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1.
Cardiovasc Diabetol ; 18(1): 151, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722714

RESUMO

BACKGROUND: The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk. METHODS: Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography-tandem mass spectrometry, at baseline and after 1-year of intervention. RESULTS: In weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06-1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05-1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites. CONCLUSIONS: Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003.

2.
Int Urol Nephrol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667689

RESUMO

BACKGROUND: The relationship between the endothelial glycocalyx constituents and the early failure of autologous arteriovenous fistulas (AVFs) in ESRD patients is still unknown. METHODS: In this prospective cohort study, 181 ESRD patients (the mean age was 53.3 ± 11.8 years, 66.3% of them were males) received forearm AVFs surgery were consecutively enrolled with a median follow-up time of 10 months. The early AVF failure was defined as a fistula that never developed adequately for dialysis use or that failed within the first 3 months of use. The serum levels of glycocalyx constituents including glypicans-1 (GPC-1), syndecans-1 (SDC-1), and hyaluronan (HA), and the indicator of endothelial activation reflected by E-selectin (ES) were determined by ELISAs. RESULTS: The primary patencies of AVFs were 98.3%, 96.7%, 91.7%, and 89.5% at 3, 6, 12, and 18 months, respectively. The ROC curve was plotted and demonstrated that HA, not GPC-1, SDC-1 or ES, can diagnose the AVF failure, with the cut-off value of 6.37 ng/ml, the sensitivity of 87.5%, the specificity of 46.9%, and the Youden index of 0.34, respectively. The Kaplan-Meier survival analysis demonstrated that patients with HA < 6.37 ng/mL had better patency of AVFs than patients with HA ≥ 6.37 ng/mL (log-rank test, p = 0.008). In the Cox proportional hazards analysis, after adjusting for confounders, HA (≥ 6.37 ng/mL vs. < 6.37 ng/mL) was associated with the early AVFs failure, with the OR of 5.88 (1.21-28.60). CONCLUSIONS: This study demonstrated that HA can predict the early failure of forearm AVFs, when its serum level is more than 6.37 ng/mL.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31669095

RESUMO

BACKGROUND: Clinical and epidemiological studies have shown that obesity is associated with asthma and that these associations differ by asthma subtypes. Little is known about the shared genetic components between obesity and asthma. OBJECTIVE: To identify shared genetic associations between obesity-related traits and asthma subtypes in adults. METHODS: A cross-trait genome-wide association study (GWAS) was performed using 457,822 individuals of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma via GWAS was sought using results from obese vs. lean mouse RNA-seq and RT-PCR experiments. RESULTS: We found a substantial positive genetic correlation between BMI and later-onset asthma defined by asthma age of onset at 16 years of age or older (Rg =0.25, P=9.56×10-22). Mendelian Randomization analysis provided strong evidence in support of BMI causally increasing the risk of asthma. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and GTEx tissue eQTLs, shared immune- and cell differentiation-related pathways between obesity and asthma. Finally, RNA-seq data from lungs of obese versus control mice found that two genes (ACOXL and MYL6) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by RT-PCR in an independent set of mice. CONCLUSIONS: Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma, and identifying molecular pathways that may underlie both obesity and asthma.

4.
Ther Apher Dial ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705787

RESUMO

Failed autologous arteriovenous fistula (AVF) is a major issue in the creation of functional hemodialysis vascular access. To date, the relationship between D-dimer and AVF failure is still uncertain. So, we conducted a retrospective cohort study to explore the patency rate of forearm AVFs and to clarify whether plasma D-dimer level can predict the failure of AVFs. In this study, 290 ESRD patients (the mean age 54.1 ± 14.6 years, 63.8% of them were males) receiving forearm AVFs surgery were consecutively enrolled with a median follow-up time of 34 months. Primary patency rates and risk factors associated with AVFs failure were explored by the Kaplan-Meier method or Cox proportional hazards model. Patients were divided into 2 groups based on the median level of D-dimer (group 1<1.1mg/L and group 2≥1.1mg/L). The Kaplan-Meier survival analysis demonstrated that the patency of AVF in group 1 was similar in group 2, which were 92.4% vs. 88.9%, 84.8% vs. 84.0%, 80.0% vs. 79.2%, 76.7% vs. 78.5%, and 76.7% vs. 78.5% at 12, 24, 36, 48 and 60months (Log-rank test, P=0.8), respectively. In the crude analysis, D-dimer (per 1mg/L increase) was independently associated with AVFs failure, with OR of 1.08 (95% CI, 1.02-1.15). However, after adjusting for potential confounders, the D-dimer (per 1mg/L increase) was not associated with the AVFs failure (OR=1.06, 95% CI=0.99-1.13). This study did not find that the plasma D-dimer level can predict the failure of forearm AVFs. This article is protected by copyright. All rights reserved.

