Proteomics Analysis of Lipid Metabolism and Inflammatory Response in the Liver of Rabbits fed on a High Cholesterol Diet.

In this study, we aimed to analyze the proteomics of the liver in rabbits on a high cholesterol diet (HCD). We randomly divided New Zealand white rabbits into the normal diet group and the HCD group. We established the atherosclerosis model and measured plasma cholesterol and triglycerides. The model was successfully established using ultrasound examination and histopathological staining of the intima of aorta and liver of the two groups of rabbits. The differential proteins in the rabbit liver were analyzed using Tandem Mass Tags proteomic analysis technology. Finally, we used western blot to verify the reliability of proteomics. The results showed that compared with the control group, the serum lipid levels of rats in the HCD group was significantly increased, and the pathological sections showed the formation of atherosclerotic plaques in the aorta, inflammation, and adipose lesions in the liver. Proteomic analysis of the liver revealed 149 differences in HCD-expressed protein, which is mainly involved in inflammation and regulation of lipid and sugar metabolism. In addition, we verified differentially expressed liver proteins in the HCD group using western blot. We found that HCD caused lipid accumulation, abnormal glucose metabolism, and inflammatory response in the liver.

The negative association between serum albumin levels and coronary heart disease risk in adults over 45 years old: a cross-sectional survey.

This study aimed to assess the correlation between serum albumin levels and coronary heart disease (CHD) risk in adults aged over 45 years. This cross-sectional study used the non-institutionalized US population from the National Health and Nutrition Examination Survey (NHANES 2011-2018) as the sample source. Multiple logistic regression was performed to evaluate the association between serum albumin levels and CHD risk. Smooth curve fitting was performed to explore potential nonlinear relationships. When nonlinear relationships were found, a recursive algorithm was used to calculate inflection points. Additionally, a piecewise logistic regression model was constructed. After adjusting for confounders, multiple logistic regression and smooth curve fitting indicated an inverse association between serum albumin levels and CHD risk [OR = 0.970, 95% CI = (0.948, 0.992)]. Subgroup analysis revealed that the negative correlation was statistically significant in the population of female patients, over 60 years, with hypertension, without diabetes. There was a correlation between serum albumin levels and CHD risk. Lower serum albumin levels were associated with a higher CHD risk.

Changes in gut microbiota composition and diversity associated with post-cholecystectomy diarrhea.

BACKGROUND: Post-cholecystectomy diarrhea (PCD) frequently occurs in patients following gallbladder removal. PCD is part of the post-cholecystectomy (PC) syndrome, and is difficult to treat. After cholecystectomy, bile enters the duodenum directly, independent of the timing of meals. The interaction between the bile acids and the intestinal microbes is changed. Therefore, the occurrence of PCD may be related to the change in microbiota. However, little is known about the relationship between the gut microbiota and PCD. AIM: To better understand the role of the gut microbiota in PCD patients. METHODS: Fecal DNA was isolated. The diversity and profiles of the gut microbiota were analyzed by performing high-throughput 16S rRNA gene sequencing. The gut microbiota were characterized in a healthy control (HC) group and a PC group. Subsequently, the PC group was further divided into a PCD group and a post-cholecystectomy non-diarrhea group (PCND) according to the patients' clinical symptoms. The composition, diversity and richness of microbial communities were determined and compared. RESULTS: In the PC and HC groups, 720 operational taxonomic units (OTUs) were identified. The PC group had fewer OTUs than the HC group. ß-diversity was decreased in the PC group. This indicated decreased microbial diversity in the PC group. Fifteen taxa with differential abundance between the HC and PC groups were identified. In the PCD group compared to the PCND group, significant decreases in microbial diversity, Firmicutes/Bacteroidetes ratio, and richness of probiotic microbiota (Bifidobacterium and Lactococcus), and an increase in detrimental microbiota (Prevotella and Sutterella) were observed. Moreover, a negative correlation was found between Prevotella and Bifidobacterium. Using a Kyoto Encyclopedia of Genes and Genomes functional analysis, it was found that the abundances of gut microbiota involved in lipid metabolism pathways were markedly lower in the PCD group compared to the PCND group. CONCLUSION: This study demonstrated that gut dysbiosis may play a critical role in PCD, which provides new insights into therapeutic options for PCD patients.

