OBJECTIVETo investigate the role of nuclear factor-κB (NF-κB) activation in bilirubin-induced apoptosis of rat hippocampal neurons and the effect of TAT-NBD intervention on bilirubin neurotoxicity.

METHODSPrimary-cultured rat hippocampal neurons were treated with TAT-NBD in the initial 6 or 24 h or in the latter 6 h during a 24-h bilirubin exposure of the cells (early, continuous and late intervention groups, respectively). Immunocytochemistry was performed to detect NF-κB p65 protein expression, and the cell survival and apoptosis were assessed with a modified MTT assay, Annexin V-FITC/PI and TUNEL assay. IL-1β concentration in the supernatant was determined with ELISA.

RESULTSCompared with the control cells, bilirubin-treated cells showed a significantly increased NF-κB p65 protein expression (P<0.01), which reached the peak level at 6 and 24 h (P<0.01). The cell survival rate in early TAT-NBD intervention group was (80.784∓9.767)%, significantly lower than that of the control group (P<0.01) but higher than that of bilirubin group (P<0.01); the apoptotic rate in early TAT-NBD intervention group was significantly higher than that of control group (P<0.01) but lower than that of bilirubin group (P<0.01). IL-1β concentration was significantly lower in early TAT-NBD intervention group (15.348∓0.812 pg/ml) than in bilirubin group (P<0.05). The continuous and late TAT-NBD intervention groups showed comparable cell survival rate, apoptotic rate and IL-1β concentration with bilirubin group (P>0.05).

CONCLUSIONNF-κB bidirectionally regulates bilirubin-induced apoptosis of rat hippocampal neurons. Selective inhibition of the early peak of NF-κB by TAT-NBD offers neuroprotective effect. TAT-NBD can be potentially used for prophylaxis of bilirubin-induced brain injury.

Animals ; Apoptosis ; drug effects ; Bilirubin ; toxicity ; Cell Survival ; Cells, Cultured ; Female ; Hippocampus ; cytology ; Interleukin-1beta ; metabolism ; Male ; Neurons ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism

Objective To explore the relationship of four kinds of lifestyle factors,namely,prenatal passive smoking,hair dyeing or perming,exposure to noise,living in a house renovated in the past one year,with congenital heart disease.Methods A hospital-based case-control study was conducted.Totally 270 mothers in the case group and 1633 mothers in the control group were interviewed through a face-to-face questionnaire survey.A generalized linear model was employed to investigate the association between congenital heart disease and prenatal lifestyle factors.Results Both in Model 1 and Model 2,prenatal hair dyeing or perming had no association with congenital heart disease.On the other hand,prenatal passive smoking,exposure to noise and living in a house renovated in the past one year all increased the risk of congenital heart disease.After adjustment for all confounders,the OR values were 1.771 (95％ CI:1.079-2.909),2.079 (95％ CI:1.310-3.298),and 2.494 (95％ CI:1.511-4.116),respectively.Conclusion Prenatal passive smoking,exposure to noise and living in a house renovated in the past one year are the risk factors for congenital heart disease.It is very important to avoid such factors during pre-pregnancy and pregnancy.

Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a traditional Chinese herbal medicine. Some recent studies prove its distinguished neuroprotective effect. These neuroprotective mechanisms have become hot points and show closely correlated to activating adenosine A1 receptor, ameliorating the function of cholinergic nerve, regulating ion channel homeostasis, retarding oxidative stress and apoptosis of the neurocytes, promoting nerve growth, having an influence on astrocytes and being ableto penetrate though blood brain barrier. In this review, we present the neuroprotective mechanisms of paeoniflorin in the following eight aspects.
Animals ; Apoptosis ; drug effects ; Benzoates ; analysis ; pharmacology ; Bridged-Ring Compounds ; analysis ; pharmacology ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Glucosides ; analysis ; pharmacology ; Humans ; Monoterpenes ; Neurons ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; analysis ; pharmacology ; Oxidative Stress ; drug effects ; Paeonia ; chemistry

Objective To investigate the effect of folic acid supplementation in childbearing aged women during pregnancy on the birth weight of newborns in Shaanxi province.Methods A questionnaire survey was conducted among the childbearing aged women selected through multistage stratified random sampling in Shaanxi during 2010-2013,all of these childbearing aged women were in pregnancy or had definite pregnancy outcomes.The birth weight of newborns and folic acid supplementation during pregnancy were used as the dependent variables and independent variables respectively in multiple linear regression model and quantile regression model and confounding factors were controlled.Results Multiple linear regression analysis showed that the birth weight of newborns whose mothers had folic acid supplementation during pregnancy were significantly higher than those whose mothers had no folic acid supplementation during pregnancy,an average increase of 29.56 g (B=29.56,t=4.69 and P＜0.01).Quantile regression analysis showed from very low to higher percentiles (q=0-0.55,q=0.65,q=0.75-0.80),the birth weights of newborns whose mothers supplemented folic acid were higher than those whose mother did not supplement folic acid,the difference was significant,but the increase varied.As the increase of the percentiles of birth weight,the body weight increase declined gradually in those whose mothers had folic acid supplementation compared with those whose mothers had no folic acid supplementation.Conclusion Folic acid supplementation during pregnancy can increase the birth weight of newborns,the influence was greater in newborns with lower body weight than in newborns with higher body weight.

