BackgroundDyslipidemia is one of the most important factors for coronary artery disease (CAD). Atherogenic index of plasma (AIP) is a novel indicator involved in dyslipidemia. However, the relation between AIP and CAD in postmenopausal women remains unclear. We hypotheses that AIP is a strong predictive indicator of CAD in postmenopausal women.MethodsA propensity score matching case–control study including 348 postmenopausal CAD cases and 348 controls was conducted in the present study.ResultsCompared with controls, CAD patients had higher levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (APOB), but lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (APOA-1). The values of nontraditional lipid profiles, including non-HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C (atherogenic index, AI), TC∗TG∗LDL/HDL-C (lipoprotein combine index, LCI), log(TG/HDL-C) (atherogenic index of plasma, AIP) and APOB/APOA-1 were all significantly higher in the CAD patients. The results of Pearson correlation analyses showed AIP was positively and significantly correlated with TC (r = 0.092, P < 0.001), TG (r = 0.775, P = 0.015), APOB (r = 0.140, P < 0.001), non-HDL-C (r = 0.295, P < 0.001), TC/HDL-C (r = 0.626, P < 0.001), LDL-C/HDL-C (r = 0.469, P < 0.001), AI (r = 0.626, P < 0.001), LCI (r = 0.665, P < 0.001), APOB/APOA-1(r = 0.290, P < 0.001) and was negatively correlated with APOA-1 (r = − 0.278, P < 0.001) and HDL-C (r = − 0.665, P < 0.001). In the multivariate logistic regression analysis, AIP was an independent predictor of CAD. After adjusting for the traditional clinical prognostic factors including diabetes and hypertension, we found AIP could be an independent risk factor for CAD (odds ratio [OR], 3.290; 95% confidence interval [CI], 1.842–5.877, P < 0.001). After adjusting for multiple clinical factors include diabetes, hypertension, smoking, heart ratio, fasting blood glucose, we found AIP also could a powerful risk factor, OR = 3.619, 95%CI (2.003–6.538), P < 0.001.ConclusionThe present study indicated that AIP might be a strong marker for predicting the risk of CAD in postmenopausal women.

The upper limit of iodine intake during early pregnancy in an iodine-sufficient region should not exceed UIC 250 μg/L, because this is associated with a significantly high risk of subclinical hypothyroidism, and a UIC of 500 μg/L should not be exceeded, as it is associated with a significantly high risk of isolated hypothyroxinemia.

Fused in sarcoma (FUS) is involved in many processes of RNA metabolism. FUS and another RNA binding protein, TDP-43, are implicated in amyotrophic lateral sclerosis (ALS). It is significant to characterize the RNA recognition motif (RRM) of FUS as its nucleic acid binding properties are unclear. More importantly, abolishing the RNA binding ability of the RRM domain of TDP43 was reported to suppress the neurotoxicity of TDP-43 in Drosophila. The sequence of FUS-RRM varies significantly from canonical RRMs, but the solution structure of FUS-RRM determined by NMR showed a similar overall folding as other RRMs. We found that FUS-RRM directly bound to RNA and DNA and the binding affinity was in the micromolar range as measured by surface plasmon resonance and NMR titration. The nucleic acid binding pocket in FUS-RRM is significantly distorted since several critical aromatic residues are missing. An exceptionally positively charged loop in FUS-RRM, which is not found in other RRMs, is directly involved in the RNA/DNA binding. Substituting the lysine residues in the unique KK loop impaired the nucleic acid binding and altered FUS subcellular localization. The results provide insights into the nucleic acid binding properties of FUS-RRM and its potential relevance to ALS.