5.
Ther Apher Dial ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574579

RESUMO

High body mass index (BMI) is the most common parameter to assess excess adiposity, and has been linked to glomerular hyperfiltration (GH). However, BMI may be misleading in the estimation of body fat content due to its inability to discriminate between body fat and lean mass. In recent years, the convenient biological impedance analysis has made prediction of certain diseases somewhat feasible and accessible using body composition (BC). Accordingly, we conducted a cross-sectional study to explore the association between BC and GH among Chinese adult population. A total of 6902 adults (aged 38.6 ± 8.3 years, 70.1% males) who consecutively visited the Health Checkup Clinic were enrolled. BC including fat mass and lean body mass (LBM) was evaluated by biological impedance analysis. The upper quartile of eGFR which exceeded 117.3 mL/min/1.73 m2 was defined as GH, in comparison with the lower three quartiles (control group). As a categorical outcome, GH subjects had higher fat/LBM than the control group, which was 34.7 ± 10.9 (%) vs. 34.0 ± 10.5 (%), P = 0.01; however, the BMI in GH group was lower than in the control group, which was 24.5 ± 3.7 (%) vs. 24.9 ± 3.6 (%), P < 0.001. Fat/height and Fat/BSA were not significantly different between the two groups. Moreover, after adjusting for potential confounders, fat/LBM significantly correlated with GH (OR = 2.09, 95% CI, 1.11 to 3.93). The study revealed that fat/LBM significantly correlated with GH among Chinese adult population, which highlights that adiposity might be an important and potentially modifiable determinant of GH.

6.
Eur Respir J ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31619474

RESUMO

Epidemiological studies demonstrate an association between asthma and mental health disorders, although little is known about the shared genetics and causality of this association. Thus, we aim to investigate shared genetic and the causal link between asthma and mental health disorders.We conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between asthma from UK Biobank and 8 mental health disorders from Psychiatric Genomics Consortium, including: attention deficit hyperactivity disorder (ADHD), anxiety disorder (ANX), autism spectrum disorder, bipolar disorder, eating disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia, with a sample size of 7556 to 446 032.In the single trait genome-wide association analysis, we replicated 130 and discovered 31 novel independent loci that are associated with asthma. We identified that ADHD, ANX and MDD have strong genetic correlation with asthma at the genome-wide level. Cross-trait meta-analysis identified 7 loci jointly associated with asthma and ADHD, 1 loci with asthma and ANX and 10 loci with asthma and MDD. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, respiratory and hemic/immune system. Mendelian randomisation analyses suggested that ADHD and MDD (including 6.7% samples overlap with asthma) might increase the risk of asthma.This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between asthma and three mental health disorders (ADHD, ANX, and MDD). Such shared genetics implicate potential new biological functions that are in common among them.

