Cyclin-dependent kinase 5 negatively regulates antiviral immune response by disrupting myeloid differentiation primary response protein 88 self-association.

As a member of the pattern recognition receptors (PRRs) involving in the innate immune system, Toll-like receptors (TLRs) can sense a wide range of microbial pathogens and combat infections by producing antimicrobial products, inflammatory cytokines, and chemokines. All TLRs, with the exception of TLR3, activate a signalling cascade via the myeloid differentiation primary response gene 88 (MyD88). Therefore, the activation of MyD88-dependent signalling pathway must be finely controlled. Herein, we identified that cyclin-dependent kinase 5 (CDK5) negatively regulated TLR-MyD88 signalling pathway by targeting MyD88. Overexpression of CDK5 reduced the production of interferons (IFNs), while a deficiency in CDK5 increased the expression of IFNs in response to vesicular stomatitis virus (VSV) infection. Mechanistically, CDK5 suppressed the formation of MyD88 homodimers, resulting in the attenuated production of IFNs induced by VSV infection. Surprisingly, its kinase activity does not play a role in this process. Therefore, CDK5 can act as an internal regulator to prevent excessive production of IFNs by restricting TLR-MyD88-induced activation of antiviral innate immunity in A549 cells.

Effect of tracheal intubation on postoperative complications in patients with pulmonary hypertension combined with non-cardiothoracic, non-obstetric surgery.

Endotracheal intubation can be associated with certain complications in certain group of patients. However, the relationship between endotracheal intubation and postoperative complications is unclear in patients with pulmonary hypertension (PHTN). This study evaluated the relationship between endotracheal intubation and postoperative complications in non-cardiothoracic and non-obstetric surgery patients with PHTN. A secondhand analysis of non-cardiothoracic, non-obstetric procedures was performed on patients with PHTN between 2007 and 2013 in a hospital at the University of Washington. Multivariable logistic regression analyses were used to calculate the adjusted odds ratios to estimate the association between anesthesia and 30-day postoperative complications. Interaction and stratified analyses were conducted according to the American Society of Anesthesiologists score (ASA), smoking, hypertension, and open surgical approach. A total of 573 patients were included in this study, and the mean age was 60.3; 54% were male. In a multivariate regression model for patients with non-cardiothoracic, non-obstetric surgery combined with PHTN, the risk of 30-day postoperative complications was higher in the tracheal intubation group than in patients with non-intubated anesthesia after adjusting for potential covariates (adjusted odds ratio = 2.47; 95% CI, 1.28-4.78). However, there was no significant difference in postoperative mortality between these groups. Statistical analysis showed no interaction between the variables of tracheal intubation and 30-day postoperative complications. In this study, we found that tracheal intubation anesthesia is associated with increased risk of 30-day postoperative complications in PHTN patients undergoing non-cardiothoracic, non-obstetric surgery. Further studies are needed to confirm our findings.

Network Pharmacology-Based Analysis on the Action Mechanism of Oleanolic Acid to Alleviate Osteoporosis.

Oleanolic acid (OA) is a triterpenoid commonly found in plants and has shown extensive pharmaceutical activities. This study aimed to investigate the underlying mechanism of antiosteoporosis (OP) action of OA by utilizing the network pharmacology approach and molecular docking methods. First, the targets of OA were identified using the GeneCards, Stitch, and Swisstarget databases, and the targets related to OP were mined using the NCBI, Genecards, and DisGeNet databases. The overlapped targets of OA and OP were regarded as candidate targets, and the String database was used to obtain the protein-protein interactions among the targets. Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment pathways of the candidate targets were performed using the DAVID database. In addition, the top 16 targets in the protein interaction network were used for molecular docking. Finally, an animal model constructed using d-galactose-induced oxidative stress and a low-calcium diet with accelerated bone loss was used to verify the in vivo effects of OA on osteoporotic mice. A total of 42 candidate targets for OA to treat OP were obtained. According to the protein-protein interaction network, MAPK1 showed the highest connectivity with other proteins. Additionally, GO analysis identified the top 20 biological processes, 9 cellular components, and top 20 molecular functions. Moreover, the candidate targets were mainly involved in 13 signaling pathways such as TNF signaling pathway, insulin resistance, MAPK signaling pathway, apoptosis, and PI3K-Akt signaling pathways. Furthermore, molecular docking revealed that OA has a high degree of connections with 16 key proteins. In addition, the anti-OP effects of OA are further validated through the in vivo model. Altogether, our study elucidated the candidate targets for OA to alleviate OP, explored the protein-protein interactions and related signaling pathways of the targets, and validated the anti-OP effects of OA. It could provide a better understanding of the action mechanism in OA to treat OP.

Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties.

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 µg/mL) which is higher than dimethomorph (EC50 = 0.1148 µg/mL) and diacetylenyl amide (EC50 = 0.040 µg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.

Bisphosphonates and risk of cancers: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether bisphosphonates are associated with risk of cancers. Therefore, this meta-analysis aimed to evaluate the effect of bisphosphonates on overall cancers. METHODS: A search in Pubmed, Embase, Cochrane Library and Web of Science databases was conducted, from the inception date of each resource to September 26, 2019. The summarised effect estimates with 95% CIs were calculated using a random-effect model. Heterogeneity and publication bias were explored. RESULTS: Thirty-four articles were included in this study (4,508,261 participants; 403,196 cases). The results revealed that bisphosphonates significantly decreased the risk of colorectal cancer (RR = 0.89, 95% CI: 0.81-0.98), breast cancer (RR = 0.87, 95% CI: 0.82-0.93) and endometrial cancer (RR = 0.75, 95% CI: 0.61-0.94), but no significant association was observed in all-cause cancer. Furthermore, nitrogen-containing bisphosphonates only had protective effects both on breast cancer (RR = 0.94, 95% CI: 0.90-0.99) and endometrial cancer (RR = 0.70, 95% CI: 0.54-0.92). Non-nitrogen-containing bisphosphonates tended to increase the risk of liver cancer (RR = 2.14, 95% CI: 1.23-3.72) and pancreas cancer (RR = 1.75, 95% CI: 1.32-2.33). CONCLUSION: Bisphosphonates are significantly associated with risk reduction of colorectal, breast and endometrial cancer, especially nitrogen-containing bisphosphonates. It should be noted that non-nitrogen-containing bisphosphonates might increase the risk of liver and pancreas cancer. Large prospective cohort studies are needed to find the causal association between bisphosphonates and risk of cancers.

Proteomic analysis of halotolerant proteins under high and low salt stress in Dunaliella salina using two-dimensional differential in-gel electrophoresis.

Dunaliella salina, a single-celled marine alga with extreme salt tolerance, is an important model organism for studying fundamental extremophile survival mechanisms and their potential practical applications. In this study, two-dimensional differential in-gel electrophoresis (2D-DIGE) was used to investigate the expression of halotolerant proteins under high (3 M NaCl) and low (0.75 M NaCl) salt concentrations. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatics were used to identify and characterize the differences among proteins. 2D-DIGE analysis revealed 141 protein spots that were significantly differentially expressed between the two salinities. Twenty-four differentially expressed protein spots were successfully identified by MALDI-TOF/TOF MS, including proteins in the following important categories: molecular chaperones, proteins involved in photosynthesis, proteins involved in respiration and proteins involved in amino acid synthesis. Expression levels of these proteins changed in response to the stress conditions, which suggests that they may be involved in the maintenance of intracellular osmotic pressure, cellular stress responses, physiological changes in metabolism, continuation of photosynthetic activity and other aspects of salt stress. The findings of this study enhance our understanding of the function and mechanisms of various proteins in salt stress.

