Targeted metabolomics profiling in pregnancy associated with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is common in pregnancy, however, its effects has not been fully elucidated. Here, we conducted targeted metabolomics profiling to study the relationship. METHODS: This study enrolled 111 pregnant women, including sufficient group (n = 9), inadequate group (n = 49) and deficient group (n = 53). Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabonomics were used to characterize metabolite profiles associated with vitamin D deficiency in pregnancy. RESULTS: Many metabolites decreased in the inadequate and deficient group, including lipids, amino acids and others. The lipid species included fatty acyls (FA 14:3, FA 26:0; O), glycerolipids (MG 18:2), glycerophospholipids (LPG 20:5, PE-Cer 40:1; O2, PG 29:0), sterol lipids (CE 20:5, ST 28:0; O4, ST 28:1; O4). Decreased amino acids included aromatic amino acids (tryptophan, phenylalanine, tyrosine) and branched-chain amino acids (valine, isoleucine, leucine), proline, methionine, arginine, lysine, alanine, L-kynurenine,5-hydroxy-L-tryptophan, allysine. CONCLUSIONS: This targeted metabolomics profiling indicated that vitamin D supplementation can significantly affect lipids and amino acids metabolism in pregnancy.

Evolution of Electrocatalytic CO2 Reduction Activity Induced by Charge Segregation in Atomically Precise AuAg Nanoclusters Based on Icosahedral M13 Unit 3D Assembly.

The precise self-assembly of building blocks at atomic level provides the opportunity to achieve clusters with advanced catalytic properties. However, most of the current self-assembled materials are fabricated by 1/2D assembly of blocks. High dimensional (that is, 3D) assembly is widely believed to improve the performance of cluster. Herein, the effect of 3D assembly on the activity for electrocatalytic CO2 reduction reaction (CO2 RR) is investigated by using a range of clusters (Au8 Ag55 , Au8 Ag57 , Au12 Ag60 ) based on 3D assembly of M13 unit as models. Although three clusters have almost the same sizes and geometric structures, Au8 Ag55 exhibits the best CO2 RR performance due to the strong CO2 adsorption capacity and effective inhibition of H2 evolution competition reaction. The deep insight into the superior activity of Au8 Ag55 is the unique electronic structure attributed to the charge segregation. This study not only demonstrates that the assembly mode greatly affects the catalytic activity, but also offers an idea for rational designing and precisely constructing catalysts with controllable activities.

UHPLC-MS/MS-Based Metabolomics and Clinical Phenotypes Analysis Reveal Broad-Scale Perturbations in Early Pregnancy Related to Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy, with adverse effects on both mother and fetus. The establishment of early diagnosis and risk assessment model is of great significance for preventing and reducing adverse outcomes of GDM. In this study, the broad-scale perturbations related to GDM were explored through the integration analysis of metabolic and clinical phenotypes. Maternal serum samples from the first trimester were collected for targeted metabolomics analysis by using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Statistical analysis was conducted based on the levels of the 184 metabolites and 76 clinical indicators from GDM women (n =60) and matched healthy controls (n =90). Metabolomics analysis revealed the down-regulation of fatty acid oxidation in the first trimester of GDM women, which was supposed to be related to the low serum level of dehydroepiandrosterone.While the significantly altered clinical phenotypes were mainly related to the increased risk of cardiovascular disease, abnormal iron metabolism, and inflammation. A phenotype panel established from the significantly changed serum indicators can be used for the early prediction of GDM, with the area under the receiver-operating characteristic curve (ROC) 0.83. High serum uric acid and C-reaction protein levels were risk factors for GDM independent of body mass indexes, with ORs 4.76 (95% CI: 2.08-10.90) and 3.10 (95% CI: 1.38-6.96), respectively. Predictive phenotype panel of GDM, together with the risk factors of GDM, will provide novel perspectives for the early clinical warning and diagnosis of GDM.

