Maternal serum Netrin-1 levels as a new biomarker of preeclampsia

Aim: The aim of this study was to investigate whether the Netrin-1 levels in maternal serum was associated with the presence of preeclampsia (PE).

Methods: Total 72 patients, including 28 normal pregnant women and 44 patients with PE, were included in this study. Maternal serum Netrin-1 concentration was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Maternal serum Netrin-1 levels were detected statistically higher in preeclamptic group than control group (p?p?>?0.05).

Conclusion: Maternal serum Netrin-1 has a potential to be a new marker for the detection of PE.     

Maternal serum sestrin 2 levels in preeclampsia and their relationship with the severity of the disease

Objective: To investigate sestrin 2 (SESN2) levels in preeclampsia (PE) cases and uncomplicated pregnancies.

Methods: Cross-sectional study including 26 pregnant women with PE, 24 with severe-PE, and 30 randomly selected healthy pregnant women.

Results: The mean arterial pressure, severe proteinuria, number of HELLP syndrome cases, and serum SESN2 levels in the severe PE group were significantly higher than those in the other groups (p < 0.001, p < 0.001, p = 0.006, and p = 0.004, respectively). Negative correlation was found between the birth interval (r = ?.262, p = 0.019) and the SESN2 level.

Conclusion: SESN2 seems to play a role in the pathophysiology of PE, especially in severe PE cases.     

Reduction in serum paraoxonase level in newborns with hyperbilirubinemia as a marker of oxidative stress

Objective: Indirect bilirubin exerts an antioxidant effect when increased mildly. This study aimed to investigate whether increased bilirubin levels lead to an oxidant effect in newborns with hyperbilirubinemia requiring phototherapy.

Patients and methods: The study included 30 term newborn infants aged 0–7 days with indirect hyperbilirubinemia requiring phototherapy and no comorbid disease as the study group. In addition, 30 term healthy newborn infants aged 0–7 days without indirect hyperbilirubinemia were employed as a control group. Serum triglyceride, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), serum paraoxonase (PON) levels and malondialdehyde (MDA) levels were compared between the groups.

Results: Serum MDA, total bilirubin, and LDL and HDL levels were significantly higher and the serum PON level was significantly lower, in the study group compared with the controls (p Conclusion: In newborns with hyperbilirubinemia requiring phototherapy, an increased bilirubin level causes oxidative stress by decreasing the level of serum PON and increasing the level of MDA.     

过表达SATB1保护人滋养细胞氧化应激损伤的机制研究

目的 探讨富集AT序列的特异性结合蛋白1（SATB1）参与人绒毛外滋养细胞株（HTR8/SVneo）氧化应激损伤的机制。方法 收集2013年9月至2014年9月在重庆医科大学附属第一医院产科行选择性剖宫产术的子痫前期孕妇（n=22）和正常足月妊娠行择期剖宫产术的孕妇的胎盘组织（n=22）。采用免疫组化和Western blotting（WB）检测正常晚孕期及子痫前期胎盘组织中SATB1的表达。构建SATB1过表达慢病毒载体（LV-SATB1）和阴性对照载体（LV-NC）。将滋养细胞分为正常培养对照组、缺氧/复氧（H/R）培养组、LV-SATB1+H/R培养组、LV-NC+H/R培养组。利用免疫荧光和WB法检测SATB1在各组细胞中的表达。采用流式细胞仪检测细胞凋亡指数及细胞内活性氧（reactive oxygen species, ROS）水平。利用Transwell小室模型检测细胞的体外侵袭率。结果 SATB1在子痫前期中的表达显著低于正常晚孕组（0.24±0.02 vs. 0.12±0.01, t=9.35,P<0.05）。转染LV-SATB1可显著提升H/R培养组的SATB1蛋白水平（0.92±0.17 vs. 0.58±0.15,P<0.01）。LV-SATB1可抑制H/R导致的细胞凋亡率上升及ROS聚集（P<0.01）。H/R组细胞侵袭能力低于正常培养组;上调SATB1的表达可提升H/R组细胞的体外侵袭能力（34.33±10.08 vs. 19.33±6.52,P<0.05）。结论    过表达SATB1可以逆转滋养细胞氧化应激损伤,其有望成为研究子痫前期发病机制的新靶点。     

Serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1) level,and neonatal outcome in early onset,late onset preeclampsia,and normal pregnancy

ABSTRACT

Objective: To compare the level of serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1), and neonatal outcome in early onset preeclampsia (EO-PE), late onset preeclampsia (LO-PE), and normal pregnancy (NP).

