Perinatal Plasma Carotenoids and Vitamin E Concentrations with Glycemia and Insulin Resistance in Women during and after Pregnancy.

We examined the associations of perinatal plasma carotenoids and E vitamers concentrations with glycemia, insulin resistance, and gestational and type 2 diabetes mellitus during pregnancy and post-pregnancy in GUSTO women. Plasma carotenoid and E vitamer concentrations were measured at delivery, and principal component analysis was used to derive the patterns of their concentrations. Fasting and 2 h glucose levels and fasting insulin were measured at 26-28 weeks gestation and 4-6 years post-pregnancy, with the derivation of homeostatic model assessment for insulin resistance (HOMA-IR). In 678 women, two carotenoid patterns (CP1: α- and ß-carotene and lutein; CP2: zeaxanthin, lycopene, and ß-cryptoxanthin) and one E vitamer pattern (VE: γ-, δ-, and α-tocopherols) were derived. A higher CP1 score (1-SD) was associated with lower gestational fasting glucose (ß (95%CI): -0.06 (-0.10, -0.02) mmol/L) and lower gestational (-0.17 (-0.82, 0.01) mmol/L, p = 0.06) and post-pregnancy HOMA-IR (-0.11 (-0.15, -0.08) mmol/L). A higher VE score (1 SD) was associated with higher gestational and post-pregnancy fasting and 2 h glucose (gestational: 0.05 (0.01, 0.08) and 0.08 (0.01, 0.16); post-pregnancy: 0.19 (0.07, 0.31) and 0.24 (0.06, 0.42) mmol/L). Higher α- and ß-carotene and lutein may be beneficial for gestational fasting glycemia, but higher vitamin E may increase gestational and post-pregnancy glycemia, although these findings require confirmation in cohorts with prospective longitudinal measurements of these vitamins.

Association between Vitamin A and E Forms and Prostate Cancer Risk in the Singapore Prostate Cancer Study.

PURPOSE: This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify potential effect modifiers. METHODS: Utilizing data from the Singapore Prostate Cancer Study, a hospital-based case-control study, we measured the serum concentrations of 15 different forms of vitamins A and E in 156 prostate cancer patients and 118 control subjects, using a high-performance liquid chromatography technique. These forms included retinol, lutein, zeaxanthin, α-cryptoxanthin, ß-cryptoxanthin, α-carotene, ß-carotene, lycopene, ubiquinone, δ-tocopherol, γ-tocopherol, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol. The odds ratio and 95% confidence interval for associations between vitamin A and E and prostate cancer risk were estimated using logistic regression models after adjustment for potential confounders. The analyses were further stratified by smoking and alcohol consumption status. The mixture effect of micronutrient groups was evaluated using weighted quantile sum regression. RESULTS: Higher concentrations of retinol, lutein, α-carotene, ß-carotene, ubiquinone, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol were significantly and positively associated with overall prostate cancer risk. Among ever-smokers, associations were stronger for lutein, ß-cryptoxanthin and ß-carotene compared with never-smokers. Among regular alcohol drinkers, associations were stronger for lutein, ß-cryptoxanthin, ubiquinone, γ-tocotrienol and α-tocotrienol compared with non-regular alcohol drinkers. Retinol and α-tocotrienol contributed most to the group indices 'vitamin A and provitamin A carotenoids' and 'vitamin E', respectively. CONCLUSIONS: Several serum vitamin A and E forms were associated with prostate cancer risk, with significant effect modification by smoking and alcohol consumption status. Our findings shed light on prostate cancer etiology.

Safety, Tolerability, and Pharmacokinetics of ß-Cryptoxanthin Supplementation in Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: ß-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation. METHODS: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral ß-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of ß-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated. RESULTS: ß-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma ß-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) (p < 0.03), and placebo (0.4 ± 0.1 µmol/L) (p < 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, ß-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition. CONCLUSIONS: Oral ß-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of ß-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women.

Dydrogesterone disrupts lipid metabolism in zebrafish brain: A study based on metabolomics and Fourier transform infrared spectroscopy.

