Mirror syndrome after fetoscopic laser therapy for twin-twin transfusion syndrome due to transient donor hydrops that resolved before delivery. A case report.

BACKGROUND: Mirror syndrome is a rare complication of twin-twin transfusion syndrome (TTTS). Its clinical picture includes massive edema, oliguria, and hemodilution in the context of fetal hydrops. The occurrence of mirror syndrome after fetoscopic laser therapy for TTTS has been well documented, but resolution of mirror syndrome before delivery has not been reported in the literature. CASE: A 33-year-old woman was referred to our institution at 23(6)/7 weeks' gestation for TTTS, which had been treated with amnioreduction twice: at 21 and 22 gestational weeks, respectively. Mirror syndrome was diagnosed after fetoscopic laser therapy for TTTS at 24 weeks' gestation due to maternal manifestations of pulmonary edema, skin edema, anemia, low blood protein concentration and proteinuria accompanied by donor hydrops. The maternal respiratory symptoms then gradually abated in <2 weeks along with improved fetal condition, resulting in a delivery with favorable outcomes at 36 weeks' gestation. CONCLUSION: Manifestation of mirror syndrome after fetoscopic laser therapy in twin-twin transfusion due to donor hydrops doesn't necessarily predict a poor perinatal outcome.

Increased autophagy in the placental territory of selective intrauterine growth-restricted monochorionic twins.

SUBJECT: This study investigates the placental autophagic activity in growth-restricted fetuses in the monochorionic (MC) twin model. PATIENTS AND METHODS: Forty MC twins were prospectively enrolled in this study, including 21 with and 19 without selective intrauterine growth restriction (sIUGR), defined as birth weight below the tenth percentile. The sIUGR group was subdivided on the basis of present versus absent or reversed umbilical artery end-diastolic flow at Doppler. Placenta samples were taken after delivery from each twin placenta territories. After protein extraction, Western blot was used to determine light chain 3 (LC3)-II placental protein expression in sIUGR and appropriately grown (appropriate-for-gestational age, AGA) twins. RESULTS: The LC3-II was significantly higher in the sIUGR twin placental territory than in their AGA counterparts. In the sIUGR group, LC3-II fold change was significantly increased compared with that in the AGA cotwins (2.28 vs 1.04, p < 0.05). Placental LC3-II protein expression was particularly stimulated in the MC sIUGR group with abnormal umbilical artery Doppler flow compared with AGA controls (p < 0.05, one-way analysis of variance test). CONCLUSIONS: In MC twins, the placental autophagic activity is different between sIUGR and AGA cotwins. The placenta territory with the least blood flow perfusion has the highest autophagic activity.

The neurological outcomes of surviving twins in severe twin-twin transfusion syndrome treated by fetoscopic laser photocoagulation at a newly established center.

OBJECTIVE: To evaluate the incidence and predictive factors of poor neurological outcome in survivors of twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP). METHODS: Brain magnetic resonance imaging (MRI) and neurodevelopmental assessment were performed at a corrected age of 1 year in survivors of TTTS treated by FLP. Severe neurological abnormality was defined as either the presence of severe clinical neurodevelopmental disability or severe anomalies, visualized on MRI of the brain. RESULT: In a consecutive series of 46 cases treated by FLP, the total survival rate was 66.3%; survival of at least one was 80.4%. Severe neurodevelopment disability was 6.7 % (4/59) and the presence of a severe anomaly on brain imaging was 8.8% (5/57), which combined to a clinical or MRI abnormality rate of 10.5% (6/57). Univariate analysis revealed that early gestational age at delivery was the most significant predictor. However, the multiple logistic regression model did not identify any significant variables. CONCLUSION: In this small series, we determined a rate of clinical neurologic impairment rate at the age of 1 year of 6.7%, which compares to what has been published.

Placenta share discordance and umbilical artery Doppler change after antenatal betamethasone administration in monochorionic twins with selective intrauterine growth restriction: is there a link?

