Effect of vitamin D supplementation on glucose control in mid-late gestation: A randomized controlled trial.

BACKGROUND & AIMS: It is unclear whether vitamin D supplementation contributes to gestational glucose control and whether the specific effects vary in individuals with diverse genetic and metabolic contexts. The study aimed to assess the effect of vitamin D supplementation during pregnancy on subsequent glucose levels and to identify factors modulating the response to vitamin D3 intake. METHODS: We conducted a multicenter randomized controlled trial, 1720 pregnant women recruited from the three antenatal clinics of Hefei city, China, who were allocated to receive either 1600 IU/d vitamin D3 (n = 858) or 400 IU/d vitamin D3 (n = 862) for 2 months at 24-28 weeks' gestation. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D) and fasting plasma glucose (FPG) levels from baseline, 32-36 weeks' gestation to delivery (37-41 weeks) quantified using a linear mixed model. RESULTS: After 2 months, FPG levels of the control group significantly increased by 0.22 mmol/L (from 4.6 [0.4] mmol/L to 4.8 [1.2] mmol/L, P < 0.001) at delivery, but that of the intervention group had no significant variation (from 4.6 [0.4] mmol/L to 4.7 [1.1] mmol/L; between-group difference in changes, -0.2 mmol/L, 95% CI, -0.3 to -0.08, P = 0.015). And differences in FPG variation were found in participants with the ApaI SNP CC genotype, or BsmI-CC, TaqI-AA, FokI-AA, respectively. Pregnant women with basal 25(OH)D concentrations higher than 50 nmol/L subgroup showed the greatest decline in FPG levels (between-group difference, -0.3 mmol/L; 95% CI, -0.5 to -0.1, P < 0.001). Moreover, pregnant women with GDM, multiple pregnancies or who were overweight were more likely to have FPG decline from vitamin D treatment. CONCLUSIONS: Vitamin D supplementation significantly protected glucose homeostasis in mid-late gestation, and glycemic response to vitamin D may be dependent on basal 25(OH)D status, VDR gene polymorphism or their metabolic profiles. TRIAL REGISTRATION NUMBER: ChiCTR2100051914. URL OF REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=134700.

High oil content inhibits humification in food waste composting by affecting microbial community succession and organic matter degradation.

Composting is an effective technology to realize resource utilization of food waste in rural China. However, high oil content in food waste limits composting humification. This study investigated the effects of blended plant oil addition at different proportions (0, 10, 20, and 30%) on the humification of food waste composting. Oil addition at 10%-20% enhanced lignocellulose degradation by 16.6%-20.8% and promoted humus formation. In contrast, the high proportion of oil (30%) decreased the pH, increased the electrical conductivity, and reduced the seed germination index to 64.9%. High-throughput sequencing showed that high oil inhibited the growth and reproduction of bacteria (Bacillus, Fodinicurvataceae, and Methylococcaceae) and fungi (Aspergillus), attenuated their interaction, thus, reducing the conversion of organic matter, such as lignocellulose, fat, and total sugar, to humus, consequently leading to negative impacts on composting humification. The results can guide composting parameter optimization and improve effective management of rural food waste.

Anemia in pregnancy and sleep of 6-month-old infants: A prospective cohort study.