Effects of folic acid supplementation during different pregnancy periods and relationship with the other primary prevention measures to neural tube defects.

OBJECTIVE: To find out the prevention effects of folic acid supplements during different pregnancy periods on neural tube defects (NTDs) and the relationship of folic acid supplements with the other NTDs' primary preventive measures. METHODS: A 1:1 case-control study was conducted. Four hundred and fifty-nine women who delivered or gestate infants/fetuses with NTDs in the last two years were randomly selected as cases and were matched with women who delivered babies without obvious birth defects as controls. RESULTS: For anencephaly, folic acid supplementation during the periconceptional period and preconceptional period has a 57-83% reduction in risk of NTDs(ORs ranged from 0.17 to 0.43). For spina bifida, folic acid supplementation during the periconceptional period has a 79% reduction in risk of NTDs (OR = 0.21). For encephalocele, folic acid supplementation during the periconceptional period has a 67% reduction in risk of NTDs (OR = 0.33). The prevention effects on NTDs were significant when these preventive measures combined with folic acid supplements during the periconceptional period, with OR 0.04, 0.07, 0.10 and 0.11. CONCLUSION: The specific effects of folic acid supplementation during different periods show the reduction in the risk of NTDs, anencephaly, spina bifida, encephalocele. During periconceptional period, folic acid supplements have preventive effects on all NTDs' subtypes.

Glutathione homeostasis and Cd tolerance in the Arabidopsis sultr1;1-sultr1;2 double mutant with limiting sulfate supply.

KEY MESSAGE: Cadmium sensitivity in sultr1;1 - sultr1;2 double mutant with limiting sulfate supply is attributed to the decreased glutathione content that affected oxidative defense but not phytochelatins' synthesis. In plants, glutathione (GSH) homeostasis plays pivotal role in cadmium (Cd) detoxification. GSH is synthesized by sulfur (S) assimilation pathway. Many studies have tried to investigate the role of GSH homeostasis on Cd tolerance using mutants; however, most of them have focused on the last few steps of S assimilation. Until now, mutant evidence that explored the relationship between GSH homeostasis on Cd tolerance and S absorption is rare. To further reveal the role of GSH homeostasis on Cd stress, the wild-type and a sultr1;1-sultr1;2 double mutant which had a defect in two distinct high-affinity sulfate transporters were used in this study. Growth parameters, biochemical or zymological indexes and S assimilation-related genes' expression were compared between the mutant and wild-type Arabidopsis plants. It was found that the mutations of SULTR1;1 and SULTR1;2 did not affect Cd accumulation. Compared to the wild-type, the double mutant was more sensitive to Cd under limited sulfate supply and suffered from stronger oxidative damage. More importantly, under the same condition, lower capacity of S assimilation resulted in decreased GSH content in mutant. Faced to the limited GSH accumulation, mutant seedlings consumed a large majority of GSH in pool for the synthesis of phytochelatins rather than participating in the antioxidative defense. Therefore, homeostasis of GSH, imbalance between antioxidative defense and severe oxidative damage led to hypersensitivity of double mutant to Cd under limited sulfate supply.

The effects of preconception examinations on neural tube defects and the primary preventive measures: case-control study.