Effects of Diet and Exercise Interventions to Prevent Gestational Diabetes Mellitus in Pregnant Women With High-Risk Factors in China: A Randomized Controlled Study.

This is a randomized controlled study to determine whether diet and exercise interventions can reduce the incidence of gestational diabetes mellitus (GDM) in pregnant women with high-risk factors. Ninety-four pregnant women were randomly divided into the intervention (n = 47) and control (n = 47) groups. A diet and exercise program was provided for the intervention group by researchers and was adjusted every 2 weeks by outpatient or WeChat intervention. The control group only received the routine health management in the hospital. Follow-up continued until the birth of the baby. The incidence of GDM (23.9%) in the intervention group was lower than in the control group (51.1%) (p = .007). Weight gain did not differ significantly between the two groups throughout pregnancy (p = .572). It is concluded that diet and exercise interventions can reduce the incidence of GDM in pregnant women with high-risk factors.

[Effect of Mobile Health for Standardized Management on Women with Gestational Diabetes Mellitus].

Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.The glycemic control rate and the incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit were compared between the two groups. Results The glycemic control rate in mobile health management group was significantly higher than that in the traditional management group [(67.22±22.76)% vs.(60.69±21.28)%,P=0.004].The incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit demonstrated no significant differences between groups(all P > 0.05). Conclusions Mobile health applied in standardized management is conducive to the glycemic control of GDM women,whereas it does not significantly improve the pregnancy outcomes.Due to the short time of intervention,the effects of mobile health on pregnancy outcomes need further study.

Metabolic profiling in early pregnancy and associated factors of folate supplementation: A cross-sectional study.

BACKGROUND: Pregnancy generally alters the balance of maternal metabolism, but the molecular profiles in early pregnancy and associated factors of folate supplementation in pregnant women remains incompletely understood. METHODS: Untargeted metabonomics based on high-performance liquid chromatography-high-resolution mass spectrometry integrated with multivariate metabolic pathway analysis were applied to characterize metabolite profiles and associated factors of folate supplements in early pregnancy. The metabolic baseline of early pregnancy was determined by metabolic analysis of 510 serum samples from 131 non-pregnant and 379 pregnant healthy Chinese women. The pathophysiology of adaptive reactions and metabolic challenges induced by folate supplementation in early pregnancy was further compared between pregnant women with (n = 168) and without (n = 184) folate supplements. RESULTS: Compared with non-pregnant participants, 106 metabolites, majority of which are related to amino acids and lysophosphatidylcholine/phosphatidylcholine, and 13 metabolic pathways were significantly changed in early pregnancy. The supplementation of folate in early pregnancy induced marked changes in N-acyl ethanolamine 22:0, N-acyl taurine 18:2, glycerophosphoserine 44:1 and 8,11,14-eicosatrienoate, proline, and aminoimidazole ribotide levels. CONCLUSIONS: During early pregnancy, the metabolism of amino acids significantly changes to meet the physiological requirements of pregnant women. Folate intake may change glucose and lipid metabolism. These findings provide a comprehensive landscape for understanding the basic characteristics and gestational metabolic networks of early pregnancy and folate supplementation. This study provides a basis for further research into the relationship between metabolic markers and pregnancy diseases. TRIAL REGISTRATION: This study protocol was registered on www.ClinicalTrials.gov, NCT03651934, on August 29, 2018 (prior to recruitment).

Associations of Serum Selenium Levels in the First Trimester of Pregnancy with the Risk of Gestational Diabetes Mellitus and Preterm Birth: a Preliminary Cohort Study.