7.
J Am Coll Cardiol ; 74(17): 2162-2174, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31648709

RESUMO

BACKGROUND: High resting heart rate (RHR) occurs in parallel with type 2 diabetes (T2D) and metabolic disorders, implying shared etiology between them. However, it is unknown if they are causally related, and no study has been conducted to investigate the shared mechanisms underlying these associations. OBJECTIVES: The objective of this study was to understand the genetic basis of the association between resting heart rate and cardiometabolic disorders/T2D. METHODS: This study examined the genetic correlation, causality, and shared genetics between RHR and T2D using LD Score regression, generalized summary data-based Mendelian randomization, and transcriptome wide association scan (TWAS) in UK Biobank data (n = 428,250) and summary-level data for T2D (74,124 cases and 824,006 control subjects) and 8 cardiometabolic traits (sample size ranges from 51,750 to 236,231). RESULTS: Significant genetic correlation between RHR and T2D (rg = 0.22; 95% confidence interval: 0.18 to 0.26; p = 1.99 × 10-22), and 6 cardiometabolic traits (fasting insulin, fasting glucose, waist-hip ratio, triglycerides, high-density lipoprotein, and body mass index; rg range -0.12 to 0.24; all p < 0.05) were observed. RHR has significant estimated causal effect on T2D (odds ratio: 1.12 per 10-beats/min increment; p = 7.79 × 10-11) and weaker causal estimates from T2D to RHR (0.32 beats/min per doubling increment in T2D prevalence; p = 6.14 × 10-54). Sensitivity analysis by controlling for the included cardiometabolic traits did not modify the relationship between RHR and T2D. TWAS found locus chr2q23.3 (rs1260326) was highly pleiotropic among RHR, cardiometabolic traits, and T2D, and identified 7 genes (SMARCAD1, RP11-53O19.3, CTC-498M16.4, PDE8B, AKTIP, KDM4B, and TSHZ3) that were statistically independent and shared between RHR and T2D in tissues from the nervous and cardiovascular systems. These shared genes suggested the involvement of epigenetic regulation of energy and glucose metabolism, and AKT activation-related telomere dysfunction and vascular endothelial aging in the shared etiologies between RHR and T2D. Finally, FADS1 was found to be shared among RHR, fasting glucose, high-density lipoprotein, and triglycerides. CONCLUSIONS: These findings provide evidence of significant genetic correlations and causation between RHR and T2D/cardiometabolic traits, advance our understanding of RHR, and provide insight into shared etiology for high RHR and T2D.

8.
Environ Res ; 179(Pt A): 108775, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31593837

RESUMO

BACKGROUND: Recent studies suggested an inverse association between exposures to perfluoroalkyl substances (PFASs) and bone mineral density (BMD). Whether exposures to PFASs are also associated with changes in BMD has not been examined. METHODS: Five major PFASs (perfluorooctanesulfonic acid, PFOS; perfluorooctanoic acid, PFOA; perfluorohexanesulfonic acid, PFHxS; perfluorononanoic acid, PFNA; perfluorodecanoic acid, PFDA) and BMD (g/cm2) at six bone sites (spine, total hip, femoral neck, hip intertrochanteric area, hip trochanter, and hip Ward's triangle area) were measured at baseline among 294 participants in the POUNDS-LOST study, a weight-loss trial, of whom a total of 175 participants had BMD measured at both baseline and year 2. Linear regression was used to model the differences or changes in BMD for each SD increment of PFAS concentrations. In a secondary analysis, interactions between PFASs and baseline body mass index (BMI), as well as a BMI-related genetic risk score (GRS) derived from 97 BMI-predicting SNPs were examined in relation to changes in BMD. RESULTS: At baseline, both PFOS and PFOA were significantly associated with lower BMD at several sites. For each SD increase of PFOS, the ßs (95% CIs) for BMD were -0.020(-0.037, -0.003) for spine, -0.013(-0.026, 0.001) for total hip, -0.014(-0.028, 0.000) for femoral neck, and -0.013(-0.026, 0.000) for hip trochanter. For PFOA, the corresponding figures were -0.021(-0.038, -0.004) for spine, -0.015(-0.029, -0.001) for total hip, and -0.015(-0.029, -0.002) for femoral neck. After adjusting for baseline covariates and 2-year weight change, higher baseline plasma concentrations of PFOS, PFNA, and PFDA were associated with greater reduction in BMD in the hip; the ßs (95% CIs) were -0.005(-0.009, -0.001), -0.006(-0.010, -0.001), and -0.005(-0.009, -0.001), respectively. Similar associations were found in hip intertrochanteric area for all PFASs except PFHxS, with ßs ranging from -0.006 for PFOA to -0.008 for PFOS and PFNA. Participants with a higher GRS tended to have less PFAS-related BMD decline in total hip (Pinteraction = 0.005) and the hip intertrochanteric area (Pinteraction = 0.021). There were similar PFAS-related BMD changes by baseline BMI levels, although the interactions did not achieve statistical significance. CONCLUSIONS: This study demonstrated that higher plasma PFAS concentrations were not only associated with a lower BMD at baseline, but also a faster BMD loss in a weight-loss trial setting. Genetic predisposition to larger body size may somewhat attenuate the deleterious effects of PFASs on BMD. Further exploration of the possible impact of PFAS exposures on bone density is warranted.