Methods: In this prospective observational case control study, HO-1 and sFlt-1 levels were measured in blood samples within 24 h of hospital admission. Preeclampsia cases were divided into two groups based on gestational age at delivery: EO-PE (<34 weeks) and LO-PE (≥34 weeks). A total of 45 patients were involved in this study.

Result: Maternal serum level of sFlt-1 was higher in EO-PE than LO-PE and NP groups (mean ± SD; 14.50 ± 17.12 ng/ml vs 5.20 ± 6.69 ng/ml vs 2.72 ± 1.2 ng/ml [p = 0.020]. Maternal serum level of HO-1 was not different between EO-PE, LO-PE, and NP groups (p = 0.681). Birthweights were significantly lower in the EO-PE group compared with the LO-PE and NP groups (1580 ± 536 g vs 2635 ± 578 g vs 3010 ± 371 g [p = 0.000]). The rate of small for gestational age infant (26.7% vs 6.7% vs 0%; p = 0.046) and perinatal death (20% vs 0 vs 0; p = 0.037) was also significantly higher in EO-PE compared to LO-PE and NP. The maternal sFlt-1 level was negatively correlated with birthweight (p = 0.006; CC = ?0.445).

Conclusion: This study did not find a correlation between maternal HO-1 levels and sFlt-1 levels. Maternal serum sFLt-1 levels in preeclampsia were higher in EO-PE and were associated with a worse perinatal outcome.     

Study of serum levels of superoxide dismutase in preeclampsia and eclampsia: role of the test as a predictive tool

AIM: To report serum levels of superoxide dismutase in women with preeclampsia and eclampsia. To document the use of the value as a predictive tool for deciding the time of onset of subsequent convulsions with fulminating eclampsia and use of the value as a marker for obstetric intervention in clinical severe preeclampsia and eclampsia. METHODS: Superoxide dismutase concentration was measured in a consecutive study in sera of women admitted in obstetric ward for preeclampsia and eclampsia, and compared with sera of normotensive, healthy pregnant women in third trimester. Three mL venous blood was subjected to superoxide dismutase estimation by pyrogallol autoxidation method. RESULTS: We found statistically significant difference (P < 0.05) in mean superoxide dismutase levels of normotensive pregnant women; and preeclamptic and eclamptic subjects, no statistically significant difference was found in between value of enzyme in preeclampsia and eclampsia (P > 0.05). Superoxide dismutase levels in two pregnancy outcomes; live births and still births, shows significant difference (P < 0.05), being 1.03 U/mL and 0.52 U/mL, respectively. The comparison of values before delivery and after delivery showed highly statistically significant difference (P < 0.001) in both groups separately. The cut-off value of serum superoxide dismutase 0.52 U/mL has sensitivity 68.5%, specificity 59.5% and negative predictive value of 78.6%, for predicting the fetal death as outcome of pregnancy with severe grade of disease. CONCLUSION: We found low levels of serum superoxide dismutase, less than 0.52 U/mL, being the predecessor of fulminating eclampsia. Our results support this predictive value of serum superoxide dismutase level as important in deciding the time of intervention as termination of pregnancy.     

子痫前期中的氧化应激和抗氧化治疗

伴随着子痫前期（PE）过度的氧化应激状态,胎盘和母体的循环系统也发生一系列的抗氧化反应,这些改变的抗氧化反应能导致脂质过氧化物增加,也能影响细胞信号转导和某些与血管活性物质合成有关的酶通路。基于上述发病机制,推测妊娠期补充抗氧化剂可能对抗氧化应激进而预防或延迟PE的发生。许多学者试验性地采用抗氧化治疗如补充维生素C、维生素E、硒元素等来预防PE的发生,但结果并不乐观,尚需大量前瞻性研究予以充实和完善。     

SDF-1/CXCL12 and CXCR4 gene variants,and elevated serum SDF-1 levels are associated with preeclampsia

Objective: We aimed to compare the frequencies of stromal cell-derived factor-1 (SDF-1) 3′A and CXCR4 single-nucleotide polymorphisms (SNPs) and serum SDF-1 levels in patients with preeclampsia (PE).

Methods: In total, 89 women with PE and 89 control women were included in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. Enzyme-linked immunosorbent assay method was used to measure serum SDF-1 level.