Women with gestational diabetes mellitus (GDM) may have lower serum selenium levels than healthy controls, which may be associated with preterm birth. We explored the association of serum selenium levels in early pregnancy with the risk of GDM and preterm birth among Chinese women. We included 398 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Serum selenium levels were measured in the first trimester. After delivery, data concerning mothers and their children were sourced from medical records by researchers who were blind to the participants' selenium status. Of the 398 women, 71 (17.8%) had GDM, 21(5.3%) had preterm birth, and 266 (66.8%) had selenium deficiency (serum selenium < 70 µg/L). Women in the upper three quartiles of serum selenium level did not have a significantly lower risk of GDM or preterm birth than those in the lowest quartile after adjustment for covariates (all p > 0.05). When serum selenium levels were classified as normal or deficient, the risk of GDM or preterm birth among women with normal serum selenium levels was still not lower than that of women with deficient serum selenium levels after adjustment for covariates (all p > 0.05). Although selenium deficiency was common in the Chinese women in our cohort, our results indicate that low serum selenium level during early pregnancy may not be a strong predictor of the risk of GDM and preterm birth. However, our sample size was small, and future studies with larger populations are warranted.

Associations of TMPRSS6 Polymorphisms with Gestational Diabetes Mellitus in Chinese Han Pregnant Women: a Preliminary Cohort Study.

Body iron status is likely to be associated with type 2 diabetes (T2DM) and gestational diabetes mellitus (GDM); transmembrane protease serine 6 (TMPRSS6) polymorphisms may be associated with T2DM risk through their effects on body iron status. However, it remains unknown whether the TMPRSS6 single nucleotide polymorphisms (SNPs) affect the risk of GDM development. We aimed to determine whether the TMPRSS6 SNPs rs855791 (V736A) and rs4820268 (D521D) are associated with the risk of GDM in pregnant women. The two SNPs in TMPRSS6 gene were genotyped and examined for their associations with body iron status and GDM risk in 398 unrelated Chinese Han pregnant women. The 2 TMPRSS6 SNPs rs855791 and rs4820268 were both significantly associated with serum iron and transferrin saturation (P < 0.01 for all) rather than ferritin. After adjustment for covariates, the C allele of rs4820268 was nominally and significantly associated with an increased risk of GDM (OR = 2.531; 95%CI = 1.044-6.136, P = 0.040); when concentrations of ferritin were further adjusted, the association was still significant (OR = 2.528; 95%CI = 1.043-6.126, P = 0.040). There was a significant trend (P = 0.065) in the association between the T allele of rs855791 and an increased GDM risk in this study population. The 2 TMPRSS6 SNPs rs855791 and rs4820268 were both significantly associated with serum iron and transferrin saturation, and TMPRSS6 variants might be associated with the risk of GDM. Furthermore, the effects of TMPRSS6 SNPs on the risk of GDM may not be completely explained by the mediation of body iron status. Further studies are warranted.

Vascular Endothelial Growth Factor-Transfected Bone Marrow Mesenchymal Stem Cells Improve the Recovery of Motor and Sensory Functions of Rats With Spinal Cord Injury.

STUDY DESIGN: Basic science. OBJECTIVE: The aim of this study was to examine the effect of vascular endothelial growth factor (VEGF)-transfected bone marrow mesenchymal stem cells (BMSCs) on the recovery of motor and sensory functions of rats with spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: There is no effective treatment to protect against SCI. BMSCs have been widely applied to the treatment of nervous system damage due to the function of prompt neurite growth and inhibition of demyelination following injury. METHODS: VEGF-transfected BMSCs were injected to rats with SCI and the recovery of motor and sensory functions was observed. The Basso, Beattie, and Bresnahan, mechanical withdrawal threshold and thermal withdraw latency grading was conducted to assess the recovery status of motor and sensory functions of the SCI rats. The expression of VEGF, CD31, and NF200 was detected by immunofluorescence. RESULTS: The recovery of the rat motor and sensory functions in the VEGF-transfected BMSC (BMSC-VEGF) group was higher than those of the other groups with the exception of the Sham group (P < 0.05). The expression of the CD31 and NF200 proteins in the rat SCI regions was the highest in the BMSC-VEGF group, whereas the survival of BMSC in the BMSC-VEGF group was increased compared with that in the BMSC-Ad group. In addition, the injection of VEGF-transfected BMSCs can improve the angiogenesis of the injured area and retain the survival of injected cells and neurons. CONCLUSION: The injection of BMSC-VEGF improved the recovery of motor function in SCI rats. LEVEL OF EVIDENCE: N/A.