9.
Plast Reconstr Surg ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31577662

RESUMO

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid (HA), the incidence of HA embolism has also commensurately increased. HA embolism leads to serious complications including blindness, eye and eyelid movement disorders, skin necrosis and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for HA embolism by Intra-arterial thrombolysis (IAT) therapy. METHODS: In this study, we included 24 patients with a decrease in visual acuity and other complications induced by facial HA injection. These patients underwent emergency IAT therapy by injection of hyaluronidase (500-1,500 units) alone or hyaluronidase (750-1,500 units) combined with urokinase (100,000-250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: In the 24 patients, 10 patients (42%) ultimately had improvements to visual acuity, even in cases when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases the patients' facial skin necrosis was restored to nearly normal appearance. In addition, we found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSION: Our results indicate that IAT therapy is beneficial to patients suffering from blindness induced by HA embolism. IAT therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision , and was also beneficial in the recovery from other serious complications including eye movement disorder, eye edema, headaches, and skin necrosis.

10.
Nat Commun ; 10(1): 4267, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537805

RESUMO

Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in whole blood from 4170 individuals and map 4.7 million cis- and 630 thousand trans-meQTL variants targeting >120 thousand CpGs. Independent replication is performed in 1347 participants from two studies. By linking cis-meQTL variants with GWAS results for cardiovascular disease (CVD) traits, we identify 92 putatively causal CpGs for CVD traits by Mendelian randomization analysis. Further integrating gene expression data reveals evidence of cis CpG-transcript pairs causally linked to CVD. In addition, we identify 22 trans-meQTL hotspots each targeting more than 30 CpGs and find that trans-meQTL hotspots appear to act in cis on expression of nearby transcriptional regulatory genes. Our findings provide a powerful meQTL resource and shed light on DNA methylation involvement in human diseases.

11.
Nutr Metab Cardiovasc Dis ; 29(10): 1040-1049, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377179

RESUMO

BACKGROUND AND AIMS: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). METHODS AND RESULTS: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). CONCLUSION: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639.

12.
Clin Nutr ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31255351

RESUMO

BACKGROUND: We previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites associated with inflammatory diets among postmenopausal women, utilizing a robust study design that incorporates independent discovery and validation datasets. METHODS: This baseline cross-sectional investigation evaluated associations between continuous EDIP scores calculated from food frequency questionnaires and 448 log-transformed plasma metabolites as outcomes in multivariable-adjusted linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Metabolite discovery was conducted among 1109 Women's Health Initiative (WHI) Hormone Therapy trial participants and results were replicated in an independent dataset of 810 WHI Observational Study participants. Secondary analyses were stratified by standard body mass index (BMI, kg/m2) categories. In discovery and replication datasets statistical significance was based on false-discovery rate adjusted P < 0.05. RESULTS: After adjusting for energy intake, BMI, physical activity, and other confounding variables, 23 metabolites were significantly associated with EDIP score in the discovery dataset. Of these, the following ten were replicated: trigonelline, caffeine, acethylamino-6-amino-3-methyluracil, 7-methylxanthine, 1,7-dimethyluric acid, 3-methylxanthine, C18:3CE, glycine, associated with lower dietary inflammatory potential; whereas C52:3 triacylglycerol and linoleate associated with higher dietary inflammatory potential. Four of the ten were associated [glycine (inversely), caffeine, 1,7-dimethyluric acid, C52:3 triacylglycerol, (positively)], with C-reactive protein levels. In secondary analyses, associations showed differences by BMI category. Four metabolites, related to coffee/caffeine metabolism were inversely associated among normal weight women, and 83 metabolites associated with EDIP among overweight/obese women, including 40 (48%) that were also associated with C-reactive protein. CONCLUSION: Metabolites associated with coffee/caffeine and lipid metabolism may reflect the inflammatory potential of diet. Potential differences by BMI and the linkage to disease outcomes, require further study.

