Objectives: Evidences from randomized clinical trials and meta-analysis have claimed an association between the use of soluble dietary fiber from psyllium and a cholesterol-lowering effect. However, there is still uncertainty as to the dose-response relationship and its long-term lipid-lowering efficacy. This meta-analysis was primarily conducted to address the dose-response relationship between psyllium and serum cholesterol level and time-dependent effect of psyllium in mild-to-moderate hypercholesterolemic subjects. Methods: Twenty-one studies, which enrolled a total of 1030 and 687 subjects receiving psyllium or placebo, respectively, were included in the meta-analysis. The studies were randomized placebo-controlled trials, double blinded or open label, on subjects with mild-to-moderate hypercholesterolemia. The dose of psyllium was between 3.0 and 20.4 g per day and intervention period was more than 2 weeks. Any type of diet background was permitted. Diet lead-in period was between 0 and 8 weeks.Results: Compared with placebo, consumption of psyllium lowered serum total cholesterol by 0.375 mmol/l (95% CI: 0.257-0.494 mmol/l), and LDL cholesterol by 0.278 mmol/l (95% CI: 0.213-0.312 mmol/l). With random-effect meta-regression, a significant dose-response relationship were found between doses (3-20.4 g/day) and total cholesterol or LDL cholesterol changes. Regression model of total cholesterol was À0.0222 þ 0.2061 Â log (dose þ 1), and that of LDL cholesterol was 0.0485 þ 0.1390 Â log (dose þ 1). There was a time effect of psyllium on total cholesterol (equation: 6.3640-0.0316 Â treatment period) and on LDL cholesterol (equation: 4.3134-0.0162 Â treatment period), suggesting that psyllium reduced serum total cholesterol more quickly than LDL cholesterol. Conclusions: Psyllium could produce dose-and time-dependent serum cholesterol-lowering effect in mild and moderate hypercholesterolemic patients and would be useful as an adjunct to dietary therapy for the treatment of hypercholesterolemia. (2009) 63, 821-827; doi:10.1038/ejcn.2008 published online 5 November 2008 Keywords: hypercholesterolemia; total cholesterol; LDL cholesterol; meta-analysis; randomized controlled trials European Journal of Clinical Nutrition IntroductionIn recent years, there has been growing interest in the use of dietary fibers in health maintenance and disease prevention (Petchetti et al., 2007). It has been speculated that a deficiency of soluble fibers in the Western diet might be contributing to the epidemics of coronary heart disease (CHD), diabetes mellitus and colonic cancer. Hypercholesterolemia has been identified as a prominent independent risk factor in the development of CHD. Soluble fibers, including those from psyllium husk, have been shown to augment the cholesterol-lowering effects of a low-fat diet in persons with hypercholesterolemia. Increasing dietary fiber has been recommended as a safe and practical approach for cholesterol reduction (NCEP ATPIII, 2001 andBrunner et al., 2007). Psyllium is one of the highest so...

Pin1 regulates a subset of phosphoproteins by isomerizing phospho-Ser/Thr-Pro motifs via a 'post-phosphorylation' mechanism. Here, we characterize TR3 as a novel Pin1 substrate, and the mitogenic function of TR3 depends on Pin1-induced isomerization. There are at least three phospho-Ser-Pro motifs on TR3 that bind to Pin1. The Ser95-Pro motif of TR3 is the key site through which Pin1 enhances TR3 stability by retarding its degradation. Pin1 can also catalyze TR3 through phospho-Ser431-Pro motif, which is phosphorylated by extracellular signalregulated kinase 2 (ERK2), resulting in enhanced TR3 transactivation. Furthermore, Pin1 not only facilitates TR3 targeting to the promoter of cyclin D2, a novel downstream target of TR3, but also promotes TR3 to recruit p300, thereby inducing cell proliferation. Importantly, we found that Pin1 is indispensable for TR3 to promote tumor growth both in vitro and in vivo. Our study thus suggests that Pin1 has an important role in cell proliferation by isomerizing TR3.

We constructed a novel hepatocellular carcinoma-specific conditionally replicative adenovirus (CRAd). This adenovirus, designated Ad.HS4.AFP.E1A/TRAIL, expresses E1A to mediate viral replication and TRAIL to enhance HCC-killing efficacy under the control of a modified AFP promoter. An insulator HS-4 was placed in front of the AFP promoter to enhance the fidelity of the heterologous promoter. This virus was shown to have specific cytolytic activity in AFP-expressing HCC cells in vitro. Furthermore, the replication efficiency of Ad.HS4.AFP.E1A/TRAIL correlated well with AFP expression of the host cells, showing a 100-fold and 1 000 000-fold decrease in the low-and non-AFP-expressing HCC cells, respectively, compared to the high AFP-expressing HCC cells. An increase in mRNA of TRAIL and the elevated Caspase-3 activity were also observed in Ad.HS4.AFP.E1A/TRAIL-infected HCC cells. These results indicated that TRAIL expression from the viral vector activated the Caspase-3 enzymatic capacity and the HCC cells were sensitive to TRAIL. In vivo, Ad.HS4.AFP.E1A/TRAIL effectively prevented the growth of low AFP-expressing BEL-7404 xenografts. These results indicate that Ad.HS4.AFP.E1A/TRAIL could provide a new strategy of gene therapy for HCC.

The left atrial posterior wall (LAPW) plays a critical role in atrial fibrillation, but the underlying mechanism remains unclear. In the present study, we sought to characterize the histological features of the LAPW. Different atrial regions were dissected from hearts of normal Sprague-Dawley rats and humans. Haematoxylin/eosin and van Gieson staining were used to analyse atrial cardiomyocyte arrangement and collagen distribution, respectively. Intercellular junctions were evaluated by transmission electron microscopy. In contrast with other atrial regions, the LAPW exhibited more disorganized cardiomyocytes, larger intercellular spaces and variable myocardial fibre arrangement. The proportion of collagen was significantly higher in the LAPW than in other atrial regions. Interestingly, desmosomes were sparse along with intercellular gaps in the LAPW. In summary, distinct disarrangement of cardiomyocytes and an abundance of collagen exist in the LAPW. The sparsity of desmosomes in the LAPW may be related to the heterogeneous distribution and separation of atrial myocytes.

The process, microstructure and mechanical properties of the chemical vapor deposition (CVD) multiple-layer coatings titanium carbide, titanium carbonitride, and titanium nitride (TiC,TiCN,TiN) on 9Crl8 (1%°C, 18%°C) steel were investigated, and the process has been successfully applied to high-precision bearings. The results indicate that CVD multiple-layer coating has fine-grained microstructure and good adhesion, i.e., the bond strength to substrate. CVD multiple-layer-coated 9Crl8 steel has good properties of friction-wear resistance and high rolling contact fatigue life. The coating follows perfectly the substrate deformation at the compressive load testing, and its bearing load capacity depends on the strength of substrate. After CVD-coated 9Crl8 steel balls were lapped in batches, their surface roughness was noticeably improved. The performances of the high-precision bearings with CVD-coated balls increased significantly. After 1000 h operation, no trace of wear on the CVD-coated balls and uncoated bearing races was observed.