This study was designed to evaluate the degree of placenta share discordance in relation to the betamethasone-induced return of positive end-diastolic flow in monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was defined as one twin having an estimated fetal weight below the 10th percentile combined with an estimated fetal weight discordance >25%. The umbilical artery Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the first dose of betamethasone administration was recorded. The estimated individual placental weight in monochorionic twins was obtained by cutting the placenta along the vascular equator into two territories; the placenta share discordance was calculated as [(estimated individual placental weight of appropriated for gestational age twin- estimated individual placental weight of growth restricted twin)/estimated individual placental weight of appropriated for gestational age twin] × 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced return of positive umbilical artery end-diastolic flow. The difference of placenta share discordance and birth weight discordance were not significantly different between twins with and without betamethasone-induced return of positive umbilical artery end-diastolic flow. Thus, according to our study results, it was proposed that although the placenta share discordance correlated with the abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the betamethasone-induced return of positive umbilical artery end-diastolic flow, however, did not reveal the similar relationship with the severity of placenta share discordance.

Early anti-angiogenic proteins expression in amniotic fluid of twin fetuses.

Multiple pregnancies are thought to be associated with a high incidence of perinatal complications such as preterm labor, preeclampsia and low birth weight. But the true mechanisms of these obstetric complications are still uncertain. The components of amniotic fluid reflect the pathophysiology features of the fetus. Amniotic fluid soluble fms-like tyrosine kinase 1(sFLT1), soluble endoglin (sENG), and adiponectin reflect the oxidative stress and pro-inflammatory status and are associated with preeclampsia and fetal growth restriction. We prospectively collected amniotic fluids during amniocentesis from singleton and twin pregnancies. Samples were analyzed for levels of sFLT1, sENG, and adiponectin by enzyme-linked immunosorbent assay. The levels of sENG and sFLT1 were significantly increased in twin pregnancies. Adiponectin was not significantly different between the two groups. These findings would suggest that twin fetuses suffer from more oxidative stress and pro-inflammatory status from the early trimesters.

The relationships of umbilical venous volume flow, birthweight and placental share in monochorionic twin pregnancies with and without selective intrauterine growth restriction.

This study was conducted to investigate the relationship among umbilical venous volume flow, birthweight and placental share in monochorionic twins with or without selective growth restriction. Having excluded cases complicated with twin-to-twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a total of 51 monochorionic twin pregnancies were divided into two groups as with (group 1) and without (group 2) selective intrauterine growth restriction. Umbilical venous volume flow was calculated by multiplying the umbilical vein cross-sectional area by half of the maximal velocity around mid-trimester. The placentas were cut along the vascular equator into two individual placental masses. The discordance of birthweight was calculated as [(birthweight of larger twin-birthweight of smaller twin)/birthweight of larger twin 100%]. The discordances of umbilical venous volume flow and placental share were calculated in a similar fashion. The median umbilical venous volume flow discordances (68.4% and 15.3% in groups 1 and 2 monochorionic twins, respectively) were similar and correlated well with the placental share discordances (66.6% and 18.5% in groups 1 and 2 monochorionic twins, respectively) but not with the birthweight discordance (28.6% and 6.4% in groups 1 and 2 monochorionic twins, respectively) in both groups. We concluded that the umbilical venous volume flow discordance reflects the placental share discordance rather than the birthweight discordance in monochorionic twin pregnancies.

Fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective growth restriction and abnormal umbilical artery Doppler.

AIM: To evaluate fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective intrauterine growth restriction (sIUGR) and absence of end-diastolic velocity in umbilical artery (UA) Doppler. MATERIAL AND METHODS: sIUGR was defined as fetal weight below the 10th percentile in one twin and inter-twin birth weight discordance >25%. The results of Doppler examinations including UA, middle cerebral artery (MCA) and ductus venosus directly prior to (D0), at 24 h (D1) and 48 h (D2) after administration of the first dose of betamethasone were recorded. Cerebral-placenta ratio was defined as MCA pulsatility index (PI) divided by UA-PI. RESULTS: In four (20%) of the 20 cases, the UA Doppler of the growth-restricted twin returned to positive end-diastolic velocity after betamethasone administration. The UA-PI and MCA-PI of the sIUGR twin changed significantly after betamethasone administration: UA-PI was decreased at D1, the MCA-PI was reduced at both D1 and D2, and the cerebral-placenta ratio was not altered after betamethasone administration in the sIUGR twin. CONCLUSION: The hemodynamic changes after betamethasone administration were different between the two monochorionic twin fetuses where one presented with sIUGR and absence of UA end-diastolic velocity. The etiology of a low rate of return of end-diastolic velocity in the sIUGR twin needs further evaluation.