BACKGROUND: Preventive measures for neural tube defects (NTDs) have been recommended for many years in China, but the compliance with these measures is unsatisfactory. This study aims to analyze the effects of preconception examinations on NTDs and its primary preventive measures. METHODS: A 1:1 hospital-based case-control study was conducted. Four hundred and fifty-nine women who delivered or gestate infants/fetuses with NTDs from January 2006 to December 2008 were randomly selected and matched with women who delivered babies without obvious birth defects as controls in Shandong and Shanxi province. Multivariate conditional logistic regression was adopted. RESULTS: Significant associations were shown between preconception examinations (OR = 0.461), health education (OR = 0.336), periconceptional folic acid supplement (OR = 0.295), periconceptional rational diet adjustment (OR = 0.278) and NTDs. In the case group, the rates of periconceptional folic acid supplement and health education conduction by women who had preconception examinations were significantly higher than that of those who had not, OR being 3.04 and 4.55, respectively (p < 0.05). Among the preventive effects on NTDs, preconception examinations and other NTDs primary preventive measures had significant combined effects and the combined effects with periconceptional folic acid supplement were the greatest, with OR of 0.04. CONCLUSION: Preconception examinations have preventive effects on NTDs and can significantly improve the compliance of other NTDs primary preventive measures. In addition, preconception examinations and these measures have synergetic prevention effects, indicating the critical role played by preconception examinations on NTDs prevention.

Maternal consumption of non-staple food in the first trimester and risk of neural tube defects in offspring.

To study the associations between maternal consumption of non-staple food in the first trimester and risk of neural tube defects (NTDs) in offspring. Data collected from a hospital-based case-control study conducted between 2006 and 2008 in Shandong/Shanxi provinces including 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models were used to examine the associations between maternal consumption of non-staple food in the first trimester and risk of NTDs in offspring. The effects were evaluated by odds ratio (OR) and 95% confidence intervals (95% CIs) with SAS9.1.3.software. Maternal consumption of milk, fresh fruits and nuts in the first trimester were protective factors for total NTDs. Compared with consumption frequency of ˂1 meal/week, the ORs for milk consumption frequency of 1-2, 3-6, ≥7 meals/week were 0.50 (95% CI: 0.28-0.88), 0.56 (0.32-0.99), and 0.59 (0.38-0.90), respectively; the ORs for fresh fruits consumption frequency of 1-2, 3-6, ≥7 meals/week were 0.29 (95% CI: 0.12-0.72), 0.22 (0.09-0.53), and 0.32 (0.14-0.71), respectively; the ORs for nuts consumption frequency of 1-2, 3-6, ≥7 meals/week were 0.60 (95% CI: 0.38-0.94), 0.49 (0.31-0.79), and 0.63 (0.36-1.08), respectively. Different effects of above factors on NTDs were found for subtypes of anencephaly and spina bifida. Maternal non-staple food consumption of milk, fresh fruits and nuts in the first trimester was associated with reducing NTDs risk in offspring.

Nausea and vomiting in early pregnancy and the risk of neural tube defects: a case-control study.

There has been considerable professional debate on the association between nausea and vomiting in early pregnancy (NVP) and neural tube defects (NTDs) risk. This study explored the association between NVP and NTDs risk, and the effect of folic acid supplements on the association. A 1:1 matched case-control study was conducted and conditional logistic regression model was used to analyze the associations. The result showed the odds ratio (OR) of severe NVP for NTDs was 2.403 (95%CI 1.437,4.017; P<0.001) and that of moderate NVP was 1.469 (95%CI 1.063,2.031; P = 0.020) compared with light NVP when adjusted by the potential confounders. Stratified by intake of folic acid supplements, the ORs for severe and moderate NVP turned to 2.147 (95%CI 1.140, 4.043; P = 0.018) and 2.055 (95%CI 1.320, 3.199; P = 0.001) in the stratum of non-intake of folic acid supplements while ORs reduced to 1.851 (95%CI 0.729, 4.699; P = 0.195) and 1.003 (95%CI 0.594, 1.694; P = 0.992) in the stratum of intake of folic acid supplements, respectively. We conclude that severe/moderate NVP has an association with the risk of NTDs, which was not found in the group with intake of folic acid supplements. Folic acid supplements should be recommended to use for the prevention of NTDs.

[Study on fluorescence labeling and determination of polypeptide (PC2~PC6) by high performance liquid chromatography].