Results: For SDF-1 3′A SNP, the frequency of GA genotype, total number of GA and AA genotypes, and the A allele frequency was higher in PE patients than controls (p = 0.04, 0.023, and 0.029, respectively). For CXCR4 SNP, the frequency of CT genotype, total number of CT and TT genotypes, and the T allele frequency were higher in PE patients than controls (p = 0.04, 0.006, and 0.005, respectively). SDF-1 serum level was detected higher in preeclamptic women compared with controls (p = 0.001). In PE patients, there was no significant association between serum SDF-1 levels and genotypes of SDF-1 3′A SNP. SDF-1 level was significantly higher in patients bearing CXCR4 CT genotype than CC genotype (p = 0.001). Furthermore, SDF-1 levels in patients bearing CT+TT genotype were found higher than that of patients with CC genotypes (p = 0.001).

Conclusion: Results of our study suggest that SDF-1 3′A and CXCR4 polymorphisms and elevated serum SDF-1 levels may have a role in the development of PE.     

Ischemia-modified albumin as an oxidative stress marker in preeclampsia

Objective.?We examined serum ischaemia-modified albumin (IMA) levels in normal pregnant and preeclamptic women. The primary aim of our study was to assess IMA in women with mild and severe preeclampsia.

Methods.?Serum ischaemia-modified albumin levels were measured in 18 normotensive and 36 preeclamptic pregnant women by enzyme linked immuno-sorbent assay. Patients were subdivided as having either mild (n?=?18) or severe preeclampsia (n?=?18). Receiver operating characteristic curve was constructed, and sensitivity and specificity were calculated based on the best cut-off.

Results.?IMA levels were significantly higher in the mild and severe preeclamptic groups than in the control group. IMA with a cut-off point of 0.31 identified women with preeclampsia with sensitivity 80% and specificity 77.8%.

Conclusion.?Our study demonstrates that serum levels of IMA correlate with severity of preeclampsia.     

Maternal cytoglobin (CYGB) serum levels in normal and preeclamptic pregnancies

Objective: To investigate cytoglobin levels in women with preeclampsia and women with uncomplicated pregnancies.

Materials and methods: A cross-sectional study including 26 pregnant women complicated with early-onset preeclampsia (EO-PE) and 26 pregnant women complicated with late-onset preeclampsia (LO-PE) were recruited for the study group. Twenty-seven healthy pregnant women selected randomly were included in the control group. The serum CYGB concentrations were measured using an enzyme-linked immunosorbent assay.

Results: Gestational age at delivery and mean birth weight were significantly lower in the preeclampsia groups than in the control group and were found to be the lowest in the EO-PE group (p?p?p?=?1.000).

Conclusions: Serum CYGB levels were significantly higher in patients with EO-PE and LO-PE as compared to healthy pregnant women.     

Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis

Background/aims: A meta-analysis of maternal serum ischemia-modified albumin (IMA) and fetal cord-blood IMA concentrations in normal pregnancy (NP) compared to non-pregnant healthy controls (HC) and in preeclampsia (PE) compared with normal pregnant controls were studied.

Methods: All major databases were searched for eligible studies. We included eight studies comparing serum IMA between NP and HC, 14 studies comparing serum IMA between PE and NP and five studies comparing cord-blood IMA between PE and NP groups. Meta-analyses on these included studies were performed using Review Manager 5.3. Pooled-overall effect size as standardized mean difference (SMD), publication bias, subgroup, and sensitivity analysis data were generated.

Results: Random-effects meta-analysis indicated a significant increase in serum IMA in the NP group (SMD?=?0.98, p?=?.01) and the PE group (SMD?=?0.94, p?p?Conclusions: This meta-analysis, the first of its kind showed that the increased serum IMA concentrations were indicative of increased oxidative stress in NP and PE. Measurement of maternal serum IMA and fetal cord-blood IMA concentrations were useful as simple, novel, and inexpensive markers of oxidative stress (OS) status in PE patients. Future large-scale studies are needed to explore IMA in relationship to the disease severity in PE.     