13.
Nat Commun ; 10(1): 3095, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300640

RESUMO

The nasal cellular epigenome may serve as biomarker of airway disease and environmental response. Here we collect nasal swabs from the anterior nares of 547 children (mean-age 12.9 y), and measure DNA methylation (DNAm) with the Infinium MethylationEPIC BeadChip. We perform nasal Epigenome-Wide Association analyses (EWAS) of current asthma, allergen sensitization, allergic rhinitis, fractional exhaled nitric oxide (FeNO) and lung function. We find multiple differentially methylated CpGs (FDR < 0.05) and Regions (DMRs; ≥ 5-CpGs and FDR < 0.05) for asthma (285-CpGs), FeNO (8,372-CpGs; 191-DMRs), total IgE (3-CpGs; 3-DMRs), environment IgE (17-CpGs; 4-DMRs), allergic asthma (1,235-CpGs; 7-DMRs) and bronchodilator response (130-CpGs). Discovered DMRs annotated to genes implicated in allergic asthma, Th2 activation and eosinophilia (EPX, IL4, IL13) and genes previously associated with asthma and IgE in EWAS of blood (ACOT7, SLC25A25). Asthma, IgE and FeNO were associated with nasal epigenetic age acceleration. The nasal epigenome is a sensitive biomarker of asthma, allergy and airway inflammation.


Assuntos
Asma/diagnóstico , Metilação de DNA/imunologia , Inflamação/diagnóstico , Mucosa Nasal/imunologia , Adolescente , Asma/genética , Asma/imunologia , Asma/patologia , Biomarcadores/análise , Criança , Ilhas de CpG/genética , Ilhas de CpG/imunologia , Epigênese Genética/imunologia , Epigenômica/métodos , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Masculino , Mucosa Nasal/patologia
15.
Mol Nutr Food Res ; 63(17): e1900140, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31291050

RESUMO

SCOPE: The relationship between red wine (RW) consumption and metabolism is poorly understood. It is aimed to assess the systemic metabolomic profiles in relation to frequent RW consumption as well as the ability of a set of metabolites to discriminate RW consumers. METHODS AND RESULTS: A cross-sectional analysis of 1157 participants is carried out. Subjects are divided as non-RW consumers versus RW consumers (>1 glass per day RW [100 mL per day]). Plasma metabolomics analysis is performed using LC-MS. Associations between 386 identified metabolites and RW consumption are assessed using elastic net regression analysis taking into consideration baseline significant covariates. Ten-cross-validation (CV) is performed and receiver operating characteristic curves are constructed in each of the validation datasets based on weighted models. A subset of 13 metabolites is consistently selected and RW consumers versus nonconsumers are discriminated. Based on the multi-metabolite model weighted with the regression coefficients of metabolites, the area under the curve is 0.83 (95% CI: 0.80-0.86). These metabolites mainly consisted of lipid species, some organic acids, and alkaloids. CONCLUSIONS: A multi-metabolite model identified in a Mediterranean population appears useful to discriminate between frequent RW consumers and nonconsumers. Further studies are needed to assess the contribution of these metabolites in health and disease.

16.
Int J Obes (Lond) ; 43(10): 1967-1977, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332276

RESUMO

BACKGROUND/OBJECTIVES: Acylcarnitines, intermediates of fatty acid oxidation, are known to be involved in obesity and insulin resistance. Since maternal prepregnancy overweight or obesity (OWO) is a recognized major risk factor for offspring OWO, we hypothesized that maternal plasma acylcarnitines may play a role in inter-generational OWO. SUBJECTS/METHODS: This study included 1402 mother-child pairs (1043 term, 359 preterm) recruited at birth from 1998-2013 and followed prospectively up to age 18 years at the Boston Medical Center. The primary outcomes were child OWO defined as BMI ≥ 85th percentile for age and sex. The primary exposures were maternal prepregnancy OWO defined as BMI ≥ 25 kg/m2 and maternal acylcarnitine levels measured in plasma samples collected soon after delivery using liquid chromatography-tandem mass spectrometry (LC-MS) in a targeted manner. RESULTS: Approximately 40% of the children in this study were OWO by age 5. Maternal OWO had a significant association with childhood OWO, both in term and preterm births. ß-hydroxybutyryl-carnitine (C4-OH) levels were significantly and positively associated with child OWO among term births after adjustment for potential confounders and multiple-comparisons. Children born to OWO mothers in the top tertile C4-OH levels were at the highest risk of OWO: OR = 3.78 (95%CI: 2.47, 5.79) as compared with those born to non-OWO mothers in the lowest tertile (P for interaction of maternal OWO and C4-OH = 0.035). In a four-way decomposition of mediation/interaction analysis, we estimated that C4-OH levels explained about 27% (se = 0.08) of inter-generational OWO risk (P = 0.001). In contrast, these associations were not observed in preterm births. CONCLUSIONS: In this U.S. urban low-income birth cohort, we provide further evidence of the inter-generational link of OWO and reveal the differential role of C4-OH in explaining the inter-generational obesity between term and preterm births. Further investigations are warranted to better understand and prevent the inter-generational transmission of OWO.