Genome-based expression profiling study of Hunner's ulcer type interstitial cystitis: an array of 40-gene model.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to explore potential molecular mechanisms contributing to the pathogenesis of Hunner's ulcer type interstitial cystitis (IC). METHODS: Dataset acquisitions from Gene Expression Omnibus under platform accession no GSE 11783. We compared global gene expression profiles in bladder epithelial cells from IC patients with Hunner's ulcer corresponding to normal controls. We re-sampling and exploit the correlation structure presented in the dataset through the transcriptional response. For each patient, two bladder biopsies were studied, one from an ulcer area and one from a non-ulcer area. RNA was extracted, and all labeled samples were hybridized to Human Genome U133 Plus 2.0 Array (Affymetrix, CA, USA). RESULTS: The Mahalanobis distance in hierarchical cluster analysis revealed a model of 40 genes expression which is increased in IC and ulcerated IC. Our results can be summarized as follows: First, the expressions of major histocompatibility complex (MHC) class IF and II molecules, leukocyte immunoglobulin-like receptors, hepatitis A virus cellular receptor 2, and interleukin 32 were increased in bladder epithelial from IC and ulcerative IC area. Next, there is an indication of antigen-mediated aggregation of the high-affinity Fc epsilon and gamma RI leading to allergic inflammation through the disease status. Third, the high-affinity Fc gamma RI subunit facilitated T-cell-mediated immune response through the disease status. Such changes, jointly termed "bladder remodeling," can constitute an important long-term consequence of Hunner's ulcer type IC. CONCLUSIONS: Our results indicate that genome-based expression profiling can be used for the diagnostic tests of Hunner's ulcer type IC in clinical practice.

Functional network analysis of the transcriptomes of mesenchymal stem cells derived from amniotic fluid, amniotic membrane, cord blood, and bone marrow.

Using high-density oligonucleotide microarrays and functional network analyses, we examined whether MSCs derived from four different origins exhibited unique gene expression profiles individually and then compared the gene expression profiles of all MSCs with those of fetal organs. Our results indicated that within each group of MSCs from the same origin, the variability of the gene expression levels was smaller than that between groups of different origins. Functional genomic studies revealed the specific roles of MSCs from different origins. Our results suggest that amniotic fluid MSCs may initiate interactions with the uterus by upregulating oxytocin and thrombin receptors. Amniotic membrane MSCs may play a role in maintaining homeostasis of fluid and electrolytes by regulating the networks of endothelin, neprilysin, bradykinin receptors, and atrial natriuretic peptide. Cord blood MSCs may be involved in innate immune systems as the neonatal defense system against the earliest encountered pathogens. Adult bone marrow MSCs may be an important source not only of all blood lineages but also of bone formation. However, in spite of the different gene expression profiles seen in MSCs derived from different origins, a set of core gene expression profiles was preserved in these four kinds of MSCs. The core signature transcriptomes of all MSCs, when contrasted against those of fetal organs, included genes involved in the regulation of extracellular matrix and adhesion, transforming growth factor-beta receptor signaling, and the Wnt signaling pathways. Disclosure of potential conflicts of interest is found at the end of this article.

Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation.

BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. KEY MESSAGE: BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.

Ovarian endometrioma complicated by a Salmonella abscess caused by an enteroovarian fistula: a case report.

BACKGROUND: Salmonella infection occurs primarily in the gastrointestinal tract but may also be found at extraintestinal locations. An ovarian abscess caused by Salmonella is one of the rare extraintestinal infections, and hematogenous spread by bacteremia to a preexisting ovarian cyst has been suggested as the cause of such infections. CASE: A 43-year-old woman presented with diarrhea, fever and an ovarian tumor and was treated initially with antibiotics for Salmonella bacteremia, followed by an exploratory laparotomy due to persistent fever and progressive toxic signs. A pus-containing endometrioma with a thick wall densely adhering to an intestinal segment, with a fistula connecting the 2, was found during surgery. The patient underwent a salpingo-oophorectomy and resection of the intestinal segment, took antibiotics and recovered. Bacterial culture of the abscess showed salmonellosis, and pathology reported a fistula between the ovarian tumor and intestine, suggesting that direct spread through a fistula may be one of the causes of extraintestinal Salmonella infections. CONCLUSION: Salmonella infection located in the ovary is a rare condition, often caused by bacteremia. To the best of our knowledge, this is the first report of an ovarian Salmonella abscess that occurred through a fistula.