Objective: Anemia has been reported to adversely influence sleep in infants. However, the association between anemia in pregnancy and infant sleep remains unclear. We aimed to examine the association between maternal anemia in pregnancy and sleep parameters of 6-month-old infants. Methods: We enrolled 2,410 mother-infant pairs between 2018 and 2021 in Hefei. Data on maternal hemoglobin concentration were collected at 24-28 gestational weeks from the electronic medical records of the hospitals. Nocturnal and daytime sleep duration, number of night awakenings, nocturnal wakefulness, and sleep latency of infants aged 6 months were measured using the Brief Infant Sleep Questionnaire with five items. A restricted cubic spline model was used to examine the relationship between maternal hemoglobin concentration and infant nocturnal sleep duration after adjusting for potential confounders. Results: In our study, 807 (33.5%) mothers had anemia during pregnancy. Compared to infants born to mothers without anemia, infants born to mothers with anemia in pregnancy had shorter nocturnal sleep duration [mean (SD), 560.29 (79.57) mins vs. 574.27 (75.36) mins] at the age of 6 months. Subgroup analysis showed consistent significant differences in nocturnal sleep duration between infant born to anemic and non-anemic mothers, except in case of stratification by preterm birth [mean difference (mins), 2.03 (95% CI, -20.01, -24.07)] and pre-pregnancy obesity [mean difference (mins), -0.85 (95% CI, -16.86, -15.16)]. A J-shaped nonlinear correlation curve was observed between maternal hemoglobin concentration and infant nocturnal sleep duration. Compared with mothers without daily iron supplementation, mothers who had daily iron supplementation had higher hemoglobin concentrations [mean (SD), 112.39 (11.33) g/L vs. 110.66 (10.65) g/L] at delivery and their infants had longer nocturnal sleep duration [mean (SD), 565.99 (82.46) mins vs. 553.66 (76.03) mins]. Conclusion: Anemia in pregnancy may have an adverse influence on the sleep of 6-mon-old infants, and the relationship between maternal hemoglobin concentration and nocturnal sleep duration is nonlinear.

Edible oleogels stabilized solely by stigmasterol: effect of oil type and gelator concentration.

BACKGROUND: Phytosterols are considered to be one of the most promising gelators for obtaining oleogel because of their additional health benefits and natural coexist with vegetable oils. Previous studies have confirmed that individual phytosterols are not capable of structuring vegetable oils unless they act synergistically with other components. However, based on the self-assembly properties of stigmasterol (ST) in organic solvents, we speculate that it can also structure vegetable oils as a gelator alone. RESULTS: For the first time, the present study confirmed the feasibility of using ST alone as a gelator for structuring of vegetable oils, including rapeseed oil (RSO), olive oil (OLO) and flaxseed oil (FSO). RSO had the lowest ST gelation concentration (4%, w/w), and the oil-binding capacity and firmness value of the oleogels were the highest. The rheological results showed that all the samples were gelatinous (G' > G″). The results of differential scanning calorimeter and X-ray diffraction further confirmed that the properties of RSO-based oleogels are superior to those prepared by OLO and FSO. The microscopic results also confirmed that the crystal structure of RSO oleogels was more uniform, smaller and more densely distributed. CONCLUSION: The structural properties of the oleogels were positively correlated with the ST concentration, and various analysis indicators showed that the performance of the oleogel based on RSO was better than that of OLO and FSO. In summary, the present study used ST as a gelator to successfully prepare oleogels with excellent properties, which provides a feasible reference for researchers in related fields. © 2022 Society of Chemical Industry.

Visualizing the distributions and spatiotemporal changes of metabolites in Panax notoginseng by MALDI mass spectrometry imaging.

BACKGROUND: Panax notoginseng is a highly valued medicinal herb used widely in China and many Asian countries. Its root and rhizome have long been used for the treatment of cardiovascular and hematological diseases. Imaging the spatial distributions and dynamics of metabolites in heterogeneous plant tissues is significant for characterizing the metabolic networks of Panax notoginseng, and this will also provide a highly informative approach to understand the complex molecular changes in the processing of Panax notoginseng. METHODS: Here, a high-sensitive MALDI-MS imaging method was developed and adopted to visualize the spatial distributions and spatiotemporal changes of metabolites in different botanical parts of Panax notoginseng. RESULTS: A wide spectrum of metabolites including notoginsenosides, ginsenosides, amino acids, dencichine, gluconic acid, and low-molecular-weight organic acids were imaged in Panax notoginseng rhizome and root tissues for the first time. Moreover, the spatiotemporal alterations of metabolites during the steaming of Panax notoginseng root were also characterized in this study. And, a series of metabolites such as dencichine, arginine and glutamine that changed with the steaming of Panax notoginseng were successfully screened out and imaged. CONCLUSION: These spatially-resolved metabolite data not only enhance our understanding of the Panax notoginseng metabolic networks, but also provide direct evidence that a serious of metabolic alterations occurred during the steaming of Panax notoginseng.