This study was based on the thiol groups (-SH) of PC2~PC6, which could be reacted with the Monobromobimane (mBBr), in order to get polypeptide derivatives with fluorescent signal. A new method was developed for measuring the Polypeptides by high performance liquid chromatography with fluorescence detector, then the chromatographic conditions of HPLC was optimized; meawhile the reaction proportion of PCs and mBBr was identified by Trap-MS. The results showed that, the reaction proportion of PCs and mBBr was 1:1, the polypeptide derivatives had good stability; the five compounds separation was better, and the peak time focused on the 16.6~22.0 min; the linear correlation coefficient of PC2, PC3, PC4, PC5 and PC6 was >0.9991, and the limits of quantification were 0.3, 0.05, 0.3, 0.5 and 0.8 mg · L(-1) respectively, the recovery rate was 83.0%-102.0%; the method was reproducible, RSD<2%, this method for measuring the peptide compounds was rapid and accurate.

Maternal body mass index and the association between folic acid supplements and neural tube defects.

AIM: To study the influence of maternal body mass index (BMI) on the association between folic acid supplementation and neural tube defects (NTDs) risk in offspring. METHODS: A hospital-based, case-control study was conducted between 2006 and 2008 on 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models examined the associations between folic acid supplementation and the NTDs risk in offspring for all mothers, underweight/normal weight mothers (BMI<24.0) and overweight/obese mothers (BMI ≥24.0). The effects were evaluated by adjusted odds ratio (AOR) and 95% confidence intervals (CIs) with SAS 9.1.3 software. RESULTS: The overall AOR for periconceptional folic acid supplementation was 0.315 (95% CI = 0.172-0.577) when compared with no supplements. Stratified by maternal BMI, the AOR for periconceptional folic acid supplementation in overweight/obese mothers was greater than in underweight/normal weight mothers (0.646 vs. 0.208). The AOR for folic acid supplementation within 3 months before conception was 0.711 (95% CI = 0.323-1.563) in all mothers. Stratified by maternal BMI, the AOR for folic acid supplementation within 3 months before conception in overweight/obese mothers was greater than in underweight/normal weight mothers (0.658 vs. 0.527). CONCLUSION: The association between folic acid supplementation and the reduced NTDs risk was weaker in overweight/obese mothers (BMI ≥24.0) than in underweight/normal weight mothers (BMI <24.0).

Maternal overweight and obesity and the risk of neural tube defects: a case-control study in China.

BACKGROUND: Studies have suggested that being obese before pregnancy is a risk factor for neural tube defects (NTDs), while results of many studies are controversial. This study aims to explore the association between maternal overweight and obesity before pregnancy and risk of NTDs. METHODS: A 1:1 matched case-control study was conducted. Cases were 459 women who delivered infants or conceived fetuses with NTDs in two provinces of China and controls were 459 women with live-born infants, without an apparent congenital malformation, matched with cases by region, delivery hospital, and year of childbirth. RESULTS: Compared with normal body weight, maternal obesity (body mass index, BMI ≥ 28 kg/m(2)) before pregnancy had a significant increased risk for NTDs as a group after adjusting for age, occupation, educational level, family income, parity, and use of folic acid (odds ratio, OR = 2.45; p < 0.05). No significant increase in NTD risk was found for maternal underweight (BMI < 18.5 kg/m(2)) and overweight (BMI from 24 to 28 kg/m(2)). For three subtypes of NTDs, anencephaly, spina bifida, and encephalocele, no significant increase in risk was found with maternal underweight, overweight, or obesity (all, p > 0.05). CONCLUSION: Maternal obesity before pregnancy is associated with risk of NTDs and should be considered in maternal reproductive health care.

Vertical characteristics of levels and potential sources of water-soluble ions in PM10 in a Chinese megacity.

