26 research outputs found
Associations of whole, semi-skimmed, and skimmed milk with coronary artery disease and myocardial infarction.
CI, confidence interval; OR, odds ratio; SNP, single-nucleotide polymorphism; P-adjusted, FDR-corrected P.</p
S1-S18 Figs are included in the file.
BackgroundNumerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.MethodsFor the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.ResultsAfter adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261–12.432; P P P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.ConclusionOur findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.</div
S1-S12 Tables are included in the file.
BackgroundNumerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.MethodsFor the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.ResultsAfter adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261–12.432; P P P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.ConclusionOur findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.</div
Study design of MR.
Three core assumptions were as follows: (1) Relevance assumption, the genetic variants must be associated with exposure (milk with different fat content); (2) Independence assumption, the genetic variants should not be associated with confounders; (3) Exclusion restriction, the genetic variants must influence outcome (coronary artery disease and myocardial infarction) only via exposure.</p
Phosphine Catalyst-Controlled Cycloaddition or Dienylation Reactions of Trifluoromethyl Aryl Ketones with Bis-Substituted Allenoates
A chemoselective
phosphine-catalyzed cycloaddition or dienylation
reaction between trifluoromethyl-substituted ketones and bis-substituted
allenoates was described. Under the catalysis of triarylphosphine,
the reaction gave a range of trifluoromethylated tetrahydrofurans
with broad substrate tolerance and good to excellent stereoselectivity,
while the use of trialkylphosphine switched the reaction pathway to
furnish CF<sub>3</sub>-substituted dienyl tertiary alcohols chemoselectively.
Moreover, a preliminary study on the asymmetric version of the reaction
was also performed, which represents the first example of a phosphine-catalyzed
asymmetric reaction between allenoates and carbonyl compounds
Fatty acylation of phosphatidic acid promotes vesicle aggregation.
<p>Lipids were extracted after incubating 100 nmol PA or phosphatidylinositol (PI) with 100 nmol arachidonic acid the TIP30 complex or control eluates. Lipids were resuspended in homogenization buffer by sonication and were mixed with EGFR-DsRed and EYFP-Rab5a vesicles in <i>in vitro</i> fusion buffer at 37°C. Resulting vesicles were spotted on glass slides and images were taken using confocal microscope. Scale bars, 5 µm.</p
Fatty acylation of phosphatidic acid induce vesicle tethering and stacking.
<p>Effects of acylated PA on vesicle fusion were determined using electron microscope. Lipids were extracted after incubating PA with control immunoprecipitates (A), PA with immunopurified TIP30 complex (B), PA with recombinant TIP30, ACSL4, and Endo B1 (C) or PI with immunopurified TIP30 complex (D). Each of these lipids or triacylglycerol (E) was suspended in homogenization buffer and incubated on ice with EGFR-DsRed and EYFP-Rab5a vesicles. The resulting vesicles were examined using TEM. Scale bars, 500 nm.</p
Bacterially expressed recombinant TIP30, ACSL4 and Endo B1 can replace the TIP30 complex in promoting efficient vesicle fusion.
<p>(<b>A</b>) Recombinant proteins were expressed in BL21 cells and were purified using cobalt affinity resins. Eluted proteins were subjected to SDS-PAGE analysis followed by Coomassie blue staining. Images were acquired using a Li-Cor scanner. (<b>B</b>) EGFR-DsRed and EYFP-Rab5a vesicles were incubated with the indicated recombinant proteins (20 ng each) in the fusion buffer. Resulting fusion products were examined using confocal microscope. Scale bars, 5 µm. (<b>C</b>) Quantification of images represented in (B). Signal overlap was quantified using MBF_ImageJ. Pearson's colocalization coefficients were calculated from three independent experiments and converted to percentages. Data represent means ± SEM. **<i>P</i><0.01, ***<i>P</i><0.001; t test.</p
Arachidonyl group was transferred onto phosphatidic acid.
<p>(<b>A</b>) PA was incubated with the TIP30 protein complex in the fusion buffer. Resulting lipids were purified and subjected to flow injection negative scan in the range of 400–1400 u. A predominant peak of 699.5 was detected. Atomic mass: arachidonic acid, 304.5 u; 18:1 PA, 699.5 u. The lipids in the smaller peaks have molecular weights that do not match any of the expected PA derivatives. (<b>B</b>) The flow injection negative precursor scan for 303.2 u over a mass range of 400–1400 u. (<b>C</b>) The LC-C18 negative precursor scan for 303.2 u over a mass range of 400–1400 u. The lipids after the acylation reaction was extracted and chromatographed on a C-18 column to reduce possible adduction mechanisms of compounds detected in the flow injection negative precursor scan of 303.2 u.</p
Transmission electron microscopy analysis of products from in vitro vesicle fusion assays.
<p>(<b>A</b>) EGFR-DsRed and EYFP-Rab5a vesicles were incubated with immunopurified TIP30 complex in the fusion buffer with (right panel) or without (left panel) 100 nmol of arachidonic acid. Resulting vesicles were stained with uranyl acetate and examined using TEM. Scale bars, 500 nm. (<b>B</b>) The graphs show the percentages of vesicles with different diameters. At least 6 images from two independent experiments were counted. Data represent means ± SEM. n = 150; **<i>P</i><0.01, t test.</p