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.

Effect of vitamin D supplementation on glycose homeostasis and islet function in vitamin D deficient or insufficient diabetes and prediabetes: a systematic review and meta-analysis.

Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25-dihydroxyvitamin D [25(OH)D]<30 ng/ml were included. All data were analyzed and presented based on the Cochrane guidelines and PRISMA guidelines. In total, 27 articles (n = 1,932) were enrolled in this study. Vitamin D supplementation significantly improved fasting blood glucose, postprandial blood glucose, and quantitative insulin sensitivity check index in diabetes and prediabetes with baseline 25(OH)D<30 ng/ml. Higher percentages regressing from prediabetes to normal glucose status [1.60 (1.19, 2.17), p = 0.002, n = 564] and lower percentage progressing from prediabetes to diabetes [0.68 (0.36, 1.27), p = 0.23, n = 569] were found in the supplementation group. The positive effects of vitamin D supplementation on body mass index, waist, HDL-C, LDL-C, and CRP were also demonstrated. In conclusion, modest improvements in vitamin D supplementation on short-term glycose homeostasis, insulin sensitivity, and disease development in diabetes and prediabetes with 25(OH)D<30 ng/ml were demonstrated, but more research needs to be conducted in the future to support the clinical application. (Register ID: CRD42020186004).

Maternal factors associated with neonatal vitamin D deficiency.

Background An adequate maternal vitamin D (vitD) intake is rarely achieved in actual practice. The aim of this study was to assess maternal factors associated with neonatal vitD deficiency. Methods This is a single-institution prospective case-control study. Consecutive single-birth neonates admitted between September 2014 and February 2015 were prospectively enrolled. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by spectrometry. The associations between neonatal vitD deficiency (defined as 25(OH)D <15 ng/mL) and several maternal characteristics, including body mass index (BMI) at delivery, education, health insurance status, birth season, sun exposure time, egg consumption, and vitD supplementation during pregnancy, were examined using multivariable logistic regression and their respective odds ratios (ORs) reported. Results A total of 125 mother-infant dyads were enrolled, with a gestational age of 36.8±2.7 weeks. Fifty-six percent (70/125) of the neonates had vitD deficiency. Maternal factors that were significantly associated with vitD deficiency included winter birth, insufficient sun exposure time, high maternal BMI at delivery, insufficient egg consumption, insufficient vitD supplementation during pregnancy, and disadvantaged health insurance. Disadvantaged insurance status and insufficient vitD supplementation during pregnancy were the two most influential factors of neonatal vitD deficiency, with an OR of 7.5 (95% confidence interval [CI], 2.0-37.6) and 7.0 (95% CI, 2.7-20.7), respectively. Conclusions Neonatal vitD deficiency is very rampant. An individualized vitD supplementation strategy may be developed by taking into consideration pregnant women's socioeconomic status and lifestyles.

E-cadherin Mediates the Preventive Effect of Vitamin D3 in Colitis-associated Carcinogenesis.

Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D3 at different dosages (15, 30, 60 IU·g·w), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D3 groups compared with the control group after inhibition of expression of ß-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D3 reduced the transcriptional activity and nuclear level of ß-catenin, and it also increased E-cadherin expression and its binding affinity for ß-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D3 in mouse colons. Taken together, our results indicate that vitamin D3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D3 on ß-catenin activity.

Strong Negative Interference by Calcium Dobesilate in Sarcosine Oxidase Assays for Serum Creatinine Involving the Trinder Reaction.

The vasoprotective drug calcium dobesilate is known to interfere with creatinine (Cr) quantifications in sarcosine oxidase enzymatic (SOE) assays. The aim of this study was to investigate this interference in 8 different commercially available assays and to determine its clinical significance. In in vitro experiments, interference was evaluated at 3 Cr levels. For this, Cr was quantified by SOE assays in pooled serum supplemented with calcium dobesilate at final concentrations of 0, 2, 4, 8, 16, 32, and 64 µg/mL. Percent bias was calculated relative to the drug-free specimen. For in vivo analyses, changes in serum concentrations of Cr, cystatin C (CysC; a renal function marker), and calcium dobesilate were monitored in healthy participants of group I before and after oral calcium dobesilate administration. In addition, variations in interference were also examined among different SOE assays using serum obtained from healthy participants of group II. Lastly, Cr levels from the 10 patients treated with calcium dobesilate were measured using 4 SOE assays and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) for comparison. Our in vitro analyses indicated that the presence of 8 µg/mL calcium dobesilate resulted in a -4.4% to -36.3% reduction in Cr serum concentration compared to drug-free serum for 8 SOE assays examined. In vivo, Cr values decreased relative to the baseline level with increasing drug concentration, with the lowest Cr levels obtained at 2 or 3 hours after drug administration in participants of group I. The observed Cr concentrations for participants in group II were reduced by -28.5% to -3.1% and -60.5% to -11.6% at 0 and 2 hours after administration related to baseline levels. The Cr values of 10 patients measured by Roche, Beckman, Maker, and Merit Choice SOE assays showed an average deviation of -20.0%, -22.4%, -14.2%, and -29.6%, respectively, compared to values obtained by LC-IDMS/MS. These results revealed a clinically significant negative interference with calcium dobesilate in all sarcosine oxidase-based Cr assays, but the degree of interference varied greatly among the assays examined. Thus, extra care should be taken in evaluating Cr quantification obtained by SOE assays in patients undergoing calcium dobesilate therapy.

Preparation of liposomes containing zedoary turmeric oil using freeze-drying of liposomes via TBA/water cosolvent systems and evaluation of the bioavailability of the oil.

The purpose of this study was to enhance the absorption of zedoary turmeric oil (ZTO) in vivo and develop new formulations of a water-insoluble oily drug. This study described a method for preparing ZTO liposomes, which involved freeze-drying (FD) of liposomes with TBA/water cosolvent systems. The TBA/water cosolvent systems were used to investigate a feasible method of liposomes manufacture; the two factors, sugar/lipid mass ratio and TBA content (concentration), of the preparation process were evaluated in this study. The results showed that the addition of TBA content could significantly enhance the sublimation of ice resulting in short FD cycles time, and reduce the entrapment efficiency of liposomes. In addition, the residual TBA solvents levels were determined to be less than 0.37% under all optimum formulations and processing conditions. Several physical properties of liposomes were examined by H-600 transmission electron microscope (TEM) and zetamaster analyser system. The results revealed that the liposomes were smooth and spherical with an average particle size of 457 +/- 7.8 nm and the zeta potential was more than 3.65 Mv. The bioavailability of the liposomes was evaluated in rabbits, compared with the conventional self-emulsifying formulation for oral administration. Compared with the conventional self-emulsifying formulation, the plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the liposomes with a bioavailability of 257.7% (a good strategy for improving the bioavailability of an oily drug). In conclusion, the present experimental findings clearly demonstrated the usefulness of ZTO liposome vesicles in improving therapeutic efficacy by enhancing oral bioavailability. Our study offered an alternative method for designing sustained-release preparations of oily drugs.