A new insulin-sensitive enhancer from Silene viscidula, WPTS, treats type 2 diabetes by ameliorating insulin resistance, reducing dyslipidemia, and promoting proliferation of islet ß cells.

Wacao pentacyclic triterpenoid saponins (WPTS) is a newly discovered insulin sensitivity enhancer. It is a powerful hypoglycemic compound derived from Silene viscidula, which has a hypoglycemic effect similar to that of insulin. It can rapidly reduce blood glucose levels, normalizing them within 3 days of administration. However, its mechanism of action is completely different from that of insulin. Thus, we aimed to determine the pharmacological effects and mechanism of activity of WPTS on type 2 diabetes to elucidate the main reasons for its rapid effects. The results showed that WPTS could effectively improve insulin resistance in KKAy diabetic mice. Comparative transcriptomics showed that WPTS could upregulate the expression of insulin resistance-related genes such as glucose transporter type 4 (Glut4), insulin receptor substrate 1 (Irs1), Akt, and phosphoinositide 3-kinase (PI3K), and downregulate the expression of lipid metabolism-related genes such as monoacylglycerol O-acyltransferase 1 (Moat1), lipase C (Lipc), and sphingomyelin phosphodiesterase 4 (Smpd4). The results indicated that the differentially expressed genes could regulate lipid metabolism via the PI3K/AKT metabolic pathway, and it is noteworthy that WPTS was found to upregulate Glut4 expression, decrease blood glucose levels, and attenuate insulin resistance via the PI3K/AKT pathway. Q-PCR and western blotting further validated the transcriptomics findings at the mRNA and protein levels, respectively. We believe that WPTS can achieve a rapid hypoglycemic effect by improving the lipid metabolism and insulin resistance of the diabetic KKAy mice. WPTS could be a very promising candidate drug for the treatment of diabetes and deserves further research.

Cell metabolomics to study the function mechanism of Cyperus rotundus L. on triple-negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate. According to historical records, the dry rhizomes Cyperus rotundus L. could be ground into powder and mixed with ginger juice and wine for external application for breast cancer. We studied the effect of the ethanol extract of Cyperus rotundus L. (EECR) on TNBC cells and found its' apoptosis-inducing effect with a dose-relationship. But the function mechanism of EECR on TNBC is still mysterious. Hence, the present research aimed to detect its function mechanism at the small molecule level through ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics. METHODS: The CCK-8 assay and the Annexin V-FITC/PI assay were applied to test the effect of EECR on MDA-MB-231 cells and MDA-MB 468 cells at various concentrations of 0, 200, 400, and 600 µg/ml. UPLC-Q-TOF-MS/MS based metabolomics was used between the control group and the EECR treatment groups. Multivariate statistical analysis was used to visualize the apoptosis-inducing action of EECR and filtrate significantly changed metabolites. RESULTS: The apoptosis-inducing action was confirmed and forty-nine significantly changed metabolites (VIP > 1, p < 0.05, and FC > 1.2 or FC < 0.8) were identified after the interference of EECR. The level of significant differential metabolites between control group, middle dose group, and high dose group were compared and found that which supported the apoptosis-inducing action with dose-dependence. CONCLUSION: By means of metabolism, we have detected the mechanism of EECR inducing apoptosis of TNBC cells at the level of small molecule metabolites and found that EECR impacted the energy metabolism of TNBC cells. In addition, we concluded that EECR induced apoptosis by breaking the balance between ATP-production and ATP-consumption: arresting the pathways of Carbohydrate metabolism such as Central carbon metabolism in cancer, aerobic glycolysis, and Amino sugar and nucleotide sugar metabolism, whereas accelerating the pathways of ATP-consumption including Amino Acids metabolism, Fatty acid metabolism, Riboflavin metabolism and Purine metabolism. Although further study is still needed, EECR has great potential in the clinical treatment of TNBC with fewer toxic and side effects.

A specific gut microbiota and metabolomic profiles shifts related to antidiabetic action: The similar and complementary antidiabetic properties of type 3 resistant starch from Canna edulis and metformin.