Brain is a potential target for neuroprogestogens and/or peripheral progestogens. Previous studies reported that expression of genes about steroidogenesis, reproduction, cell cycle, and circadian rhythm in zebrafish brain could be affected by progestogens. However, there are limited information from metabolites or biomacromolecules aspects, leaving an enormous gap in understanding toxic effects of progestogens on fish brain. In this study, we exposed zebrafish embryos to 2.8, 27.6, and 289.8 ng/L dydrogesterone (DDG, a synthetic progestogen) until sexual maturity (140 days). LC-MS and GC-MS based untargeted metabolomics and Fourier-transform infrared (FTIR) spectroscopy were then performed to investigate the metabolic profiles and macromolecular changes of brain of these zebrafish. The results from multivariate statistical analysis of metabolite features showed a clear separation between different treatment groups of both female and male zebrafish brains. DDG exposure increased the levels of cholesterol, saturated fatty acids, and nucleoside monophosphates, but decreased the contents of polyunsaturated fatty acids (PUFAs), lysophosphatides, and nucleosides in dose-dependent manner. FTIR results indicated that DDG exposure led to accumulation of saturated lipids, reduction of nucleic acids and carbohydrates, and alteration of protein secondary structures. The findings from this study demonstrated that DDG could affect contents of metabolites and biomacromolecules of zebrafish brain, which may finally lead to brain dysfunctions.

Perinatal plasma carotenoid and vitamin E concentrations with maternal blood pressure during and after pregnancy.

BACKGROUND AND AIMS: Few studies examined the influence of carotenoids and vitamin E on blood pressure or hypertension during and after pregnancy. We related perinatal plasma concentrations of carotenoids and vitamin E (in individual forms and in combination) to blood pressure and hypertension at late pregnancy and 4 years post-pregnancy. METHODS AND RESULTS: In 684 women of the Growing Up in Singapore Towards Healthy Outcomes cohort, we quantified plasma carotenoids and vitamin E concentrations at delivery. Systolic blood pressure and diastolic blood pressure (SBP and DBP) around 37-39 weeks' gestation were extracted from obstetric records and measured at 4 years post-pregnancy. Principal component analysis derived patterns of carotenoids (CP) and vitamin E. Associations were examined using linear or logistic regressions adjusting for confounders. Two carotenoids (CP1: α-carotene, ß-carotene, and lutein; CP2: zeaxanthin, lycopene, and ß-cryptoxanthin) and one vitamin E (γ-, δ-, and α-tocopherols) patterns were derived. CP1 (1SD score increment) was associated with lower SBP and DBP [ß (95% CI): -2.36 (-3.47, -1.26) and -1.37 (-2.21, -0.53) mmHg] at late pregnancy> and 4 years post-pregnancy [-1.45 (-2.72, -0.18) and -0.99 (-1.98, -0.01) mmHg]. Higher ß-cryptoxanthin concentrations were associated with lower SBP and DBP [-1.50 (-2.49, -0.51) and -1.20 (-1.95, -0.46) mmHg] at late pregnancy. Individual vitamin E and their pattern were not associated with blood pressure or hypertension. CONCLUSION: Higher perinatal α-carotene, ß-carotene, and lutein concentrations are associated with lower blood pressure in women at late pregnancy and post-pregnancy. Foods rich in these carotenoids, such as red-, orange-, and dark-green-colored vegetables, might be beneficial for blood pressure during and after pregnancy.

A field study on using soybean waste-derived superabsorbent hydrogel to enhance growth of vegetables.

Food security is critical and has become a global concern with many of our basic food crops growing in areas with high drought risk. To improve soil water holding capacity, hydrogels are a promising solution. However, the current ones are mostly derived from petroleum products and are environmental unsustainable. In this study, the main objective is to determine if bio-based hydrogel can help in the growth of leafy vegetables while minimizing water use under field conditions. To achieve this, we developed an okara-derived hydrogel (Ok-PAA; OP) from by-products of bean curd and soybean milk production. We incorporated OP into soil and assessed the growth performance of leafy vegetables. We observed that vegetables grown with 0.2% (w/v) OP in soil with a watering frequency of 7 times per week resulted in >60 % and 35 % yield increase for the common Asian leafy vegetables, choy sum (CS) and pak choi (PC), respectively, as compared to without hydrogel supplementation. Both vegetables produced larger leaf areas (20-40 % increment) in the presence of the hydrogel as compared to those without. In addition, with OP amendment, the irrigation water use efficiency improved >60 % and 30 % for CS and PC, respectively. It is estimated that with the use of the hydrogel, a reduction in watering frequency from 21 times to 7 times per week could be achieved, and based on a per hectare estimation, this would result in 196,000 L of water saving per crop cycle. Statistical analysis and modelling further confirmed vegetables grown with 0.2 % (w/v) OP and with a watering frequency of 7 times per week showed the best growth performance and water use efficiency. Such a waste-to-resource approach offers a plant-based soil supplement for crop growers, contributes to waste valorization, and enhances the growth of plants especially under water-limited conditions.