JHDM1D-AS1 aggravates the development of gastric cancer through miR-450a-2-3p-PRAF2 axis.

AIMS: To investigate the molecular function and mechanisms of JHDM1D antisense 1 (JHDM1D-AS1) during gastric cancer (GC) progression. MATERIALS AND METHODS: The qPCR assay was used to detect the JHDM1D-AS1 and miR-450a-2-3p expression levels in GC tissues and cell lines. Bioinformatics analysis was used for exploring the lncRNA-microRNA-mRNA interaction network. We performed dual-luciferase reporter assay and qPCR assay in order to validate the direct interactions. We explored the JHDM1D-AS1 and miR-450a-2-3p on GC progression by using JHDM1D-AS1 siRNA and miR-450a-2-3p inhibitor; in vitro CCK-8 assay, colony formation assay, and invasion assay were conducted. Further, in vivo animal experiments were performed, and the expression levels of miR-450a-2-3p and PRAF2 in the tumor tissues were detected using qPCR and western blot analysis. KEY FINDINGS: The expression levels of JHDM1D-AS1 and miR-450a-2-3p in GC tissues and cell lines were higher and lower as compared to those in the corresponding normal controls, respectively. Moreover, high levels of JHDM1D-AS1 were closely related with metastasis and the GC TNM stage. Functionally, JHDM1D-AS1 depletion caused an obvious reduction in cell proliferation and invasion both in vitro and in vivo, while the addition of miR-450a-2-3p inhibitor could nullify these effects. Mechanically, JHDM1D-AS1 promoted GC progression via the sponging of miR-450a-2-3p in order to increase PRAF2 expression. SIGNIFICANCE: The present results showed that the increased expression of JHDM1D-AS1 was closely associated with tumor progression of GC. JHDM1D-AS1/miR-450a-2-3p/PRAF2 axis may be a promising target for GC treatment.

1-(4-Amino-2-hydroxyphenyl)ethanone from Phomopsis liquidambari showed quorum sensing inhibitory activity against Pseudomonas aeruginosa.

Phomopsis liquidambari S47 is an endophytic fungus isolated from the leaves of Punica granatum. Here, we are the first to report a quorum sensing (QS) inhibitor 1-(4-amino-2-hydroxyphenyl)ethanone (AHE) isolated and identified from the metabolites of P. liquidambari S47. Exposure to AHE at sub-MIC concentrations notably suppressed the secretion of acyl-homoserine lactones and virulence factors in Pseudomonas aeruginosa PAO1. To investigate the metabolic variations of P. aeruginosa PAO1 exposed to AHE, magnetic resonance imaging-based metabolomic analysis was performed. AHE treatment created a disturbance in the QS system by suppressing the expressions of QS-related genes. The disturbed QS system resulted in the inhibited activity of antioxidant enzymes and thus enhanced oxidative stress. The vegetable infection assay showed that the virulence of P. aeroginosa PAO1 was attenuated which could be due to the impacts to the amino acid and nucleotide metabolism by enhanced oxidative stress. These findings suggest that AHE has a potential to become an antivirulence "agent" to tackle P. aeruginosa infection. KEY POINTS: • AHE treatment inhibited AHL secretion and virulence factors production. • AHE treatment aggravated oxidative stress and disturbed metabolism. • AHE suppressed QS-related gene expressions and reduced virulence of P. aeruginosa.

1-(4-Amino-2-Hydroxyphenyl)Ethenone Suppresses Agrobacterium tumefaciens Virulence and Metabolism.

The impact of 1-(4-amino-2-hydroxyphenyl)ethanone (AHPE) from the metabolites of endophytic fungus Phomopsis liquidambari on quorum sensing (QS) of Agrobacterium tumefaciens was evaluated for the first time in this study. Exposure to AHPE at concentrations ranging from 12.5 to 50 µg/mL, the ß-galactosidase activity, acyl-homoserine lactone level, swimming motility, chemotaxis, and flagella formation were significantly inhibited. qRT-PCR quantification combined with the docking analysis demonstrated that AHPE affected the QS system of A. tumefaciens by repressing the transcriptional levels of traI and traR rather than signal mimicry. 1H NMR-based metabolic analysis indicated that the metabolism of A. tumefaciens was notably disturbed with AHPE treatment. AHPE treatment also resulted in the enhanced oxidative stress in A. tumefaciens. The enhanced oxidative stress lead to the disorder of energy supply, protein synthesis, and nucleotide metabolism, and ultimately attenuated the pathogenicity of A. tumefaciens. Our study indicated that AHPE can serve as a potential pesticide to defend against A. tumefaciens.

