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EPA+DHA, but not ALA, Improved Lipids and Inflammation Status in Hypercholesterolemic Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.
Zhou, Q, Zhang, Z, Wang, P, Zhang, B, Chen, C, Zhang, C, Su, Y
Molecular nutrition & food research. 2019;(10):e1801157
Abstract
SCOPE To compare the effects of supplementary eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) versus α-linolenic acid (ALA) on lipid profiles, inflammatory status, and fatty acid composition of peripheral blood mononuclear cells (PBMCs) in hypercholesterolemic adults. METHODS AND RESULTS A randomized, controlled, double-blind trial is conducted to examine the effects of consumption of control oil, 4.2 g/d ALA, 7.2 g/d ALA, 1.8 g/d DHA+EPA, or 3.6 g/d EPA+DHA for 12 weeks on lipid profiles, fatty acid composition of PBMCs and in vitro production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by PBMCs in 123 subjects with hypercholesteremia. After the intervention, subjects who receive a low and high dose of DHA/EPA experience 11.99% and 15.78% decreases in triglycerides which is significantly different from that of the control group (p < 0.05). The in vitro study indicates that supplementation of high-dose DHA+EPA induces the greatest decrease of IL-6 production by PBMCs relative to other groups (p = 0.046). ALA intervention significantly increases the PBMCs composition of ALA but not EPA/DHA. CONCLUSION EPA+DHA, but not ALA, improves lipids and inflammation status in hypercholesterolemic adults. Supplementation of ALA does not increase the PBMCs composition of EPA/DHA in middle-aged to elderly Chinese.
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The association between the SLCO1B1, apolipoprotein E, and CYP2C9 genes and lipid response to fluvastatin: a meta-analysis.
Xiang, Q, Zhang, X, Ma, L, Hu, K, Zhang, Z, Mu, G, Xie, Q, Chen, S, Cui, Y
Pharmacogenetics and genomics. 2018;(12):261-267
Abstract
OBJECTIVE The aim of this study was to determine the impact of the SLCO1B1, apolipoprotein E (ApoE), and CYP2C9 genotypes on the lipid-lowering efficacy of fluvastatin. METHODS We performed electronic searches on the PubMed, Embase, and Cochrane Library databases to identify studies published through October 2017. Studies that reported the effect estimates with 95% confidence intervals (CIs) of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein were included so that the different genotype categories could be compared. Weighted mean difference (WMD) was used to summarize the effect estimates. RESULTS Six studies, involving a total of 1171 individuals, were included in the final analysis. We noted that the patient carrier SLCO1B1 521TT was associated with greater change in TC (WMD: -2.98; 95% CI: -5.12 to -0.84; P=0.006) and LDL (WMD: -5.58; 95% CI: -10.64 to -0.52; P=0.031) compared with 521TC or CC. Furthermore, the patient carrier ApoE*2/*3 showed more change in high-density lipoprotein compared with ApoE*3/*3 (WMD: 18.76; 95% CI: 8.97-28.55; P<0.001) and ApoE*3/*4 or *4/*4 (WMD: 22.51; 95% CI: 0.98-44.04; P=0.040). Finally, the CYP2C9 genotypes showed no correlation with the effects of fluvastatin on TC, triglyceride, and LDL. CONCLUSION The findings of this study suggested that the SLCO1B1 and ApoE polymorphisms could influence the lipid-lowering effect of fluvastatin, whereas the CYP2C9 genotypes were not associated with the therapeutic effects of fluvastatin.
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Change in lipid profile and risk of new-onset atrial fibrillation in patients with chronic heart failure: A 3-year follow-up observational study in a large Chinese hospital.