To investigate the vertical characteristics of ions in PM10 as well as the contributions and possible locations of their sources, eight water-soluble ions were measured at four heights simultaneously along a meteorological tower in Tianjin, China. The total ion concentrations showed a general decreasing trend with increasing height, ranging from 64.94µgm(-3) at 10m to 44.56µgm(-3) at 220m. NH4(+), SO4(2-) and NO3(-) showed higher height-to-height correlations. In addition, relationships between ions are discussed using Pearson correlation coefficients and hierarchical clustering analysis (HCA), which implied that, for each height, the correlations among NH4(+), SO4(2-) and NO3(-) were higher. Finally, sources were identified qualitatively by the ratio of certain ions and quantitatively by principal component analysis/multiple linear regression (PCA/MLR) and positive matrix factorisation (PMF). Secondary sources played a dominant role for PM10 and water-soluble ions at four heights and became more important at greater heights (the percentage contributions were 43.04-66.41% for four heights by PCA/MLR and 46.93-67.62% by PMF). Then, the redistributed concentration field (RCF) combined with PCA/MLR and PMF was applied, which indicated the high potential source regions. The vertical characteristics of the levels, relationships, source contributions and locations would support the effective management of the water-soluble ions in particulate matter.

Periconceptional factors affect the risk of neural tube defects in offspring: a hospital-based case-control study in China.

OBJECTIVE: To explore the periconceptional factors affecting the risk of neural tube defects (NTDs), we carried out a hospital-based case-control study in China. METHODS: A 1:1 matched case-control study was conducted. With self-designed questionnaires, we solicited relevant information from 459 case mothers and 459 control mothers selected in two provinces of China through face-to-face interviews. Univariate and multivariate conditional logistic regression analyses were conducted to evaluate the effect values by odds ratios (ORs) and 95% confidence intervals (95%CIs) with SAS9.1.3.software. RESULTS: Daily passive tobacco smoke exposure was a risk factor for total NTDs (OR = 8.688, 95%CI = 2.329-32.404). Diet adjustment in the first trimester (OR = 0.061, 95%CI = 0.014-0.274), periconceptional folic acid intake (OR = 0.059, 95%CI = 0.011-0.321) and health education (OR = 0.251, 95%CI = 0.081-0.781) were protective factors for total NTDs. Differences in factors and their effects on NTDs were found for the three subtypes of NTDs: anencephaly, spina bifida and encephalocele. CONCLUSIONS: Daily passive tobacco smoke exposure, diet adjustment in the first trimester, periconceptional folic acid intake and health education were associated with NTDs.

Previous abortion and the risk of neural tube defects: a case-control study.

OBJECTIVE: To further explore the association between abortion history and neural tube defect (NTD) risk and the association of different interpregnancy intervals from prior abortion to current conception on NTD risk. STUDY DESIGN: A matched case-control study was conducted. Cases were 459 women who delivered and gestated babies/fetuses with NTDs in two provinces of China and 459 women with live-born infants, without an apparent congenital malformation, matched with cases by the same region, the same hospital, and childbirth in the same year as controls. All of the subjects were investigated by trained interviewers with the same criteria. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% CI of abortion history and interpregnancy intervals on NTD risk. RESULTS: Women with abortion history did not have an increased risk for spina bifida and encephalocele. The interpregnancy interval of < 6 months from prior abortion to current conception was significantly associated with anencephaly risk. CONCLUSION: Abortion with an interpregnancy interval of < 6 months from prior abortion to current conception may have an increased risk for anencephaly and should be considered in maternal reproductive health care.

[Study on the nuclear translocation mechanism in the inhibition of nuclear factor-ΚB activation in bacterial lipoprotein-tolerant THP-1 cells].