The anti-atherosclerotic effect of tanshinone IIA is associated with the inhibition of TNF-α-induced VCAM-1, ICAM-1 and CX3CL1 expression.

Tanshinone IIA is one of the major diterpenes in Salvia miltiorrhiza. The inhibitory effect of Tanshinone IIA on atherosclerosis has been reported, but the underlying mechanism is not fully understood. The present study aimed to study the anti-atherosclerosis effect of Tanshinone IIA on the adhesion of monocytes to vascular endothelial cells and related mechanism. Results showed that Tanshinone IIA, at the concentrations without cytotoxic effect, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated human vascular endothelial cells. The expressions of cell adhesion molecules including VCAM-1, ICAM-1 and E-selectin were induced by TNF-α in HUVECs at both the mRNA and protein levels. The mRNA and protein expressions of VCAM-1 and ICAM-1, but not E-selectin, were both significantly suppressed by Tanshinone IIA in a dose dependent manner. In addition, the TNF-α-induced mRNA expression of fractalkine/CX3CL1 and the level of soluble fractalkine were both reduced by Tanshinone IIA. We also found that Tanshinone IIA significantly inhibited TNF-α-induced nuclear translocation of NF-κB which was resulted from the inhibitory effect of Tanshinone IIA on the TNF-α-activated phosphorylation of IKKα, IKKß, IκB and NF-κB. As one of the major components of Salvia miltiorrhiza, Tanshinone IIA alone exerted more potent effect on inhibiting the adhesion of monocytes to vascular endothelial cells when compared with Salvia miltiorrhiza. All together, these results demonstrate a novel underlying mechanism for the anti-inflammatory effect of Tanshinone IIA by modulating TNF-α-induced expression of VCAM-1, ICAM-1 and fractalkine through inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway in human vascular endothelial cells.

Mitochondrial activation in the growth-restricted fetus of monochorionic twins.

OBJECTIVE: To study the regulatory mechanisms of selective intrauterine growth restriction (sIUGR) independent of confounding genetic factors, monochorionic (MC) twins are the ideal model, because they have identical genomic DNA. We hypothesize that the intrauterine growth restriction fetus has mitochondrial activation compared with its larger counterpart, and sought to demonstrate this using the MC twin model. DESIGN: Fetal cord blood and amniotic fluid of MC twins were prospectively collected during delivery. Mitochondrial DNA of cord blood was measured using real-time quantitative polymerase chain reaction (PCR), and mitochondria in amniotic fluid mesenchymal stem cells (AFMSCs) were analyzed with MitoTracker staining. SETTING: Tertiary referring center. PATIENT(S): Forty-three pairs of MC twins, including 24 pairs with sIUGR and 19 pairs without. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mitochondrial DNA contents were measured and presented as fold difference between the small and large fetuses. After staining with MitoTracker, mitochondrial intensity in AFMSCs was analyzed with the Image J program. RESULT(S): The fold differences of the cord blood mitochondrial DNA content between the small and large twins were significantly higher in the MC twins with sIGUR (2.5 ± 1.2, n = 24 pairs) than in those without sIUGR (1.2 ± 0.3, n = 19 pairs). In addition, mitochondrial staining intensities were significantly higher in the AFMSCs derived from growth-restricted fetuses than from control fetuses. CONCLUSION(S): Mitochondrial activation in the sIUGR fetus of MC twins was likely regulated by locally adverse placental and blood flow conditions, instead of genetic factors.

DNA methylation patterns of imprinting centers for H19, SNRPN, and KCNQ1OT1 in single-cell clones of human amniotic fluid mesenchymal stem cell.

