Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population

Summary Background & aims The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. Methods A total of 2671 participants, aged 40–75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. Results After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2–4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). Conclusions Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings

Effects of Toroidal Magnetic Fields on the Thermal Instability of Thin Accretion Disks

The standard thin disk model predicts that when the accretion rate is moderately high, the disk is radiation-pressure-dominated and thermally unstable. However, observations indicate the opposite, namely the disk is quite stable. We present an explanation in this work by taking into account the role of the magnetic field which was ignored in the previous analysis

Extracellular RNA in a single droplet of human serum reflects physiologic and disease states.

Extracellular RNAs (exRNAs) are present in human serum. It remains unclear to what extent these circulating exRNAs may reflect human physiologic and disease states. Here, we developed SILVER-seq (Small Input Liquid Volume Extracellular RNA Sequencing) to efficiently sequence both integral and fragmented exRNAs from a small droplet (5 μL to 7 μL) of liquid biopsy. We calibrated SILVER-seq in reference to other RNA sequencing methods based on milliliters of input serum and quantified droplet-to-droplet and donor-to-donor variations. We carried out SILVER-seq on more than 150 serum droplets from male and female donors ranging from 18 y to 48 y of age. SILVER-seq detected exRNAs from more than a quarter of the human genes, including small RNAs and fragments of mRNAs and long noncoding RNAs (lncRNAs). The detected exRNAs included those derived from genes with tissue (e.g., brain)-specific expression. The exRNA expression levels separated the male and female samples and were correlated with chronological age. Noncancer and breast cancer donors exhibited pronounced differences, whereas donors with or without cancer recurrence exhibited moderate differences in exRNA expression patterns. Even without using differentially expressed exRNAs as features, nearly all cancer and noncancer samples and a large portion of the recurrence and nonrecurrence samples could be correctly classified by exRNA expression values. These data suggest the potential of using exRNAs in a single droplet of serum for liquid biopsy-based diagnostics

Cohort Profile: The Jiaxing Birth Cohort in China.

This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Oxford University Press.This work was supported by the National Basic Research Program of China (973 Program: 2015CB553604); by National Natural Science Foundation of China (NSFC: 81273054); and by the Ph.D. Programs Foundation of Ministry of Education of China (20120101110107)

Revisiting the Thermal Stability of Radiation-dominated Thin Disks

The standard thin disk model predicts that when the accretion rate is over a small fraction of the Eddington rate, which corresponds to L \ga 0.06 L_{Edd}, the inner region of the disk is radiation-pressure-dominated and thermally unstable. However, observations of the high/soft state of black hole X-ray binaries with luminosity well within this regime (0.01L_{Edd} \la L \la 0.5L_{Edd}) indicate that the disk has very little variability, i.e., quite stable. Recent radiation magnetohydrodynamic simulations of a vertically stratified shearing box have confirmed the absence of the thermal instability. In this paper, we revisit the thermal stability by linear analysis, taking into account the role of magnetic field in the accretion flow. By assuming that the field responses negatively to a positive temperature perturbation, we find that the threshold of accretion rate above which the disk becomes thermally unstable increases significantly compared with the case of not considering the role of magnetic field. This accounts for the stability of the observed sources with high luminosities. Our model also presents a possible explanation as to why only GRS 1915+105 seems to show thermally unstable behavior. This peculiar source holds the highest accretion rate (or luminosity) among the known high state sources, which is well above the accretion rate threshold of the instability.Comment: 13 pages, 2 figures, accepted by Ap

Nutritional Biomarkers, Gene-Diet Interaction, and Risk Factors for Type 2 Diabetes

10.1155/2016/8610501Journal of Diabetes Research2016861050

Maternal Blood Pressure Rise During Pregnancy and Offspring Obesity Risk at 4 to 7 Years Old: The Jiaxing Birth Cohort.