Down-regulation of Spinal 5-HT2A and 5-HT2C Receptors Contributes to Somatic Hyperalgesia induced by Orofacial Inflammation Combined with Stress.

Patients suffering with functional somatic pain syndromes such as temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS) have some similar symptoms, but the underlying cause is still unclear. The purpose of this study was to investigate whether 5-HT2A and 5-HT2C receptors in the spinal cord contribute to somatic hyperalgesia induced by orofacial inflammation combined with different modes of stress. Ovariectomized rats were injected subcutaneously with estradiol and bilateral masseter muscles were injected with complete Freund's adjuvant followed by stress. Somatic sensitivity was assessed with thermal and mechanical stimulation. The anxiety- and depression-like behaviors were measured by immobility time, sucrose preference, elevated plus maze and open field tests. The expression of 5-HT2A and 5-HT2C receptors in the spinal cord was examined by Western blot. Orofacial inflammation combined with 11 day forced swim stress (FSS) induced persistent mechanical allodynia for 15 days and thermal hyperalgesia for 2 days. The mechanical and thermal hyperalgesia lasted for 43 days and 30 days respectively following orofacial inflammation combined with 11 day heterotypic stress. Orofacial inflammation combined with stress induced anxiety- and depression-like behaviors. The expression of 5-HT2A and 5-HT2C receptors significantly decreased in the orofacial inflammation combined with stress groups. Intrathecal injection of 5-HT2A or 5-HT2C receptor agonist reversed somatic hyperalgesia. The results suggest that down-regulation of 5-HT2A and 5-HT2C receptors in the spinal cord contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress, indicating that 5-HT2A and 5-HT2C receptors may be potential targets in the treatment of TMD comorbid with FMS.

Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits.

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

Trametes orientalis polysaccharide alleviates PM2.5-induced lung injury in mice through its antioxidant and anti-inflammatory activities.

This paper examined the molecular conformation of Trametes orientalis polysaccharide (TOP-2) and evaluated the ameliorative effects of TOP-2 on PM2.5-induced lung injury in mice. The Congo red test and transmission electron microscopy (TEM) showed that TOP-2 had a triple-helical structure. PM2.5-induced pulmonary edema was ameliorated by TOP-2 intervention. PM2.5 notably increased the number of inflammatory cells and percentages of neutrophils in bronchoalveolar lavage fluid (BALF), and notably reduced the percentages of macrophages in BALF, while TOP-2 abolished these effects. The increased levels of total protein, albumin, C-reactive protein (CRP), myeloperoxidase (MPO), lactate dehydrogenase (LDH), alkaline phosphatase (AKP), acid sphingomyelinase (ASM), TNF-α, IL-1ß and IL-6 in BALF after PM2.5 exposure were inhibited by TOP-2. In addition, TOP-2 could not only remarkably promote the activities of antioxidant enzymes, but also reduce the levels of malondialdehyde (MDA), protein carbonyl group (PCG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Furthermore, TOP-2 up-regulated the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and inhibited the activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome in the lung tissue. These results hint that TOP-2 could alleviate PM2.5-induced lung injury in mice via its antioxidant and anti-inflammatory activities, and the underlying mechanisms, at least partly, depended on activation of the Nrf2/HO-1 pathway and inhibition of NLRP3 inflammasome.

C5aR1 promotes acute pyelonephritis induced by uropathogenic E. coli.

C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein. In addition to myeloid cells, C5aR1 is expressed on epithelial cells. In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role. We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC). This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice. Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium. In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling. Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.

Dissecting the behaviour of ß-amyloid peptide variants during oligomerization and fibrillation.