OBJECTIVE: To test the hypothesis that human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature in imprinting centers of H19, SNRPN, and KCNQ1OT1 during in vitro cell culture. MATERIALS AND METHODS: By bisulfite genomic sequencing, we analyzed the imprinting centers of three imprinted genes (including H19, SNRPN, and KCNQ1OT/) in a total of six single-cell clones of human amniotic fluid mesenchymal stem cells at cell passages 7, 8, 9, and 10 during in vitro cell culture. RESULTS: The imprinting centers of H19 and KCNQ1OT1 showed hypermethylation at passage 7 in all single-cell clones of human amniotic fluid mesenchymal stem cells, and there was no significant change in DNA methylation patterns during in vitro cell culture. The imprinting centers of SNRPN showed variable methylation patterns at passage 7 in six single-cell clones, and DNA methylation patterns varied during in vitro cell culture from passages 8 to 10. CONCLUSION: In conclusion, human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature during in vitro cell culture. H19 and KCNQ1OT1 possessed a substantial degree of hypermethylation status, and variable DNA methylation patterns of SNRPN was observed during in vitro cell culture of human amniotic fluid mesenchymal stem cells. Our results urge further understanding of epigenetic status of human amniotic fluid mesenchymal stem cells before it is applied in cell replacement therapy.

Short-term outcomes of fetoscopic laser surgery for severe twin-twin transfusion syndrome from Taiwan single center experience: demonstration of learning curve effect on the fetal outcomes.

OBJECTIVE: To evaluate the learning curve effect on fetal outcomes while using fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) as managed by a newly established single center in Taiwan. MATERIALS AND METHODS: Between October 2005 and October 2010, women diagnosed to have TTTS before 26 weeks of gestation were offered FLP surgery. Cases were divided into first-half and second-half groups to evaluate the learning effect on fetal outcomes including at least one survival rate, two survival rate, and gestational age of delivery. RESULTS: A total of 44 cases with a median gestational age of 20.1 weeks (range 16-25) at operation were included in the study. Overall, both twins survived in 22 (50.0%) cases, whereas only one twin was born alive in 13 (29.5%), and neither was born alive in the remaining nine cases (20.5%). The total survival rate was 64.8%. When comparing the first-half 22 cases and the second-half 22 cases, there were significant improvements in total survival rate (54.7% vs. 75.0%, p = 0.045), a prolonged interval between operation and delivery (62.1 vs. 89.1 days, p = 0.042), and more advanced gestational age of delivery (28.3 vs. 33.0 weeks, p = 0.008) in the second-half 22 cases. CONCLUSIONS: With increasing experience in using fetoscopic guide laser therapy for TTTS, the fetal survival rate could be improved with advanced gestational age at delivery.

MicroRNA and messenger RNA analyses of mesenchymal stem cells derived from teeth and the Wharton jelly of umbilical cord.

Microarray analyses of transcriptomes have been used to characterize mesenchymal stem cells (MSCs) of various origins. MicroRNAs (miRNAs) are short, nonprotein-coding RNAs involved in post-transcriptional gene inhibition in a variety of tissues, including cancer cells and MSCs. This study has integrated the use of miRNA and mRNA expression profiles to analyze human MSCs derived from Wharton's jelly (WJ) of the umbilical cord, milk teeth (MT), and adult wisdom teeth (AT). Because both miRNA and mRNA expression in MT and AT MSCs were so similar, they were combined together as tooth MSCs for comparison with WJ MSCs. Twenty-five genes that were up-regulated in tooth MSCs and 41 genes that were up-regulated in WJ MSCs were identified by cross-correlating miRNA and mRNA profiles. Functional network analysis show that tooth MSCs signature genes, represented by SATB2 and TNFRSF11B, are involved in ossification, bone development, and actin cytoskeleton organization. In addition, 2 upregulated genes of tooth MSCs-NEDD4 and EMP1-have been shown to be involved in neuroectodermal differentiation. The signature genes of WJ MSCs, represented by KAL1 and PAPPA, are involved in tissue development, regulation of cell differentiation, and bone morphogenetic protein signaling pathways. In conclusion, the combined interrogation of miRNA and mRNA expression profiles in this study proved useful in extracting reliable results from a genome-wide comparison of multiple types of MSCs. Subsequent functional network analysis provided further functional insights about these MSCs.

Zinc-chelation contributes to the anti-angiogenic effect of ellagic acid on inhibiting MMP-2 activity, cell migration and tube formation.