The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has drawn increasing attention, and the benefits of various treatment strategies, including nutrition, medication and physical exercise, maybe microbially-mediated. Metformin is a widely used hypoglycemic agent, while resistant starch (RS) is a novel dietary fiber that emerges as a nutritional strategy for metabolic disease. However, it remains unclear as to the potential degree and interactions among gut microbial communities, metabolic landscape, and the anti-diabetic effects of metformin and RS, especially for a novel type 3 resistant starch from Canna edulis (Ce-RS3). In the present study, T2DM rats were administered metformin or Ce-RS3, and the changes in gut microbiota and serum metabolic profiles were characterized using 16S-rRNA gene sequencing and metabolomics, respectively. After 11 weeks of treatment, Ce-RS3 exhibited similar anti-diabetic effects to those of metformin, including dramatically reducing blood glucose, ameliorating the response to insulin resistance and glucose tolerance test, and relieving the pathological damage in T2DM rats. Interestingly, the microbial and systemic metabolic dysbiosis in T2DM rats was effectively modulated by both Ce-RS3 and, to a lesser extent, metformin. The two treatments increased the gut bacterial diversity, and supported the restoration of SCFA-producing bacteria, thereby significantly increasing SCFAs levels. Both treatments simultaneously corrected 16 abnormal metabolites in the metabolism of lipids and amino acids, many of which are microbiome-related. PICRUSt analysis and correlation of SCFAs levels with metabolomics data revealed a strong association between gut microbial and host metabolic changes. Strikingly, Ce-RS3 exhibited better efficacy in increasing gut microbiota diversity with a peculiar enrichment of Prevotella genera. The gut microbial properties of Ce-RS3 were tightly associated with the T2DM-related indexes, showing the potential to alleviate diabetic phenotype dysbioses, and possibly explaining the greater efficiency in improving metabolic control. The beneficial effects of Ce-RS3 and metformin might derive from changes in gut microbiota through altering host-microbiota interactions with impact on the host metabolome. Given the complementarity of Ce-RS3 and metformin in regulation of gut microbiota and metabolites, this study also prompted us to suggest possible "Drug-Dietary fiber" combinations for managing T2DM.

The role of parathyroid hormone during pregnancy on the relationship between maternal vitamin D deficiency and fetal growth restriction: a prospective birth cohort study.

Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted ß = -49·4 g, 95 % CI -91·1, -7·8, P < 0·05; for severe VDD: adjusted ß = -79·8 g, 95 % CI -127·2, -32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted ß = -44·5 g, 95 % CI -82·6, -6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted ß = -124·7 g, 95 % CI -194·6, -54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.

Plasma metabolomics analysis of endogenous and exogenous metabolites in the rat after administration of Lonicerae Japonicae Flos.

Lonicerae Japonicae Flos (LJF) is a typical herbal medicine and is used as a functional food. LJF, which has complex chemical compounds, has various biological effects. The global metabolomics, focusing on both the endogenous and exogenous metabolites, have not yet been investigated for LJF in normal healthy rats using LC-MS. In this study, plasma metabolomics was analyzed after the administration of LJF at different time intervals, and the exogenous metabolites were identified. Partial least squares discriminant analysis showed significant differences in chemical content in the dosed rats. Cholic acid, indoleacrylic acid, indolelactic acid, hippuric acid, N-acetyl-phenylalanine, and N-acetyl-serotonin significantly accumulated in the dosed rats. Lysophosphatidylethanolamine and lysophosphatidylcholine content, including plasmalogen, increased. There were 25 components of LJF, including 15 prototypes and 10 metabolites, that were identified. The 15 prototypes included phenolic acids, flavonoids, and iridoids, and their contents decreased with an increase in the administration time. Glucuronidation and sulfation of polyphenols were found for LJF. The exogenous glucuronide and sulfate metabolites-including dihydrocoumaric acid-sulfate, dihydrocaffeic acid-sulfate, dihydroferulic acid-sulfate, apigenin-glucuronide, apigenin-glucuronide-sulfate, isorhamnetin-glucuronide-sulfate, and others-were identified with a neutral loss of 176 and 80, respectively. The metabolic differences found in the study may serve as biomarkers of LJF consumption and promote the understanding of the mechanism of action of LJF.