Assessment of human exposure to benzophenone-type UV filters: A review.

To avoid the harmful effects of UV radiation, benzophenone-type UV filters (BPs) are widely used in personal care products and other synthetic products. Biomonitoring studies have shown the presence of BPs in various human biological samples, raising health concerns. However, there is a paucity of data on the global human exposure to this group of contaminants. In this study, we compiled data on the body burden of BPs along with the possible exposure routes and biotransformation pathways. BPs can easily penetrate the skin barrier and thus, they can be absorbed through the skin. In the human body, BPs can undergo Phase I (mainly demethylation and hydroxylation) and Phase II (mainly glucuronidation and sulfation) biotransformations. From a total of 158 studies, most of the studies are related to urine (concentration up to 92.7 mg L-1), followed by those reported in blood (up to 0.9 mg L-1) and milk (up to 0.8 mg L-1). Among BPs, benzophenone-1 and benzophenone-3 are the most commonly detected congeners. The body burden of BPs is associated with various factors, including the country of residence, lifestyle, income, education level, and ethnicity. The presence of BPs in maternal urine (up to 1.1 mg L-1), placenta (up to 9.8 ng g-1), and amniotic fluid (up to 15.7 µg L-1) suggests potential risks of prenatal exposure. In addition, transplacental transfer of BPs is possible, as demonstrated by their presence in maternal serum and cord serum. The possible association of BPs exposure and health effects was discussed. Future human biomonitoring studies and studies on the potential health effects are warranted. Overall, this review provides a summary of the global human exposure to BPs and can serve as supporting evidence to guide usage in order to protect humans from being exposed to BPs.

Annexin-A1 deficiency attenuates stress-induced tumor growth via fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis.

Background: High emotional or psychophysical stress levels have been correlated with an increased risk and progression of various diseases. How stress impacts the gut microbiota to influence metabolism and subsequent cancer progression is unclear. Methods: Feces and serum samples from BALB/c ANXA1+/+ and ANXA1-/- mice with or without chronic restraint stress were used for 16S rRNA gene sequencing and GC-MS metabolomics analysis to investigate the effect of stress on microbiome and metabolomics during stress and breast tumorigenesis. Breast tumors samples from stressed and non-stressed mice were used to perform Whole-Genome Bisulfite Sequencing (WGBS) and RNAseq analysis to construct the potential network from candidate hub genes. Finally, machine learning and integrated analysis were used to map the axis from chronic restraint stress to breast cancer development. Results: We report that chronic stress promotes breast tumor growth via a stress-microbiome-metabolite-epigenetic-oncology (SMMEO) axis. Chronic restraint stress in mice alters the microbiome composition and fatty acids metabolism and induces an epigenetic signature in tumors xenografted after stress. Subsequent machine learning and systemic modeling analyses identified a significant correlation among microbiome composition, metabolites, and differentially methylated regions in stressed tumors. Moreover, silencing Annexin-A1 inhibits the changes in the gut microbiome and fatty acid metabolism after stress as well as basal and stress-induced tumor growth. Conclusions: These data support a physiological axis linking the microbiome and metabolites to cancer epigenetics and inflammation. The identification of this axis could propel the next phase of experimental discovery in further understanding the underlying molecular mechanism of tumorigenesis caused by physiological stress.

Untargeted Metabolomic Analysis of Nonvolatile and Volatile Glucosinolates in Brassicaceae.

Glucosinolates (GLSs) are a group of plant secondary metabolites mainly found in Cruciferous plants. The main hydrolysis products of GLSs, isothiocyanates (ITCs), are the bioactive metabolites that have shown plant defense and human cancer prevention properties. Untargeted metabolomic analysis of plant metabolites can uncover the profiles of these bioactive phytochemicals in specific plants and discover potential human health promoting products. We have developed an integrated metabolomic analysis method for plant samples, with specific focus on nonvolatile GLSs and volatile ITCs. In this chapter, we describe in detail the protocols, including metabolite extraction, high resolution LC-MS and GC-MS analysis, and data processing. The method is readily applicable to untargeted analysis of other nonvolatile and volatile metabolites in plants.

PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation.

Cancer cells adopt metabolic reprogramming to promote cell survival under metabolic stress. A key regulator of cell metabolism is AMP-activated protein kinase (AMPK) which promotes catabolism while suppresses anabolism. However, the underlying mechanism of AMPK in handling metabolic stress in cancer remains to be fully understood. In this study, by performing a proteomics screening of AMPK-interacting proteins in non-small-cell lung cancer (NSCLC) cells, we discovered the platelet isoform of phosphofructokinase 1 (PFKP), a rate-limiting enzyme in glycolysis. Moreover, PFKP was found to be highly expressed in NSCLC patients associated with poor survival. We demonstrated that the interaction of PFKP and AMPK was greatly enhanced upon glucose starvation, a process regulated by PFKP-associated metabolites. Notably, the PFKP-AMPK interaction promoted mitochondrial recruitment of AMPK which subsequently phosphorylated acetyl-CoA carboxylase 2 (ACC2) to enhance long-chain fatty acid oxidation, a process helping maintenance of the energy and redox homeostasis and eventually promoting cancer cell survival under glucose starvation. Collectively, we revealed a critical non-glycolysis-related function of PFKP in regulating long-chain fatty acid oxidation via AMPK to alleviate glucose starvation-induced metabolic stress in NSCLC cells.

An optimized CaO2-functionalized alginate bead for simultaneous and efficient removal of phosphorous and harmful cyanobacteria.

Simultaneous removal of phosphorus (P) and algae is important to mitigate eutrophication, however, it is rather challenging in remediation of harmful algal blooms (HABs)-contaminated water. In this study, a wet alginate bead functionalized by CaO2 particle formed layer by layer was prepared with an in-situ method and optimized to remove phosphorous and inhibit algae growth. The stable H2O2 release with a concentration level of 0.06 mM was observed for a period of 26 d. The content of peroxy groups (-O-O-) in the optimal bead was 0.44 mmol·g-1 through permanganate-based titration study. For solution with an initial phosphorous concentration of 10 mg·L-1, the removal was around 97% in pH 3.0-10.0. XRD, SEM, and XPS studies and kinetic modelings showed that removal of phosphorus was mainly due to formation of insoluble Ca-P compounds in the bead. The CaO2-functionalized bead inhibited algae growth with an effect lasting over 170 d, which was much better than liquid H2O2 and Ca(OH)2 bead; the phosphorous removal with an efficiency of about 70% was simultaneously obtained. Furthermore, the bead demonstrated to be effective in removing algae in the realistic water from a reservoir. In summary, this study shows that the CaO2-functionalized material is promising for simultaneous removal of phosphorous and management of HABs.

Microcystis aeruginosa removal by peroxides of hydrogen peroxide, peroxymonosulfate and peroxydisulfate without additional activators.

Harmful algal bloom (HAB) is one of the most globally severe challenges in ecological system and water safety. Hydrogen peroxide has been commonly used in the management/treatment. Solid oxidants (e.g., peroxymonosulfate (PMS) and peroxydisulfate (PDS)) may outperform liquid H2O2 due to ease in transportation, handling, and applications. However, the information on applications of PMS and PDS in algae treatment is limited. In this study, the two solid peroxides and H2O2 were investigated for the removal of the blue-green algae of Microcystis aeruginosa. H2O2 and PMS effectively removed algae in 2 d at pH 5.0, 7.0 and 9.0, while PDS was only effective at pH 5.0. The change in pH and the release of dissolved organic carbon were insignificant at 0.2 mM H2O2 and PMS. The PMS could degrade microcystin-LR and phycobiliproteins. The studies of phycobiliproteins degradation and scanning electron microscopy indicated that PMS might cause the cell inactivation mainly by damaging the chemical components in algae cell wall and membrane while H2O2 might mainly enter the cell to form oxidation pressure to kill algae. The scavenger experiments showed that radicals were not crucial in H2O2 and PDS applications. Similarly, the algae removal by PMS was obtained mainly by non-radical pathways; about 77% was direct PMS oxidation and no more than 3% was singlet oxygen-mediated process, while radical pathways of sulfate radical and hydroxyl radical accounted for 18% and 2%, respectively. For the realistic algae-contaminated natural water, the PMS effectively lasted for 60 d, while the H2O2 lasted for 12 d. This research work demonstrates that the PMS is promising in control of HAB. The findings can provide some useful design and application parameters of PMS technology for better management/treatment of algae-contaminated water.