BACKGROUND: Ellagic acid (EA), a dietary polyphenolic compound, has been demonstrated to exert anti-angiogenic effect but the detailed mechanism is not yet fully understood. The aim of this study was to investigate whether the zinc chelating activity of EA contributed to its anti-angiogenic effect. METHODS AND PRINCIPAL FINDINGS: The matrix metalloproteinases-2 (MMP-2) activity, a zinc-required reaction, was directly inhibited by EA as examined by gelatin zymography, which was reversed dose-dependently by adding zinc chloride. In addition, EA was demonstrated to inhibit the secretion of MMP-2 from human umbilical vein endothelial cells (HUVECs) as analyzed by Western blot method, which was also reversed by the addition of zinc chloride. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), known to down-regulate the MMP-2 activity, was induced by EA at both the mRNA and protein levels which was correlated well with the inhibition of MMP-2 activity. Interestingly, zinc chloride could also abolish the increase of EA-induced RECK expression. The anti-angiogenic effect of EA was further confirmed to inhibit matrix-induced tube formation of endothelial cells. The migration of endothelial cells as analyzed by transwell filter assay was suppressed markedly by EA dose-dependently as well. Zinc chloride could reverse these two effects of EA also in a dose-dependent manner. Since magnesium chloride or calcium chloride could not reverse the inhibitory effect of EA, zinc was found to be involved in tube formation and migration of vascular endothelial cells. CONCLUSIONS/SIGNIFICANCE: Together these results demonstrated that the zinc chelation of EA is involved in its anti-angiogenic effects by inhibiting MMP-2 activity, tube formation and cell migration of vascular endothelial cells. The role of zinc was confirmed to be important in the process of angiogenesis.

The effects of labor on differential gene expression in parturient women, placentas, and fetuses at term pregnancy.

Labor and its associated pain are thought to have unique impacts on parturient women. The goal of this study was to investigate the effects of labor and associated pain on differential gene expression profiles in the maternal, fetal, and placental compartments. We used microarrays to analyze maternal blood (MB), fetal cord blood (CB), and placental tissue samples in pregnant women after term vaginal deliveries (laboring group) and in term pregnant women after scheduled Ceasarean sections (nonlaboring group). The upregulated genes in the MB of the laboring group are involved in cytokine and nuclear factor-kappa B signaling pathways, regulation of the networks of toll-like receptor 4, and suppressor of cytokine signaling 3. Upregulated genes in the CB of the laboring group are involved in responding to stress and stimuli by regulating the network genes of the T-cell receptor beta locus and the FK506 binding protein 8. Differentially expressed genes in the placenta of the laboring group are involved in nitric oxide transport, gas transport, response to hydrostatic pressure, oxygen transport, acute phase responses, and the tumor necrosis factor-mediated signaling pathway, which are important during the transient hypoxemia and hypoperfusion that occur in the placenta during uterine contractions. Interestingly, few of the genes exhibited simultaneous changes in all three compartments, indicating that different pathways and complex interactions may be involved in human labor. In conclusion, human labor and its associated pain elicit unique gene regulatory changes in MB, placenta, and CB.

Elevated amniotic fluid F2-isoprostane: a potential predictive marker for preeclampsia.

In the complex mechanism of preeclampsia, oxidative stress is an important pathogenic factor, and F2-isoprostane is a marker of oxidative stress and lipid peroxidation. The objective of this study was to identify if the amniotic fluid (AF) levels of F2-isoprostanes were elevated in women who later developed preeclampsia. In this study, we analyzed AF F2-isoprostane concentrations with enzyme immunoassay (EIA), and the EIA results could be validated by quantitative mass spectrometry. The mean AF concentration of F2-isoprostanes was significantly higher in pregnancies with subsequent development of preeclampsia (123.1 ± 57.6 pg/ml, n = 85) than in controls (73.8 ± 36.6 pg/ml, n = 85). The AF elevation of F2-isoprostanes was even higher in the preeclampsia with intrauterine growth restriction group (138.3 ± 65.2 pg/ml, n = 39). The area under the curve of the receiver operating characteristics analysis for AF F2-isoprostanes assay was 0.81, supporting its potential as a biomarker for preeclampsia. These results indicate that oxidative stress existed before the onset of clinical preeclampsia, further suggesting that the elevation of AF F2-isoprostanes may be used as a guide for antioxidant supplementation to reduce the risk and/or severity of preeclampsia.