The oligomerization and fibrillation of ß-amyloid (Aß) peptides are important events in the pathogenesis of Alzheimer's disease. However, the motifs within the Aß sequence that contribute to oligomerization and fibrillation and the complex interplay among these short motifs are unclear. In this study, the oligomerization and fibrillation abilities of the Aß variants Aß1-28, Aß1-36, Aß11-42, Aß17-42, Aß1-40 and Aß1-42 were examined by thioflavin T fluorescence, western blotting and transmission electron microscopy. Compared with two C-terminal-truncated peptides (i.e. Aß1-28 and Aß1-36), Aß11-42, Aß17-42 and Aß1-42 had stronger abilities to form oligomers. This indicated that amino acids 37-42 strengthen the ß-hairpin structure of Aß. Both Aß1-42 and Aß1-40 could form fibres, but Aß17-42 formed irregular fibres, suggesting that amino acids 1-17 were essential for Aß fibre formation. Aß1-28 and Aß1-36 exhibited weak oligomerization and fibrillation, implying that they formed an unstable ß-hairpin structure owing to the incomplete C-terminal region. Intermediate peptides were likely to form a stable structure, consistent with previous results. This work explains the roles and interplay among motifs within Aß during oligomerization and fibrillation. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Bis(sulfosuccinimidyl) suberate (BS3) crosslinking analysis of the behavior of amyloid-ß peptide in solution and in phospholipid membranes.

The structure and state of amyloid-ß peptide (Aß) oligomers often need to be checked by reliable experimental methods. Electrophoresis is a commonly applied measurement method. However, due to the presence of detergents, oligomers are easily broken during electrophoresis, which makes it very hard to accurately assess Aß aggregate states. In the current study, bis(sulfosuccinimidyl) suberate (BS3) was used to cross-link Aß1-42 oligomers prior to electrophoresis. When compared to a previously reported Aß cross-linking agent, glutaraldehyde, it was quite apparent that BS3 is more suitable for detecting intra-membrane Aß oligomers and extra-membrane Aß oligomers states. As such, our findings provide an efficient method for analyzing Aß proteins or other proteins that are easily aggregated in solution and in phospholipid membranes.

Minimally Modified LDL-Induced Impairment of Endothelium-Dependent Relaxation in Small Mesenteric Arteries of Mice.

Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultramicrostructure of mesenteric vascular beds was investigated using a transmission electron microscope. The results showed that mmLDL significantly impaired the acetylcholine-induced (3 × 10-10 to 1 × 10-4M) endothelium-dependent relaxation of mouse mesenteric arteries with markedly reduced pIC50 (p < 0.05) and Rmax values (p < 0.001). In addition, mmLDL increased the levels of superoxide production and nitrotyrosine concentration and impaired the endothelial microstructure with decreased KCa3.1 and KCa2.3 expression. In conclusion, mmLDL increases superoxide and nitrotyrosine levels, damages endothelial microstructure with decreased KCa3.1 and KCa2.3 expression, and ultimately attenuates relaxation mediated by nitric oxide- and endothelium-derived hyperpolarizing factor.

The ERK1/2 pathway participates in the upregulation of the expression of mesenteric artery α1 receptors by intravenous tail injections of mmLDL in mice.

Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular diseases. However, no studies examining the effect of mmLDL on vascular smooth muscle receptors have been released. The current study investigated the effect of mmLDL on the mesenteric artery α1 adrenoceptor and the molecular mechanisms. Mice were divided into the normal saline (NS), mmLDL, and mmLDL+U0126 groups. In the mmLDL+U0126 group, the animals were subjected to an intravenous tail injection of mmLDL and an intraperitoneal injection of U0126. Vascular tension caused by noradrenaline (NA) in mesenteric arteries was measured with a sensitive myograph system. The serum levels of oxLDL, TNF-α, and IL-1ß were detected using enzyme-linked immunosorbent assays. The expressions of the α1 adrenoceptor, the α2 adrenoceptor, TNF-α, IL-1ß, and pERK1/2 were detected using real-time polymerase chain reactions and Western blot analysis. Compared with the NS group, the mmLDL group exhibited a noticeably enhanced NA shrinkage dose-response curve and a significantly increased Emax value (P<0.01). Prazosin (α1 adrenoceptor antagonist) caused a noticeable right shift of the dose-response curve. U0126 inhibited the increases in the serum levels and vessel wall expression of IL-1ß and TNF-α and enhanced the NA shrinkage dose-response curve caused by mmLDL, as observed by a significantly decreased Emax value (P<0.01). It inhibited the increased α1 adrenoceptor expression caused by mmLDL. The serum levels of IL-1ß and TNF-α demonstrated a positive correlation with the NA-induced maximum shrinkage percentage. U0126 inhibited the mmLDL-induced increase in the pERK1/2 protein level in the vessel wall. In conclusion, mmLDL increased the serum levels of IL-1ß and TNF-α in vivo by activating the ERK1/2 pathway, which resulted in α1 receptor-mediated vasoconstriction and an increase in the expression of α1 adrenoceptor. The results of this study may provide new ideas for the prevention and cure of cardiovascular diseases in the future.