OBJECTIVE: To approach the nuclear factor-ΚB (NF-ΚB) nuclear translocation mechanism in bacterial lipoprotein (BLP) tolerance. METHODS: Human monocytic THP-1 cells were first pretreated with 10, 100, 1 000 ng/ml BLP for 20 hours to induce BLP tolerance. Then THP-1 cells without BLP pretreatment (control group) or with BLP pretreatment (tolerance group) were stimulated with 0, 10, 100, 1 000 ng/ml BLP again for 6 hours. The tumor necrosis factor-α (TNF-α) content in culture medium was measured by enzyme linked immunosorbent assay (ELISA) in order to determine the most suitable BLP pretreatment and stimulation concentration. Western blotting was used to detect the protein level, nuclear translocation and phosphorylation of NF-ΚB p50 and p65 in the cells of control and tolerance groups treated with respective conditions for 0, 0.5, 1, 2 and 6 hours. RESULTS: In control group BLP stimulation (10, 100, 1 000 ng/ml) could induce THP-1 activation and TNF-α production (pg/ml: 184.86±32.51, 3 215.88±167.09, 6 042.96±245.37) in a dose-dependent manner. In tolerance group, 100 ng/ml BLP pretreatment resulted in almost complete inhibition of TNF-α production as induced by 101 000 ng/ml BLP stimulation. Therefore, 100 ng/ml BLP pretreatment and 1 000 ng/ml stimulation were selected for following cell treatment. Western blotting analysis showed that there was an increase of p50 protein level in BLP-tolerant cells comparing with control group (0 hour: 542.9±15.6 vs. 272.8±13.2, 0.5 hour: 558.0±16.9 vs. 236.4±11.8, 1 hour: 524.7±17.5 vs. 211.6±9.8, 2 hours: 584.9±15.6 vs. 222.4±12.3, all P<0.01), whereas the p65 protein level was similar between the two groups. BLP stimulation also induced the nuclear translocation of p50 and p65 in control group (1-hour p50: 344.2±13.6 vs. 79.0±5.2, p65: 78.4±4.5 vs. 0, both P<0.05), but not in tolerance group. In addition, the phosphorylation of p65 at serine 536 was induced after BLP stimulation in control THP-1 cells (0.5 hour: 0.67±0.08 vs. 0.04±0.01, 1 hour: 0.71±0.11 vs. 0.04±0.01, both P<0.05), but this change was not detected in BLP-tolerant cells. CONCLUSION: It was found that in BLP-tolerant cells, the expression of inhibitory subunit p50 was increased and the nuclear translocation and phosphorylation of p65 with trans-activation ability was inhibited. These changes are likely responsible for the reduced gene expression of NF-ΚB dependent genes in BLP-tolerant cells.

A case-control study of the effects of pregnancy planning on neural tube defects and its primary preventive measures.

BACKGROUND: Measures for prevention of neural tube defects (NTDs) have been recommended for many years in China, but the compliance with these measures is unsatisfactory. This study aims to compare the effect differences between planned pregnancy and unplanned pregnancy in the compliance with these measures and analyze the interactions between pregnancy planning and these measures for NTD prevention. METHODS: A 1:1 matched case-control study was conducted. We randomly selected 349 women who delivered or gestated babies/fetuses with NTDs in the last two years in two provinces and matched them with 349 women who delivered babies without obvious birth defects as controls. RESULTS: In the case group, 99 women reported that they had planned their pregnancies, accounting for 28.4%, and the proportion who received preconception examinations and took folic acid prior to conception was 13.8 and 8.6%, respectively. According to the multivariate analysis, health education (odds ratio [OR], 0.350), preconception examinations (OR, 0.497) and folic acid consumption prior to conception (OR, 0.257) all had preventative effects on NTDs (for all, p < 0.05). In both groups, the proportions of women who received preconception examinations and reported folic acid intake were much higher for those who reported planning their pregnancies compared to women with an unplanned pregnancy (for all, p < 0.01); and for NTD prevention, synergistic interactions existed between pregnancy planning and the other preventive measures. CONCLUSION: Folic acid consumption prior to conception, preconception examinations, and health education have preventive effects on NTDs. Pregnancy planning can significantly promote compliance with these preventive behaviors. In addition, there are synergistic interactions between pregnancy planning and these measures.