Objective To explore the association between exposure to ambient air pollution during pregnancy and congenital heart disease so as to provide evidence for primary prevention of congenital heart disease.Methods Epidemiologic studies on ambient air pollution and congenital heart diseases were reviewed.Summary risk estimates were calculated at high versus low exposure levels and risk per-unit-increase in continuous pollutant concentration.Meta-analysis was conducted with Stata 12.0 software.Results A total of 20 articles in English were qualified for inclusion.Results from Meta-analysis showed that CO exposures were related to the increase on the risk of tetralogy of fallot (high versus low exposure level OR=1.22,95％CI:1.03-1.44),while the exposures to NO2 were related to the increase on risk of coarctation of aorta (per 10 mm3/m3 OR=1.01,95％CI:1.01-1.20).Exposures to O3 were related to the increase on risk of atrial septal defect (per 10 mm3/m3 OR=1.14,95％CI:1.03-1.26),and PM10 exposures were related to the increase on risk of atrial septal defect (per 10 μg/m3 OR=1.10,95％CI:1.03-1.19).In addition,there were inverse associations between CO and atrial septal defect and between PM10 and ventricular septal defect.Conclusion Exposures to CO,NO2,O3,PM10 during pregnancy seemed to be associated with congenital heart diseases.

Macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four M2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research.
Humans ; Macrophages/metabolism* ; Phenotype ; Proteomics ; THP-1 Cells

Objective: To investigate the relationship between maternal disease in early pregnancy of women of childbearing age and congenital heart disease of neonates. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. A questionnaire survey was conducted in the childbearing-aged women during 2010-2013 in Shaanxi province. Propensity score (PS) matched (1∶1) analysis was used to match participants with diseases to those without disease in early pregnancy. Through the control of the confounders step by step, a logistic regression model was established to evaluate the ORs of congenital heart disease according to the independent variable of maternal disease. Results: A total of 28 680 pairs of mothers and infants were included in this study, the proportion of the women with disease in early pregnancy was 20.25% (5 807). After PS matching, 5 436 pairs were matched. After adjusting all confounding factors, the multivariable logistic regression analysis results showed that maternal disease (OR=1.86, 95%CI: 1.23-2.81), especially cold (OR=2.19, 95%CI: 1.46-3.28), gynecological disease (OR=4.74, 95%CI: 2.03-11.09) and diabetes (OR=14.00, 95%CI: 1.64-119.21), in early pregnancy were the risk factors for congenital heart disease of neonate. Conclusion In women of childbearing age, disease in early pregnancy, especially cold, gynecological disease and diabetes, can increase the risk of congenital heart disease in neonates.

Objective: To investigate the interaction of pregnancy-induced hypertension and history of preterm birth on the risk of small for gestational age. Methods: Stratified multistage random sampling method was used to choose samples from 30 districts and counties of Shaanxi province. Information on childbearing-age women with their children between January 2010 and November 2013 was retrospectively collected through face-to-face questionnaire survey. The childbearing-aged women were in pregnancy or having had definite outcomes of pregnancy. Enumeration data were described by percentage, and measurement data were described by Mean±SD, and χ² test was used to compare the rates. Unconditional logistic regression analysis was performed to estimate the interaction between pregnancy-induced hypertension and history of preterm birth on the risk of small for gestational age, and by using small for gestational age as dependent variables, pregnancy-induced hypertension and history of preterm birth as independent variables. Confounding factors were under control. Firstly, the association between pregnancy-induced hypertension and small for gestational age has been analyzed in primiparas, secondly, interaction of pregnancy-induced hypertension and history of preterm birth on the risk of small for gestational age has been analyzed in multiparas. Results: A total of 25 751 women of childbearing age and their children were recruited. 60.55% (15 592/25 751) were primiparas, 39.45% (10 159/25 751) were multiparas, the rate of history of preterm birth was 1.89% (192/10 159) for multiparas. The incidence rates of pregnancy-induced hypertension and small for gestational age were 1.55% and 15.49% in pregnant woman (400/25 751) and their newborns (3 990/25 751). Unconditioned logistic regression analysis showed that compared with woman without pregnancy-induced hypertension, primiparas with pregnancy-induced hypertension had increased risk of small for gestational age (OR=1.43, 95%CI: 1.02-2.00, P=0.041). Regarding multiparas, the main effect of pregnancy-induced hypertension had a positive correlation with small for gestational age (OR=1.34, 95%CI: 0.91-1.96), but there was no statistical significance (P=0.138). The main effect of history of preterm birth was positively correlated with small for gestational age (OR=1.61, 95%CI: 1.13-2.31, P=0.009). The interaction term "pregnancy-induced hypertension×history of preterm birth" was positively associated with risk of small for gestational age (OR=5.93, 95%CI: 1.19-29.61, P=0.030). Conclusions Pregnancy-induced hypertension was associated with increased risk for small for gestational age in both primiparas and multiparas, and history of preterm birth further increased risk for small for gestational age in pregnant women with pregnancy-induced hypertension, indicating that there was multiplication interaction between pregnancy-induced hypertension and history of preterm birth.