1, 2, and 4 months of age, respectively (n =10 for each subgroup). Morris water maze task was performed to assess the spatial learning and memory abilities of the rats. RESULTS: The escape latencies to find the platform were shortened with increased training times for all of the rats. At the age of 1 and 2 months, both male and female rats in the FGR group spent more time in finding the platform than their counterparts in the control group (P < 0.05). At the age of 4 months, significant prolonged latency was only found in the female rats. The rats in the FGR group, except the 4 months old male rats, were more likely to use non-effective strategies (random or marginal strategies) to find the platform than the efficient strategies (tendency or straight strategies). The rats in the FGR group stayed in the platform shorter than those in the control groups (P < 0.05). CONCLUSION: FGR can cause gender- and age-specific impairment of spatial learning and memory abilities to the offspring.

Zinc improves learning and memory abilities of fetal growth restriction rats and promotes trophoblast cell invasion and migration via enhancing STAT3-MMP-2/9 axis activity.

Fetal growth restriction (FGR) is a well-known risk factor for cognitive dysfunction, especially for learning and memory abilities. However, knowledge about prevention and treatment methods of learning and memory abilities of fetal are limit. Here, Morris water maze and passive avoidance tests showed zinc supplementation could protect the impairment of the learning and memory abilities caused by FGR. As accumulating evidence suggested that insufficiency of placental trophoblast cell invasion was closely related to FGR fetal neurodevelopmental dysplasia, we further explored the relationship between zinc supplementation during pregnancy and placental trophoblast. Microarray identified 346 differently expressed genes in placental tissues with and without zinc supplementation, and GO and KEGG analyses showed these differently expressed genes were highly enriched in cell invasion and migration and STAT3 pathway. Protein-protein interaction(PPI) analysis found that STAT3 interacted with matrix metalloproteinase-2/9 (MMP-2/9). In vivo, western blot results authenticated that the expression levels of phospho-STAT3, STAT3, MMP-2 and MMP-9 were up-regulated in placental tissues after zinc treatment. To validate whether zinc could promotes trophoblast cell invasion and migration via enhancing STAT3-MMP-2/9 activity. In vitro, Transwell assay was performed, and we observed that abilities of invasion and migration were obviously increased in zinc treated trophoblast cells. And phospho-STAT3, STAT3, MMP-2 and MMP-9 expression levels were correspondingly increased in zinc treated trophoblast cells, which were dose-dependent. Moreover, gain-of-function and loss-of-function of STAT3 confirmed that zinc promotes cell invasion and migration via regulating STAT3 mediated up-regulation of MMP-2/9 activity. We propose that activation of MMP-2/9 mediated by STAT3 may contribute to invasion and migration of trophoblast cells, which improved neurodevelopmental impairment of FGR rats probably via contributing to placental development. Our findings are the first to show a possible mechanism of reversing neurodevelopmental impairment of FGR rats by zinc supplementation, holding promise for the development of novel therapeutic modalities for learning and memory abilities impairment caused by FGR.

Proteinuria in preeclampsia: Not essential to diagnosis but related to disease severity and fetal outcomes.

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality globally and proteinuria can be one of the cardinal features of this disease. However, studies about the association of the amount of proteinuria and the severity of preeclampsia, and perinatal outcomes are limited. Data on 239 women with preeclampsia were retrospectively collected from a university teaching hospital from September 2011 to June 2013 and analysed. Data included all clinical parameters and proteinuria in a 24h urine collection. In cases of severe preeclampsia, significantly fewer patients had proteinuria levels <0.3g/L in comparison to any of the other groups with proteinuria >0.3g/L, but there was no difference in cases of severe preeclampsia when proteinuria levels were >0.3g/L. Furthermore, when proteinuria levels were >0.3g/L, the frequency of severe preeclampsia in each group was significantly higher than the frequency of mild pre-eclampsia cases. Time of onset was significantly earlier in patients with proteinuria >3g/L in a 24h urine collection, but time between the onset of preeclampsia and delivery was not correlated with the amount of proteinuria. The birth weight was significantly lower in patients with proteinuria >3g/L. The incidence of fetal growth restriction or stillbirth was significantly higher in patients with proteinuria >5g/L. Our data demonstrate that the amount of proteinuria is not associated with the severe of preeclampsia, once proteinuria is detected, but is related to the severity of preeclampsia. The adverse fetal outcomes appear to be the function of prematurity rather than proteinuria itself.