ABCA1基因R219K与血脂及子痫前期易感性的相关性研究

目的探讨福建省汉族人群三磷腺苷结合转运子A1基因（ABCA1）R219K单核苷酸多态性（SNP）和子痫前期（preeclampsia）及其血脂水平的关联性。方法研究对象621例,包括对照组316例,子痫前期病例组305例。采用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）法鉴定ABCA1基因外显子区R219K单核苷酸多态性并测定血脂水平。结果 ABCA1基因R219K位点K等位基因频率和RK＋KK基因型频率在子痫前期病例组明显降低,差异有高度统计学意义P〈0.001）。子痫前期病例组内RK＋KK基因型患者血清甘油三酯（TG）浓度低于RR基因型,而HDL-C浓度刚好相反,差异有高度统计学意义（P〈0.001）。结论福建省汉族人群ABCA1基因R219K中,K等位基因可能是子痫前期的独立的保护因子,其机制可能是通过提高血液中HDL-C水平,降低TG水平,从而降低了子痫前期合并血脂代谢紊乱的风险性。     

Increased breath markers of oxidative stress in normal pregnancy and in preeclampsia

OBJECTIVES: The purpose of this study was to compare the intensity of oxidative stress in normal pregnancy, preeclampsia, and nonpregnant women using a breath test. STUDY DESIGN: We studied primiparous women in third trimester pregnancy (38 uncomplicated, 26 with preeclampsia) and 60 nonpregnant control subjects. Volatile organic compounds (VOCs) in alveolar breath were analyzed by gas chromatography/mass spectroscopy to construct the breath methylated alkane contour (BMAC), a 3-dimensional display of abundance of C4-C20 alkanes and monomethylated alkanes. RESULTS: The mean volume under curve (VUC) of the BMAC was significantly higher in preeclampsia patients than in normal pregnant women (P < .003) and nonpregnant control subjects (P < .005). A predictive model employing 5 VOCs distinguished preeclampsia from uncomplicated pregnancy (sensitivity = 92.3%, specificity = 89.7%; cross-validated sensitivity = 88.5%, specificity = 79.3%). CONCLUSION: A breath test significantly demonstrated greater oxidative stress in women with preeclampsia than in uncomplicated pregnancy and nonpregnant control subjects. The breath test accurately identified women with established preeclampsia, but further studies are required to determine if this test can predict the onset of disease.     

血管内皮细胞氧化应激反应对细胞粘附分子表达的影响

目的　通过对过氧亚硝酸阴离子所诱导的血管内皮细胞的氧化应激反应对内皮细胞表面粘附分子的影响的研究 ,探讨妊娠高血压疾病的发病机制。方法　应用人类脐静脉血管内皮细胞 (humanumbilicalveinendothelialcell,HUVEC)作为体外细胞模型。SIN - 1(3-Morpholinosydnonimine -HCL)作为细胞培养液中过氧亚硝酸阴离子发生器 ,用以刺激培养的血管内皮细胞。以ELISA法检测血管内皮细胞表面粘附分子 ,包括细胞间粘附分子 (intercelluaradhesionmolecule ,ICAM)、血管细胞粘附分子 (vascularadhesionmolecule,VCAM)、P -选择素 (P -Selectin)及E -选择素 (E -Selectin)的表达水平。结果　SIN - 1处理培养之血管内皮细胞 0 5h、 1h ,2h及 4h ,细胞表面粘附分子在经SIN - 1处理 4h后表达水平显著增加 ,呈时间依从性递增的趋势 ;SIN - 1处理培养HUVEC 4h后 ,血管细胞粘附分子 (VCAM)、P -选择素及E -选择素的表达水平较未经SIN - 1处理的HUVEC显著增加 :VCAM (0 115± 0 0 2 2 )vs (0 0 35± 0 0 11) (P <0 0 5 ) ;P -选择素 (0 0 80± 0 0 10 )vs (0 0 34±0 0 0 1) (P <0 0 5 ) ;E -选择素 (0 12 9± 0 0 36 )vs (0 0 37± 0 0 0 4 ) (P <0 0 5 )而ICAM的表达没有显著的变化 (0 2 92± 0 0 1)     

Role of serum levels of irisin and oxidative stress markers in pregnant women with and without gestational diabetes

Irisin regulates glucose levels, lipid levels, insulin sensitivity, and low-grade inflammation. Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy, and is associated with increased rates of perinatal problems. Oxidative stress biomarkers have a role in the pathogenesis of patients with GDM. In total, 94 patients were included in our study including 46 control patients and 48 patients with GDM. Fasting blood glucose, HOMA-IR, total oxidative stress (TOS), irisin, and oxidative stress index (OSI) levels of the patients were measured. Serum OGTT, OSI, irisin HOMA, TOS, and insulin levels were statistically significantly higher in the patient group than in the control group. This was the first study to investigate the relation between serum irisin levels and oxidative stress markers in patients with GDM. The results revealed that irisin is an oxidative stress marker and a metabolic protective hormone.