CONTEXT: Maternal hypertensive disorders during pregnancy are suggested to affect obesity risk in offspring. However, little is known about the prospective association of rise in maternal blood pressure within normal range during pregnancy with this risk for obesity. OBJECTIVE: To clarify the associations of diastolic and systolic blood pressure during pregnancy among normotensive women with the risk for obesity in offspring. DESIGN: Prospective cohort study. SETTING: Southeast China. PARTICIPANTS: Up to 2013, a total of 88,406 mother-child pairs with anthropometric measurements of offspring age 4 to 7 years were included in the present analysis. MAIN OUTCOME MEASURES: Overweight/obesity risk in offspring. RESULTS: Among normotensive women, second- and third-trimester diastolic and systolic blood pressures were positively associated with risk for overweight/obesity in offspring: odds ratios per 10-mm Hg higher second- and third-trimester diastolic blood pressure were 1.05 [95% confidence interval (CI), 1.01 to 1.09] and 1.05 (95% CI, 1.02 to 1.10), respectively, and for systolic blood pressure were 1.08 (95% CI, 1.05 to 1.11) and 1.06 (95% CI, 1.03 to 1.09). Each 10-mm Hg greater rise in blood pressure between first and third trimesters was associated with a higher risk for offspring overweight/obesity: diastolic, 1.06 (95% CI, 1.01 to 1.10); systolic, 1.05 (95% CI, 1.02 to 1.07). Among all women (combining normotensive and hypertensive women), maternal hypertension in the second and third trimesters was associated with 49% and 14% higher risks for overweight/obesity in offspring, respectively. CONCLUSIONS: These results suggest that rise in maternal blood pressure during pregnancy and hypertension during pregnancy, independent of maternal body size before pregnancy, are risk factors for offspring childhood obesity

Lifestyle and metabolic factors for nonalcoholic fatty liver disease:Mendelian randomization study

The risk factors for nonalcoholic fatty liver disease (NAFLD) have not been clearly identified. We conducted a Mendelian randomization (MR) study to explore this. Independent genetic variants strongly associated with 5 lifestyle and 9 metabolic factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for NAFLD were obtained from a GWAS meta-analysis of 8434 cases and 770,180 non-cases (discovery dataset) and another GWAS meta-analysis of 1483 cases and 17,781 non-cases (replication dataset). Univariable and multivariable MR analyses were performed. There were associations with NAFLD for lifetime smoking index (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.31-1.93 per SD-increase), body mass index (BMI, OR 1.33, 95% CI 1.23-1.43 per SD-increase), waist circumference (OR 1.82; 95% CI 1.48-2.24 per SD-increase), type 2 diabetes (OR 1.21, 95% CI 1.15-1.27 per unit increase in log-transformed odds), systolic blood pressure (OR 1.17; 95% CI 1.07-1.26 per 10 mmHg increase), high-density lipoprotein cholesterol (OR 0.84, 95% CI 0.77-0.90 per SD-increase), and triglycerides (OR 1.23, 95% CI 1.15-1.33 per SD-increase). The associations for type 2 diabetes, systolic blood pressure, triglycerides, but not for high-density lipoprotein cholesterol remained strong after adjusting for genetically-predicted BMI. Genetic liability to type 2 diabetes mediated 51.4% (95% CI 13.4-89.3%) of the BMI-effects on NAFLD risk. There were suggestive inverse associations of genetically-predicted alcohol, coffee, and caffeine consumption, and vigorous physical activity with NAFLD risk. This study identified several lifestyle and metabolic factors that may be causally implicated in NAFLD

Upregulation of microRNA-125b contributes to leukemogenesis and increases drug resistance in pediatric acute promyelocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Although current chemotherapy regimens have remarkably improved the cure rate of pediatric acute promyelocytic leukemia (APL) over the past decade, more than 20% of patients still die of the disease, and the 5-year cumulative incidence of relapse is 17%. The precise gene pathways that exert critical control over the determination of cell lineage fate during the development of pediatric APL remain unclear.</p> <p>Methods</p> <p>In this study, we analyzed <it>miR-125b </it>expression in 169 pediatric acute myelogenous leukemia (AML) samples including 76 APL samples before therapy and 38 APL samples after therapy. The effects of enforced expression of <it>miR-125b </it>were evaluated in leukemic cell and drug-resistant cell lines.</p> <p>Results</p> <p><it>miR-125b </it>is highly expressed in pediatric APL compared with other subtypes of AML and is correlated with treatment response, as well as relapse of pediatric APL. Our results further demonstrated that <it>miR-125b </it>could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor BCL2-antagonist/killer 1 (Bak1). Remarkably, <it>miR-125b </it>was also found to be up-regulated in leukemic drug-resistant cells, and transfection of a <it>miR-125b </it>duplex into AML cells can increase their resistance to therapeutic drugs,</p> <p>Conclusions</p> <p>These findings strongly indicate that <it>miR-125b </it>plays an important role in the development of pediatric APL at least partially mediated by repressing BAK1 protein expression and could be a potential therapeutic target for treating pediatric APL failure.</p

Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.This study was funded by the National Basic Research Program of China (973 Program: 2015CB553604); by National Natural Science Foundation of China (NSFC: 81273054); and by the Ph.D. Programs Foundation of Ministry of Education of China (20120101110107). J.-S.Z. acknowledges support from MRC Epidemiology Unit (MC_UU_12015/5) and the Cambridge Initiative – Nutrition (RG71466, SJAH/004). F.I. acknowledges support from the MRC Epidemiology Unit (MC_UU_12015/5).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2952