BackgroundSerum amyloid A protein (SAA) is not only an inflammatory factor, but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein (HDL), which has been linked to atherosclerosis. However, the relationship between genetic polymorphisms of SAA and the intima-media thickness (IMT) of the common carotid artery in healthy subjects remains unclear. We investigated the role of SAA1 and SAA2 gene polymorphisms with IMT in a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study.Methodology/Principal FindingsAnthropometric and B-mode ultrasound of the carotid IMT were measured in 1914 subjects (849 men; 1065 women) recruited from seven cities in Xinjiang province, (western China). Four SNPs (rs12218, rs2229338, rs1059559, and rs2468844) were genotyped by use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The SNP rs12218 was associated with carotid IMT by analyses of a dominate model (P<0.001) and additive model (P = 0.003), and the difference remained significant after multivariate adjustment (P = 0.008, P<0.001, respectively). This relationship was also observed in rs2468844 after multivariate adjustment by recessive model analysis (P = 0.011) but this was not observed in rs2229338 and rs1059559 before and after multivariate adjustment. These associations were not modified by serum HDL concentration. Furthermore, there were significant interactions between rs2468844 and rs12218 (interaction P<0.001) and rs2229338 (interaction P = 0.001) on carotid IMT.Conclusion/SignificanceBoth rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects.

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Toll-like receptor 3 (TLR3), a member of the pathogen recognition receptors, is widely expressed in various cells and has been shown to activate immune signaling pathways by recognizing viral double-stranded RNA. Recently, it was reported that the activation of TLR3 induced apoptosis in some cells, but the detailed molecular mechanism is not fully understood. In this study, we found that in endothelial cells polyinosinic-polycytidylic acid (poly(I-C)) induced dose-and time-dependent cell apoptosis, which was elicited by TLR3 activation, as TLR3 neutralization and down-regulation repressed the apoptosis. Poly(I-C) induced the activation of both caspases 8 and 9, indicating that TLR3 triggered the signaling of both the extrinsic and intrinsic apoptotic pathways. Poly(I-C) up-regulated tumor necrosis factor-related apoptosis-inducing ligand and its receptors, death receptors 4/5, resulting in initiating the extrinsic pathway. Furthermore, poly(I-C) down-regulated anti-apoptotic protein, B cell lymphoma 2 (Bcl-2), and up-regulated Noxa, a key Bcl-2 homology 3-only antagonist of Bcl-2, leading to the priming of the intrinsic pathway. A p53-related protein, the transactivating p63 isoform ␣ (TAp63␣), was induced by TLR3 activation and contributed to the activation of both the intrinsic and extrinsic apoptotic pathways. Both the cells deficient in p63 gene expression by RNA interference and cells that overexpressed the N-terminally truncated p63 isoform ␣ (⌬Np63␣), a dominant-negative variant of TAp63␣, by gene transfection, survived TLR3 activation. Taken together, TAp63␣ is a crucial regulator downstream of TLR3 to induce cell death via death receptors and mitochondria.

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OBJECTIVE. Recent study suggested that the genetic polymorphisms of serum amyloid A protein (SAA) were linked to cardiovascular disease (CVD). However, the relationship between genetic polymorphisms of SAA and ankle-to-brachial index (ABI) in healthy subjects has not been studied. We investigated the role of the SAA1 gene polymorphisms with ABI. METHODS AND RESULTS. All participants were selected from a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study. Four single-nucleotide polymorphisms (SNPs; rs12218, rs4638289, rs7131332 and rs11603089) were genotyped by use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. There was significant difference between CC genotype and CT genotype [(1.066 ± 0.113) vs (1.119 ± 0.096), p = 0.008], CC genotype and TT genotype [(1.066 ± 0.113) vs (1.127 ± 0.095), p = 0.002] of rs12218 in ABI, and these differences remained significant after adjustment for the sex, age, blood pressure, BMI, alcohol intake, smoking and high-density lipoprotein (HDL) [(1.073 ± 0.018) vs (1.122 ± 0.007), p = 0.012; (1.073 ± 0.018) vs (1.124 ± 0.006), p = 0.009), respectively]. These relationships were not found in rs874957, rs7950019 and rs11603089 before and after multivariate adjustment. CONCLUSIONS. CC genotype of rs12218 in the SAA1 gene was associated with decreased ABI in Chinese Han subjects, which indicated that the carriers of CC genotype of rs12218 have high risk of peripheral arterial disease.