Liu, C, Geng, J, Ye, X, Yuan, X, Li, A, Zhang, Z, Xu, B, Wang, Y
Medicine. 2018;(39):e12485
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Abstract
In chronic heart failure (CHF), new-onset atrial fibrillation (AF) is associated with increased morbidity and mortality. We aimed to evaluate the influence of dyslipidemia on the incidence of new-onset AF in patients with CHF.In this single-center observational study, 308 patients with CHF and no history of AF were followed-up for 3 years. Of the 291 patients who attended the 1-year follow-up, 78 had developed AF (AF group; 10 deaths), while 213 had not (sinus rhythm [SR] group). Changes in lipid profile (ΔTC for total cholesterol and ΔLDLc for low-density lipoprotein cholesterol) were analyzed.The groups differed significantly regarding the decrease in lipid levels from baseline to the 1-year follow-up (AF vs SR: for ΔLDLc, 23.35 vs 7.80 mg/dL, P = .02; for ΔTC, 23.95 vs -2.76 mg/dL, P = .001). At the 3-year follow-up, new-onset AF was noted in 21 of the 188 living patients in the SR group. Cox proportional hazards analysis revealed ΔLDLc and ΔTC as independent risk factors for new-onset AF (hazard ratio, 1.018 and 1.013, respectively, per standard deviation increment), with higher incidence of new-onset AF for ΔTC > 9.65 mg/dL (P = .02) and for ΔLDLc > 9.73 mg/dL (P = .005).In CHF, pronounced decrease in LDLc and TC is associated with new-onset AF.
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Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation.
Liao, C, Zhang, Z, Kale, J, Andrews, DW, Lin, J, Li, J
Scientific reports. 2016;:29502
Abstract
Helix α9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the α9 dimer in a MOM model - using computer simulations supplemented with site-specific mutagenesis and crosslinking of the α9 helices. Our data not only confirmed the critical membrane environment for the α9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The corroborating evidence from simulations and experiments suggests that, helix α9 assists Bax activation via the dimer heterogeneity and interactions with specific MOM lipids, which eventually facilitate proteolipidic pore formation in apoptosis regulation.
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Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in postmenopausal women: a randomized clinical trial in Beijing.
Zheng, S, Wu, Y, Zhang, Z, Yang, X, Hui, Y, Zhang, Y, Chen, S, Deng, W, Liu, H, Ekangaki, A, et al
Chinese medical journal. 2003;(8):1127-33
Abstract
OBJECTIVE To determine the effects of raloxifene hydrochloride (RLX) on bone mineral density (BMD), bone metabolism markers and serum lipids in healthy postmenopausal women in Beijing. METHODS A multicenter, randomized, double-blind, placebo-controlled study was conducted in a total of 204 healthy postmenopausal women (age 59.5 +/- 5.0 years and weight 62.8 +/- 8.7 kg) treated with either RLX 60 mg (n = 102) or placebo (n = 102) daily for 12 months. BMD, serum lipids, and bone markers were measured before and after drug administration. RESULTS Compared with placebo, RLX produced a significant increase in both total lumbar spine and total hip BMD. For the lumbar spine, percentage increase in total BMD was 2.3% with RLX compared with a decrease of 0.1% with placebo (P < 0.001). Corresponding values for total hip BMD were a 2.5% increase for RLX and a 1.1% increase for placebo (P = 0.011). For biochemical markers of bone metabolism, serum osteocalcin and C-telopeptide, percentage decreases were 27.65% and 24.02% in RLX-treated subjects. Corresponding values in placebo were a 10.64% decrease and a 15.75% increase (RLX compared with placebo, both P < 0.001). For total cholesterol and low-density lipoprotein cholesterol levels, percentage decreases were 6.44% and 34.58% in the RLX-treated group. Corresponding values in placebo-treated patients were a 1.44% increase and a 19.07% decrease (RLX compared with placebo, both P < 0.001). No differences were found for high-density lipoprotein cholesterol or triglyceride levels between the two groups. Only 5 subjects discontinued early owing to an adverse event (3 in the RLX group and 2 in the placebo group). CONCLUSIONS This study confirms that RLX exerts positive effects on the skeleton, increasing BMD and decreasing biochemical markers of bone metabolism, and has a positive effect on the overall serum lipid profile in postmenopausal women in China.