Activation of PPAR alpha by fenofibrate inhibits apoptosis in vascular adventitial fibroblasts partly through SIRT1-mediated deacetylation of FoxO1.

Recent studies demonstrated that the ligand-activated transcription factor peroxisome proliferator-activated receptorα (PPARα) acts in association with histone deacetylase sirtuin 1 (SIRT1) in the regulation of metabolism and inflammation involved in cardiovascular diseases. PPARα activation also participates in the modulation of cell apoptosis. Our previous study found that SIRT1 inhibits the apoptosis of vascular adventitial fibroblasts (VAFs). However, whether the role of PPARα in apoptosis of VAFs is mediated by SIRT1 remains unknown. In this study, we aimed to determine the effect of PPARα agonist fenofibrate on cell apoptosis and SIRT1 expression and related mechanisms in ApoE(-/-) mice and VAFs in vitro. We found that fenofibrate inhibited cell apoptosis in vascular adventitia and up-regulated SIRT1 expression in aorta of ApoE(-/-) mice. Moreover, SIRT1 activator resveratrol (RSV) further enhanced these effects of fenofibrate. In vitro study showed that activation of PPARα by fenofibrate inhibited TNF-α-induced cell apoptosis and cell cycle arrest in VAFs. Meanwhile, fenofibrate up-regulated SIRT1 expression and inhibited SIRT1 translocation from nucleus to cytoplasm in VAFs stimulated with TNF-α. Moreover, the effects of fenofibrate on cell apoptosis and SIRT1 expression in VAFs were reversed by PPARα antagonist GW6471. Importantly, treatment of VAFs with SIRT1 siRNA or pcDNA3.1(+)-SIRT1 showed that the inhibitory effect of fenofibrate on cell apoptosis in VAFs through SIRT1. On the other hand, knockdown of FoxO1 decreased cell apoptosis of VAFs compared with fenofibrate group. Overexpression of FoxO1 increased cell apoptosis of VAFs compared with fenofibrate group. Further study found that fenofibrate decreased the expression of acetylated-FoxO1 in TNF-α-stimulated VAFs, which was abolished by SIRT1 knockdown. Taken together, these findings indicate that activation of PPARα by fenofibrate inhibits cell apoptosis in VAFs partly through the SIRT1-mediated deacetylation of FoxO1.

Activation of endogenous anti-inflammatory mediator cyclic AMP attenuates acute pyelonephritis in mice induced by uropathogenic Escherichia coli.

The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells.

Comparison of entecavir and adefovir for the treatment of chronic hepatitis B.

The results of several new clinical trials that compared the effectiveness of entecavir (ETV) treatment with that of adefovir (ADV) treatment in patients with chronic hepatitis B (CHB) were published in recent years. However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion as to whether ETV is more effective than ADV. Therefore, a new meta-analysis was needed to compare ETV with ADV for the treatment of CHB. A search of the Cochrane Central Register of Controlled Trials (CCTR), MEDLINE, the Science Citation Index, Embase, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database for relevant studies published between 1966 and 2010 was performed. Trials comparing the use of ETV and ADV for the treatment of CHB were assessed. Of the 2,358 studies screened, 13 randomized controlled clinical trials comprising 1,230 patients (ETV therapy, 621; ADV therapy, 609) were analyzed. The serum hepatitis B virus (HBV) DNA clearance rate obtained in patients treated with ETV was significantly higher than that in patients treated with ADV at the 24th and 48th weeks of treatment (24 weeks: 59.6% vs. 31.8%, relative risk [RR], 1.82, 95% CI: 1.49-2.23; 48 weeks: 78.3% vs. 50.4%, RR, 1.61, 95% CI: 1.32-1.96). The serum HBeAg clearance rate, the HBeAg seroconversion rate, and the ALT normalization rate obtained for patients treated with ETV were also higher than the corresponding values for patients treated with ADV at the 48th week of treatment. The safety profiles were similar between patients treated with ETV and those treated with ADV. The evidence reviewed in this meta-analysis suggests that patients with hepatitis B have a greater likelihood of achieving a viral response and a biomedical response when treated with ETV than when treated with ADV.