Nutritional metabolites in Brassica rapa subsp. chinensis var. parachinensis (choy sum) at three different growth stages: Microgreen, seedling and adult plant.

Choy sum is a commonly consumed Asian green leafy brassica vegetable. A comprehensive spectrum of nutritional important metabolites, including amino acids, plant sugars, essential minerals, vitamins (A, B9, E, and K1) and glucosinolates were systematically quantified using LC-QQQ-MS, GC-QQQ-MS and ICP-MS. Significant metabolic profile shifts were observed during the three major developmental stages (microgreen, seedling and adult) studied. Primary metabolites, especially essential amino acids decreased while most plant sugars increased from microgreens to seedlings. Carotenoids, such as violaxanthin, neoxanthin, together with vitamin K1 were higher in the seedlings whereas CHO-folate vitamers and ß-cryptoxanthin were much lower in adult plants. Most essential minerals were concentrated in the microgreens, while sodium increased in adult plants. Aliphatic glucosinolates in microgreens were converted to indolic glucosinolates in the seedlings and further to aromatic glucosinolates in the adults. Overall findings reveal that most of the nutritional metabolites were concentrated either in the microgreens or seedlings.

Peat-forest burning smoke in Maritime Continent: Impacts on receptor PM2.5 and implications at emission sources.

This study characterizes the impacts of transported peat-forest (PF) burning smoke on an urban environment and evaluates associated source burning conditions based on carbon properties of PM2.5 at the receptor site. We developed and validated a three-step classification that enables systematic and more rapid identification of PF smoke impacts on a tropical urban environment with diverse emissions and complex atmospheric processes. This approach was used to characterize over 300 daily PM2.5 data collected during 2011-2013, 2015 and 2019 in Singapore. A levoglucosan concentration of ≥0.1 µg/m3 criterion indicates dominant impacts of transported PF smoke on urban fine aerosols. This approach can be used in other ambient environments for practical and location-dependent applications. Organic carbon (OC) concentrations (as OC indicator) can be an alternate to levoglucosan for assessing smoke impacts on urban environments. Applying the OC concentration indicator identifies smoke impacts on ∼80% of daily samples in 2019 and shows an accuracy of 51-86% for hourly evaluation. Following the systematic identification of urban PM2.5 predominantly affected by PF smoke in 2011-2013, 2015 and 2019, we assessed the concentration ratio of char-EC/soot-EC as an indicator of smoldering- or flaming-dominated burning emissions. When under the influence of transported PF smoke, the mean concentration ratio of char-EC to soot-EC in urban PM2.5 decreased by >70% from 8.2 in 2011 to 2.3 in 2015 but increased to 3.8 in 2019 (p < 0.05). The reversed trend with a 65% increase from 2015 to 2019 shows stronger smoldering relative to flaming, indicating a higher level of soil moisture at smoke origins, possibly associated with rewetting and revegetating peatlands since 2016.

Transcriptomic analysis identifies dysregulated genes and functional networks in human small airway epithelial cells exposed to ambient PM2.5.

Cellular models exhibiting human physiological features of pseudostratified columnar epithelia, provide a more realistic approach for elucidating detailed mechanisms underlying PM2.5-induced pulmonary toxicity. In this study, we characterized the barrier and mucociliary functions of differentiated human small airway epithelial cells (SAECs), cultured at the air-liquid interface (ALI). Due to the presence of mucociliary protection, particle internalization was reduced, with a concomitant decrease in cytotoxicity in differentiated S-ALI cells, as compared to conventional submerged SAEC cultures. After 24-hour exposure to PM2.5 surrogates, 117 up-regulated genes and 156 down-regulated genes were detected in S-ALI cells, through transcriptomic analysis using the Affymetrix Clariom™ S Human Array. Transcription-level changes in >60 signaling pathways, were revealed by functional annotation of the 273 differentially expressed genes, using the PANTHER Gene List Analysis. These pathways are involved in multiple cellular processes, that include inflammation and apoptosis. Exposure to urban PM2.5 led to complex responses in airway epithelia, including a net induction of downstream pro-inflammatory and pro-apoptotic responses. Collectively, this study highlights the importance of using the more advanced ALI model rather than the undifferentiated submerged model, to avoid over-assessment of inhaled particle toxicity in human. The results of our study also suggest that reduction of ambient PM2.5 concentrations would have a protective effect on respiratory health in humans.