Autoantibodies against glucose-regulated protein 78 as serological biomarkers in metastatic and recurrent hepatocellular carcinoma.

PURPOSE: To identify Heptocellular carcinoma (HCC) associated antigens by proteomics, and validate whether autoantibodies against tumor-associated antigens (TAAs) could be used for diagnosis and conditional monitoring. RESULTS: The 78 kDa glucose regulated protein (GRP78) was selected as a candidate TAA. The titers of autoantibodies against 78 kDa glucose regulated protein (GRP78) from patients with HCC, liver cirrhosis (LC), and chronic hepatitis (CH) were significantly higher than that from normal controls (P<0.05, P<0.001, and P<0.01, respectively). The expression of autoantibodies against GRP78 was associated with clinical stage (P<0.01), portal vein invasion (P<0.05), and metastasis (P<0.05). The expression of anti-GRP78 antibodies was significantly higher 1 month after surgery in recurrent patients who had accepted hepatic resection 1 month after surgery compared to patients who had surgery before surgery or within 1 week after surgery (P<0.01 and P<0.001). Immunohistochemistry (IHC) showed higher expression of GRP78 in HCC compared to the non-HCC liver tissues (P <0.05). MATERIALS AND METHODS: HCC serum with high titer of autoantibodies against TAAs were screened and used for a proteome-based approach to identify HCC associated antigens. Indirect enzyme-linked immunoassay (ELISA) was used to detect the corresponding autoantibodies against TAAs. CONCLUSION: GRP78 is an autoantigen that could stimulate autoimmune responses and serve as a potential marker for recurrent and metastatic progression in HCC.

FAM3A attenuates ER stress-induced mitochondrial dysfunction and apoptosis via CHOP-Wnt pathway.

Endoplasmic reticulum (ER) stress is linked to several neurological disorders, and neuronal injury cascades initiated by excessive ER stress are mediated, in part, via mitochondrial dysfunction. In the present study, we identified FAM3A as an important regulator of ER stress-induced cell death in neuronal HT22 cells. The ER stress inductor tunicamycin (TM) significantly decreased the expression of FAM3A at both mRNA and protein levels, which was shown to be dependent on the induction of reactive oxygen species (ROS). Overexpression of FAM3A attenuated TM-induced apoptosis and activation of ER stress factors, but had no effect on ER calcium metabolism in HT22 cells. We also found decreased mitochondrial ROS generation, inhibited cytochrome c release and preserved mitochondrial membrane potential (MMP) in FAM3A overexpressed cells. In addition, the experiments using isolated mitochondria showed that overexpression of FAM3A attenuated mitochondrial swelling and loss of mitochondrial Ca(2+) buffering capacity after TM exposure. By using specific targeted small interfering RNA (siRNA) to knockdown the expression of the C/EBP homologous protein (CHOP), we found that FAM3A-induced protection and inhibition of ER stress was mediated by inverting TM-induced decrease of Wnt through the CHOP pathway. Our study demonstrates a pivotal role of FAM3A in protecting against TM-induced cytotoxicity via regulating CHOP-Wnt pathway, and suggests the therapeutic values of FAM3A overexpression against ER stress-associated neuronal injury.

Clinical characteristics of fetal and neonatal outcomes in twin pregnancy with preeclampsia in a retrospective case-control study: A STROBE-compliant article.