[Changes in plasma levels of atrial natriuretic peptide, endothelin-1 and von Willebrand factor among newborns with persistent pulmonary hypertension].

OBJECTIVE: To investigate the changes in plasma levels of atrial natriuretic peptide (ANP), endothelin-1 (ET-1) and von Willebrand factor (vWF), and their significance among newborns with persistent pulmonary hypertension (PPH). METHODS: Sixty-six newborns with PPH (case group) (mild: 26 cases; moderate: 21 cases; severe: 19 cases), as well as 40 newborns without PPH (control group) who were hospitalized in the same period, were enrolled. The control group underwent echocardiography on admission. The case group underwent echocardiography before treatment (with refractory hypoxemia) and after 7 days of treatment for measurement of pulmonary artery systolic pressure (PASP). Meanwhile, plasma levels of ANP, ET-1 and vWF were measured using ELISA. RESULTS: Before treatment, the case group had significantly higher plasma levels of ANP, ET-1 and vWF than the control group (P<0.05), and these indices increased as PASP rose. After 7 days of treatment, the children with mild or moderate PPH showed normal PASP, and their plasma levels of ANP, ET-1 and vWF were not significantly different from those of control group. The children with severe PPH had significant decreases in all indices, but they were significantly higher than those of the control group. Plasma levels of ANP, ET-1 and vWF were significantly positively correlated with PASP before and after treatment (P<0.01). CONCLUSIONS: Changes in plasma levels of ANP, ET-1 and vWF can reflect PASP in newborns with PPH during treatment. Dynamic monitoring of these indices can help to judge the severity of PPH and guide treatment.

Effect of aqueous extract and fractions of Zhi-Zi-Hou-Pu decoction against depression in inescapable stressed mice: Restoration of monoamine neurotransmitters in discrete brain regions.

CONTEXT: Zhi-Zi-Hou-Pu decoction (ZZHPD) is a traditional prescription which has been used to treat "Yu-syndrome" (depression and melancholia) in Chinese herbal medication. OBJECTIVE: To evaluate antidepressant activities of ZZHPD, its fractions and possible mechanism(s) of action. MATERIALS AND METHODS: ZZHPD (1241, 2482 and 4964 mg/kg), n-butanol fraction (ZH-BA, 1454 mg/kg), cyclohexane fraction (ZH-CH, 17 mg/kg) and aqueous fraction (ZH-AQ, 3493 mg/kg) were administered orally to different groups of mice for seven consecutive days. Forced Swimming Test (FST) and Tail Suspension Test (TST) were conducted 60 min after the last administration to evaluate the antidepressant effect. Norepinephrine, dopamine and 5-hydroxytryptamine levels in discrete brain parts were determined by HPLC-FD immediately after behavioral tests. RESULTS: ZZHPD at 2482, 4964 mg/kg, ZH-BA (1454 mg/kg), ZH-CH (17 mg/kg) or clomipramine hydrochloride (20 mg/kg) significantly (p < 0.05) reduced the duration of immobility in FST and TST without affecting locomotor activities in the open field test. Observed from score plot of principle component analysis of monoamine levels in different groups, the monoamine profile of ZZHPD-treated mice were similar to that of the normal control mice. HPLC-UV analysis indicated that iridoid glycosides, flavones and neolignans might be the active chemicals. DISCUSSION AND CONCLUSION: The results demonstrated significant antidepressant-like effect of ZZHPD in mice which was related to monoaminergic system, ZH-BA and ZH-CH could be the active fractions responsible for the antidepressant effect of ZZHPD.