Comparison of entecavir and adefovir for the treatment of chronic hepatitis B

The results of several new clinical trials that compared the effectiveness of entecavir (ETV) treatment with that of adefovir (ADV) treatment in patients with chronic hepatitis B (CHB) were published in recent years. However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion as to whether ETV is more effective than ADV. Therefore, a new meta-analysis was needed to compare ETV with ADV for the treatment of CHB. A search of the Cochrane Central Register of Controlled Trials (CCTR), MEDLINE, the Science Citation Index, Embase, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database for relevant studies published between 1966 and 2010 was performed. Trials comparing the use of ETV and ADV for the treatment of CHB were assessed. Of the 2,358 studies screened, 13 randomized controlled clinical trials comprising 1,230 patients (ETV therapy, 621; ADV therapy, 609) were analyzed. The serum hepatitis B virus (HBV) DNA clearance rate obtained in patients treated with ETV was significantly higher than that in patients treated with ADV at the 24th and 48th weeks of treatment (24 weeks: 59.6% vs. 31.8%, relative risk [RR], 1.82, 95% CI: 1.49-2.23; 48 weeks: 78.3% vs. 50.4%, RR, 1.61, 95% CI: 1.32-1.96). The serum HBeAg clearance rate, the HBeAg seroconversion rate, and the ALT normalization rate obtained for patients treated with ETV were also higher than the corresponding values for patients treated with ADV at the 48th week of treatment. The safety profiles were similar between patients treated with ETV and those treated with ADV. The evidence reviewed in this meta-analysis suggests that patients with hepatitis B have a greater likelihood of achieving a viral response and a biomedical response when treated with ETV than when treated with ADV.

Association between TaqIB polymorphism of cholesteryl ester transfer protein and coronary artery disease in the Chinese population.

OBJECTIVE: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. METHODS: We searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: The literature search yielded 448 studies, in which 10 case-control studies including 1694 cases and 1456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89-1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09-1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers. CONCLUSIONS: In the present study, the TaqIB polymorphism of CETP was found to be associated with CAD in the Chinese population.

Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced hepatocarcinogenesis: involvement of CCAAT/enhancer binding protein ß and cyclooxygenase-2.

Cyclooxygenase-2 (COX-2) and CCAAT/enhancer binding protein ß (C/EBPß) have been shown to be involved in inflammation and carcinogenesis, and our previous study revealed that they were co-overexpressed in human hepatocellular carcinoma (HCC) tissue and a positive correlation was found. Saikosaponin-d (SSD), a triterpene saponin extracted from Bupleurum falcatum L. (Umbelliferae), is known to exert inhibitory effects on COX-2 expression, together with inflammation and hepatic fibrosis. These findings prompted us to investigate the chemopreventive potential of SSD against hepatocarcinogenesis and its possible molecular mechanism in vivo. An experimental model with diethylinitrosamine (DEN)-treated Sprague Dawley rats was used in the present study. DEN (50 mg/kg body weight) and SSD (2 mg/kg body weight) were intraperitoneally injected weekly and daily, respectively. Administration of SSD alone had no side effects. The liver nodule formation, tumorous invasion to surrounding organs and increased cellular atypia induced by DEN were markedly reduced by SSD in the SSD + DEN group compared with the DEN group. On the other hand, immunohistochemical staining demonstrated that the expression of COX-2 and C/EBPß proteins was significantly increased in tumor cells and macrophages of liver tissue from DEN-treated rats, whereas the expression of the two proteins was markedly lowered in the SSD + DEN group. Overall, our results suggest that SSD prevents DEN-induced hepatocarcinogenesis in rats through inhibition of C/EBPß and COX-2, providing indispensable experimental evidence for the clinical application of SSD as a novel chemopreventive agent against HCC in the future.