The treatment role of Cyperus rotundus L. to triple-negative breast cancer cells.

Cyperus rotundus L. is widely used in Traditional Chinese Medicine and studies have reported its anticancer effect, but its chemical composition and therapy mechanism remains unknown. This research aims to analyze the chemical components of the ethanol extract of Cyperus rotundus L. (EECR), detect its treatment effects on human Triple-negative breast cancer (TNBC) cells, and elucidate possible therapy mechanisms. The chemical components of EECR were detected by the Waters UPLC combined with Bruker Q-TOF mass spectrometer (UPLC-Q-TOF-MS). The phytochemical compounds were identified by comparing the mass fragmentations of each metabolite with databases such as METLIN, HMDB, and NCBI. A total of 21 compounds were identified in EECR. MDA-MB-231 and MDA-MB-468 cells were treated with various concentrations of EECR. Cell proliferation was examined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle were detected by flow cytometry. Apoptosis- and autophagy-related protein expression was detected by Western blot. EECR inhibits the proliferation of TNBC cells (MDA-MB-231 and MDA-MB-468) in a dose-dependent manner, which may be related to the arrest of cell cycle in G0/G1 phase. It induces apoptosis by promoting the expression of BAX and inhibiting the expression of BCL-2. In addition, autophagy inhibitor 3-Methyladenine (3-MA) inhibited TNBC cells pro-survival autophagy and increased the sensitivity of EECR. The present results demonstrated that EECR has potential effects on inhibits the proliferation and induction apoptosis in TNBC.

Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus.

Body weight is related to fat mass, which is associated with obesity. Our study explored the effect of fat-1 gene on body weight in fat-1 transgenic mice. In present study, we observed that the weight/length ratio of fat-1 transgenic mice was lower than that of wild-type mice. The serum levels of triglycerides (TG), cholesterol (CT), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and blood glucose (BG) in fat-1 transgenic mice were all decreased. The weights of peri-bowels fat, perirenal fat and peri-testicular fat in fat-1 transgenic mice were reduced. We hypothesized that increase of n-3 PUFAs might alter the expression of hypothalamic neuropeptide genes and lead to loss of body weight in fat-1 transgenic mice. Therefore, we measured mRNA levels of appetite neuropeptides, Neuropeptide Y (NPY), Agouti-related peptides (AgRP), Proopiomelanocortin (POMC), Cocaine and amphetamine regulated transcript (CART), ghrelin and nesfatin-1 in hypothalamus by real-time PCR. Compared with wild-type mice, the mRNA levels of CART, POMC and ghrelin were higher, while the mRNA levels of NPY, AgRP and nesfatin-1 were lower in fat-1 transgenic mice. The results indicate that fat-1 gene or n-3 PUFAs participates in regulation of body weight, and the mechanism of this phenomenon involves the expression of appetite neuropeptides and lipoproteins in fat-1 transgenic mice.

Calcium plus vitamin D3 supplementation facilitated fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial.

BACKGROUND: Recent evidence suggests that higher calcium and/or vitamin D intake may be associated with lower body weight and better metabolic health. Due to contradictory findings from intervention trials, we investigated the effect of calcium plus vitamin D3 (calcium+D) supplementation on anthropometric and metabolic profiles during energy restriction in healthy, overweight and obese adults with very-low calcium consumption. METHODS: Fifty-three subjects were randomly assigned in an open-label, randomized controlled trial to receive either an energy-restricted diet (-500 kcal/d) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks. Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight, BMI, body composition, waist circumference, and blood pressures, as well as in plasma TG, TC, HDL, LDL, glucose and insulin concentrations. RESULTS: Eighty-one percent of participants completed the trial (85% from the calcium + D group; 78% from the control group). A significantly greater decrease in fat mass loss was observed in the calcium + D group (-2.8±1.3 vs.-1.8±1.3 kg; P=0.02) than in the control group, although there was no significant difference in body weight change (P>0.05) between groups. The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area (P<0.05 for both). No significant difference was detected for changes in metabolic variables (P>0.05). CONCLUSION: Calcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01447433, http://clinicaltrials.gov/).