17.
Fertil Steril ; 112(2): 387-396.e3, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31146888

RESUMO

OBJECTIVE: To study whether increased body mass index is associated with altered expression of extracellular vesicle microRNAs (EV-linked miRNAs) in human follicular fluid. DESIGN: Cross-sectional study. SETTING: Tertiary-care university-affiliated center. PATIENT(S): One hundred thirty-three women undergoing in vitro fertilization (IVF) were recruited from January 2014 to August 2016. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): EV-linked miRNAs were isolated from follicular fluid and their expression profiles were measured with the use of the Taqman Open Array Human miRNA panel. EV-linked miRNAs were globally normalized and inverse-normal transformed. Associations between body mass index (BMI) and EV-linked miRNA outcomes were analyzed by means of multivariate linear regression and principal component analysis. RESULT(S): Eighteen EV-linked miRNAs were associated with an increase in BMI after adjusting for age, ethnicity, smoking status, and batch effects. Hsa-miR-328 remained significant after false discovery rate adjustments. Principal component analyses identified the first principal component to account for 40% of the variation in our EV-linked miRNA dataset, and adjusted linear regression found that the first principal component was significantly associated with BMI after multiple testing adjustments. Using Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we predicted gene targets of EV-linked miRNA in silico and identified PI3K-Akt signaling, ECM-receptor interaction, focal adhesion, FoxO signaling, and oocyte meiosis pathways. CONCLUSION(S): These results show that a 1-unit increase in BMI is associated with altered follicular fluid expression of EV-linked miRNAs that may influence follicular and oocyte developmental pathways. Our findings provide potential insight into a mechanistic explanation for the reduced fertility rates associated with increased BMI.

18.
Ann Plast Surg ; 83(3): 271-277, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31149905

RESUMO

BACKGROUND: Hypertrophic scars (HSs) generally form after injury to the deep layers of the dermis and are characterized by excessive collagen deposition. An increasing amount of evidence has determined that human adipose tissue-derived mesenchymal stem cells attenuate fibrosis in various conditions. We explored the effect and possible mechanism of chyle fat-derived stem cells (CFSCs) on HS formation. METHODS: Hypertrophic scar-derived fibroblasts (HSFs) and CFSCs were isolated from individual patients. Third-passage CFSCs were isolated and cultured using a mechanical emulsification method, and their surface CD markers were analyzed by flow cytometry. The adipogenic and osteogenic differentiation capacity of the CFSCs was determined using oil red O staining and alizarin red S staining, respectively. Then, the effects of CFSCs on HSFs were assessed in vitro. Hypertrophic scar-derived fibroblasts were treated with starvation-induced conditioned medium from the CFSCs (CFSC-CM). The change in HSF cellular behaviors, such as cell proliferation, migration, and protein expression of scar-related molecules, was evaluated by cell counting assay, scratch wound assay, enzyme-linked immunosorbent assay, and western blotting. All data were analyzed using SPSS 17.0. RESULTS: The CFSCs expressed CD90, CD105, and CD73 but did not express CD34, CD45, or CD31. The CFSCs differentiated into adipocytes and osteoblasts under the appropriate induction conditions. Chyle fat-derived stem cells conditioned medium inhibited HSF proliferation and migration. The in vitro and ex vivo studies revealed that CFSC-CM decreased type I collagen, type III collagen, and α smooth muscle actin expression. CONCLUSIONS: Our results suggest that CFSCs are associated with the inhibition of fibrosis in HSFs by a paracrine effect. The use of CFSC-CM may be a novel therapeutic strategy for HSs.

19.
Stroke ; 50(7): 1661-1668, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31167624

RESUMO

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.

20.
Nutrients ; 11(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072000

RESUMO

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56-0.64), 0.78 (95% CI 0.75-0.81) and 0.52 (95% CI 0.49-0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.

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