The aim of our study was to compare the clinical characteristics of fetal and neonatal outcomes in twin pregnancies between women with preeclampsia (PE) and those with normotension in a Chinese population.There were 143 preeclamptic women and 367 normotensive women with twin pregnancies included in this retrospective case-control study. The baseline characteristics and perinatal outcomes were collected and compared between the groups. Multiple logistic regression and linear regression were used to assess the correlations between PE and the outcomes.Significant increases were observed in the frequencies of preterm delivery (OR = 2.75, P < 0.001), iatrogenic preterm birth (OR = 3.52, P < 0.001), and IUGR (OR = 2.94, P = 0.001) in the PE group, and the PE group had more than a 2-fold risk of adverse neonatal outcomes. Preeclamptic twin neonates had lower birth weights (ß = -147.34, P = 0.005; ß = -169.47, P = 0.001). The comparison on the discordance of intertwin weight was not significantly different.Twin pregnancies with PE are associated with worse perinatal outcomes. The adverse outcomes of preeclamptic twin pregnancies may be associated with lower birth weights rather than the discordance of the intertwin weight, which requires further confirmation. The results may provide helpful references for better clinical assessments, evaluations of prognosis, and a deeper understanding of preeclamptic twin pregnancies.

[Study on the relationship between human leucocyte antigen and parents' antigen sharing rate and the incidence of pregnancy induced hypertension].

OBJECTIVE: To study the relationship between human leucocyte antigen (HLA), parents' sharing rate and the incidence of pregnancy induced hypertension (PIH), and investigate its immunopathogenetic roles to severe PIH. METHODS: Newborn's and their parents' peripheral blood DNA was extracted and HLA phenotypes were studied by sequence-specific primers polymerase chain reaction (SSP-PCR) in 57 with PIH and 46 normal pregnancy. RESULTS: The frequency of DRB1 * 0306, DRB1 * 0405, DRB1 * 0315, DRB1 * 0403, DRB1 * 1304, QB1 * 03032/33, DQB1 * 0502 in women with PIH was increased significantly and the frequency of DRB1 * 0407, DRB1 * 0317, DQB1 * 05031 were lower than controls. And the risk to PIH of women with DRB1 * 0306, DRB1 * 0405, DQB1 * 0502 were higher than others (RR: 9.76, 6.34, 4.20), and its gene-frequency was higher than controls (P < 0.01). Frequency of DQB1 * 0502, DRB1 * 0405 in PIH's newborns were higher than controls (P < 0.05), but DRB1 * 1304, DQB1 * 05031 were lower than controls, with significant difference (P < 0.05); The gene-frequency of fathers of the two groups weren't different. The HLA sharing rate of mothers or fathers of the two groups weren't different. But that of mother-fetus was higher in PIH than controls. Two locus alleles of PIH group constructed haplotype, and the DRB1 * 0315-DQB1 * 0502, DRB1 * 0405-DQB1 * 06012 antibody was positive with hypertension and protenuria (P < 0.05). CONCLUSION: PIH is associated with HLA, and the over expression of HLA genes was a severe cause of PIH.

MicroRNA-155 inhibits migration of trophoblast cells and contributes to the pathogenesis of severe preeclampsia by regulating endothelial nitric oxide synthase.

The aim of the present study was to characterize the role of microRNA (miR)-155 in the pathogenesis of severe preeclampsia (PE). A total of 19 severe preeclampsic and 22 normal placentas were collected to measure miR-155 and endothelial nitric oxide synthase (eNOS) expression using quantitative (q)PCR and western blot analysis. The results demonstrated a significant increase in the levels of miR-155 and decreased eNOS expression in the severe preeclampsic placentas, as compared with the normal controls. In order to examine the function of miR-155 in the human placenta, the HTR8/Svneo cell line was transiently transfected with an miR-155 mimic or its inhibitor, anti-miR-155. It was confirmed that miR-155 may suppress the expression of eNOS in HTR-8/SVneo cells. Furthermore, a transwell insert invasion assay demonstrated that miR-155 inhibited cell invasion in trophoblast cells, and the effect was rescued by over expression of eNOS. The present study revealed that miR-155 has a negative regulatory role in the migratory behavior of HTR-8/SVneo cells via modulating eNOS.