Higher maternal plasma ß-cryptoxanthin concentration is associated with better cognitive and motor development in offspring at 2 years of age.

PURPOSE: Current literature on the roles of α-, ß-carotene and ß-cryptoxanthin in neurocognitive function has largely focused on preventing cognitive decline in older people, and less on neuro-development in children. We examined the relations of maternal plasma carotenoids concentrations with offspring cognitive development up to age 4.5 years in the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. METHODS: Maternal plasma α-, ß-carotene and ß-cryptoxanthin concentrations at delivery were determined by ultra-performance liquid chromatography. Children's cognition was assessed at ages 2 (Bayley Scales of Infant and Toddler Development) and 4.5 (Kaufman Brief Intelligence Test) years. Associations were examined in 419 mother-offspring pairs using linear regressions adjusting for key confounders. RESULTS: Median and interquartile range of maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032, 0.081), ß-carotene 0.189 (0.134, 0.286), and ß-cryptoxanthin 0.199 (0.123, 0.304). In 2 years old children, higher maternal carotenoids [per standard deviation (SD) log-concentration] were positively associated with neurocognitive functions: ß-cryptoxanthin with higher scores in cognitive [ß = 0.18, (0.08, 0.28) SD], receptive language [ß = 0.17 (0.07, 0.27) SD], fine motor [ß = 0.16 (0.05, 0.26) SD], and gross motor [ß = 0.16 (0.06, 0.27) SD] scales; ß-carotene with higher cognitive score [ß = 0.17 (0.05, 0.29) SD]. No significant associations were observed with neurocognitive functions at age 4.5 years. CONCLUSION: Our study provides novel data suggesting a potential role of prenatal carotenoids, particularly ß-cryptoxanthin, on early offspring cognitive and motor development. Whether the prenatal influences sustain beyond early childhood requires further investigation in longer term studies.

Skin carotenoids status as a potential surrogate marker for cardiovascular disease risk determination in middle-aged and older adults.

BACKGROUND AND AIMS: Upon consumption, carotenoids, which may attenuate cardiovascular disease (CVD) risk, diffuse from the blood and accumulate in the skin. This study aimed to assess the associations between dietary, plasma, and skin carotenoids with CVD risk indicators and to examine the mediational role of plasma carotenoids in the relationship between skin carotenoids status (SCS) and CVD risk. METHODS AND RESULTS: Dietary, plasma, and skin carotenoids were assessed in a cross-sectional study from a community in Singapore (n = 103) aged 50 to 75 y. Multiple linear regression and binary logistics regression models were used to examine the associations between the carotenoids status with classical CVD risk factors and composite CVD risk indicators. After controlling for covariates, SCS and plasma carotenoids were inversely associated with systolic blood pressure (skin: P < 0.001; plasma: P < 0.05) and diastolic blood pressure (skin: P < 0.001; plasma: P < 0.005). Additionally, each increment of 1000 in SCS was associated with an odds ratio of 0.924 (P < 0.01) for metabolic syndrome diagnosis and 0.945 (P < 0.05) for moderate to high CVD risk classification. Associations between SCS and composite CVD risk indicators were null when adjusted for the corresponding plasma carotenoids, indicating complete mediation. Dietary carotenoids, however, showed no relationship with the CVD risk indicators. CONCLUSION: Carotenoids bioavailability may be important for cardiovascular protection. SCS, driven by the corresponding plasma carotenoids, could be a potential noninvasive surrogate marker for CVD risk determination in middle-aged and older adults. CLINICAL TRIAL REGISTRATION: NCT03554954, https://clinicaltrials.gov/. TRIAL REGISTRATION DATE: 13 June 2018.

Effect of plasma polyunsaturated fatty acid levels on leukocyte telomere lengths in the Singaporean Chinese population.

BACKGROUND: Shorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging. Increased dietary intake of marine n-3 PUFA is associated with reduced telomere attrition. However, the effect of plasma PUFA on leukocyte telomere length (LTL) and its interaction with genetic variants are not well established. METHODS: A nested coronary artery disease (CAD) case-control study comprising 711 cases and 638 controls was conducted within the Singapore Chinese Health Study (SCHS). Samples genotyped with the Illumina ZhongHua-8 array. Plasma n-3 and n-6 PUFA were quantified using mass spectrometry (MS). LTL was measured with quantitative PCR method. Linear regression was used to test the association between PUFA and LTL. The interaction between plasma PUFAs and genetic variants was assessed by introducing an additional term (PUFA×genetic variant) in the regression model. Analysis was carried out in cases and controls separately and subsequently meta-analyzed using the inverse-variance weighted method. We further assessed the association of PUFA and LTL with CAD risk by Cox Proportional-Hazards model and whether the effect of PUFA on CAD was mediated through LTL by using structural equation modeling. RESULTS: Higher n6:n3 ratio was significantly associated with shorter LTL (p = 0.018) and increased CAD risk (p = 0.005). These associations were mainly driven by elevated plasma total n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (p < 0.05). There was a statistically significant interaction for an intergenic single nucleotide polymorphism (SNP) rs529143 with plasma total n-3 PUFA and DHA on LTL beyond the genome-wide threshold (p < 5 ×  10- 8). Mediation analysis showed that PUFA and LTL affected CAD risk independently. CONCLUSIONS: Higher plasma n6:n3 PUFA ratio, and lower EPA and DHA n-3 PUFAs were associated with shorter LTL and increased CAD risk in this Chinese population. Furthermore, genetic variants may modify the effect of PUFAs on LTL. PUFA and LTL had independent effect on CAD risk in our study population.

An Integrated Metabolomics Study of Glucosinolate Metabolism in Different Brassicaceae Genera.

Glucosinolates are a group of plant secondary metabolites that can be hydrolyzed into a variety of breakdown products such as isothiocyanates, thiocyanates, and nitriles. These breakdown products can facilitate plant defense and function as attractants to natural enemies of insect pests. As part of the diet, some of these compounds have shown cancer-preventing activities, and the levels of these metabolites in the edible parts of the plants are of interest. In this study, we systematically examined variations in glucosinolates, their precursors, and their breakdown products in 12 commonly consumed vegetables of the Brassicaceae family with gas chromatography-quadrupole time-of-flight mass spectrometer (GC-Q-TOF/MS), liquid chromatography-quadrupole time-of-flight mass spectrometer (LC-Q-TOF/MS), and liquid chromatography-triple quadrupole mass spectrometer (LC-QQQ/MS), using both untargeted and targeted approaches. The findings were integrated with data from literature to provide a comprehensive map of pathways for biosynthesis of glucosinolates and isothiocyanates. The levels of precursor glucosinolates are found to correlate well with their downstream breakdown products. Further, the types and abundances of glucosinolates among different genera are significantly different, and these data allow the classification of plants based on morphological taxonomy. Further validation on three genera, which are grown underground, in damp soil, and above ground, suggests that each genus has its specific biosynthetic pathways and that there are variations in some common glucosinolate biosynthesis pathways. Our methods and results provide a good starting point for further investigations into specific aspects of glucosinolate metabolism in the Brassica vegetables.

Urban PM2.5 reduces angiogenic ability of endothelial cells in an alveolar-capillary co-culture lung model.

Adverse health effects arising from exposure to fine particulates have become a major concern. Angiogenesis is a vital physiological process for the growth and development of cells and structures in the human body, whereby excessive or insufficient vessel growth could contribute to pathogenesis of diseases. We therefore evaluated indirect effects of carbon black (CB) and inhalable airborne particles on the angiogenic ability of unexposed Human Umbilical Vein Endothelial Cells (HUVECs) by co-culturing HUVECs with pre-exposed Small Airway Epithelial Cells (SAECs). As endothelial cells are major components of blood vessels and potential targets of fine particles, we investigated if lung epithelial cells exposed to ambient PM2.5 surrogates could induce bystander effects on neighboring unexposed endothelial cells in an alveolar-capillary co-culture lung model. Epithelial exposure to CB at a non-toxic dose of 25 µg/mL reduced endothelial tube formation and cell adhesion in co-cultured HUVECs, and decreased expression of angiogenic genes in SAECs. Similarly, exposure of differentiated SAECs to PM2.5 surrogates reduced cell reproductive ability, adhesion and tube formation of neighboring HUVECs. This indicates epithelial exposure to CB and urban PM2.5 surrogates both compromised the angiogenic ability of endothelial cells through bystander effects, thereby potentially perturbing the ventilation-perfusion ratio and affecting lung function.