Gene expression profiling in fetal rat lung during gestational perfluorooctane sulfonate exposure

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in the tissues of humans and wildlife. It has been reported that gestational exposure to PFOS causes neonatal death of rats. However, the mechanism is still unclear. In this study, we investigated the effects of gestational PFOS exposure on the gene expression profiling of fetal rat lung at pseudoglandular stage. Adult Sprague Dawley dams were dosed orally from gestational day 12-18 with 0 (control), 5 mg/kg/day or 20 mg/kg/day PFOS. Animals were euthanized on day 18.5, fetal lung samples were collected for histochemical staining and RNA profiling analysis. PFOS did not cause apparent microscopic changes of fetal lungs. Gene expression profiling revealed that PFOS dose-dependently up-regulated the expression of 21 (5 mg/kg) and 43 (20 mg/kg) genes. These genes include five PPARα target genes (Acot1, Hmgcs2, Fabp4, Fabp1 and Myh7), and 4 of them are involved in lipid metabolism. The other genes were primarily included in the categories of cytoskeletal structure (Tpm1, Tnnt2, Actn3, Myoz2, Tmod1, and Mfap5), extracellular matrix (Ckm, Lum, Tnnc1, Art3, Dcn, Col17a1, Aspn, Ctsk, Itm2a, Spock2 and Orm1), transporting (Cox8h, Cox6a2 and Scnn1a) and secreted proteins (Scgb3a1, Nppb and Spp1). Our study demonstrates that in utero PFOS exposure resulted in the alteration of a set of genes which are involved in significant cytoskeletal, extracellular matrix remodeling, lipid metabolism and secreted proteins in the fetal rat lung.     

PKCα regulates vasopressin-induced aquaporin-2 trafficking in mouse kidney collecting duct cells in vitro via altering microtubule assembly

Aim:

Aquaporin-2 (AQP2) is a vasopressin-regulated water channel located in the collecting tubule and collecting duct cells of mammalian kidney. The aim of this study is to investigate whether PKCα plays a role in vasopressin-induced AQP2 trafficking in mouse inner medullary collecting duct 3 (mIMCD3) cells.

Methods:

AQP2-mIMCD3 stable cell line was constructed by transfection of mouse inner medullary collecting duct 3 (mIMCD3) cells with AQP2-GFP construct. Then the cells were transfected with PKCα shRNA, PKCα A/25E, or PKCα scrambled shRNA. The expression levels of PKCα, AQP2, and phospho-S256-AQP2 were analyzed using Western blot. The interaction between AQP2 and PKCα was examined using immunoprecipitation. The distribution of AQP2 and microtubules was studied using immunocytochemistry. The AQP2 trafficking was examined using the biotinylation of surface membranes.

Results:

Treatment of AQP2-mIMCD3 cells with 100 μmol/L of 1-desamino-8-D-arginine vasopressin (DdAVP) for 30 min stimulated the translocation of AQP2 from the cytoplasm to plasma membrane through influencing the microtubule assembly. Upregulation of active PKCα by transfection with PKCα A/25E plasmids resulted in de-polymerization of α-tubulin and redistributed AQP2 in the cytoplasm. Down-regulation of PKCα by PKCα shRNA partially inhibited DdAVP-stimulated AQP2 trafficking without altering α-tubulin distribution. Although 100 μmol/L of DdAVP increased AQP2 phosphorylation at serine 256, down-regulation of PKCα by PKCα shRNA did not influence DdAVP-induced AQP2 phosphorylation, suggesting that AQP2 phosphorylation at serine 256 was independent of PKCα. Moreover, PKCα did not physically interact with AQP2 in the presence or absence of DdAVP.

Conclusion:

Our results suggested that PKCα regulates AQP2 trafficking induced by DdAVP via microtubule assembly.     

Improving the cardio protective effect of aFGF in ischemic myocardium with ultrasound-mediated cavitation of heparin modified microbubbles: preliminary experiment

Ultrasound (US)-mediated cavitation of microbubbles has evolved into a new tool for organ-specific gene and drug delivery. This paper was to investigate the feasibility of acidic fibroblast growth factor (aFGF) intravenous delivery to the ischemic myocardium of rats by ultrasonic microbubbles modified with heparin. Heparin modified microbubbles (HMB) were prepared by the freeze-dried method. Acute myocardial infarction (AMI) model was established and the cardio protective effect of the aFGF combing with HMB (aFGF-HMB) under US-mediated cavitation technique was investigated. aFGF-HMB combined with US-mediated cavitation technique was examined by ECG. Ejection fraction (EF), fractional shortening (FS) and left ventricular diastolic diameter (LVDd) were measured to monitor the improvement of global myocardial contractile function. Myocardial tissue was stained with hematoxylin and eosine (HE) to evaluate the elaborate general morphology of the ischemic myocardium. From morphologic observation and echocardiography in rat heart, aFGF-HMB had suitable size distribution, physical stability and good acoustic resonance function. From AMI rat experiments, aFGF-HMB under US-mediated cavitation technique exerted aFGF cardio protective effect in ischemic myocardium. From histological evaluation, US-mediated cavitation of aFGF-HMB showed improvement of myocardial ischemia. With the visual imaging and US-triggered drug release advantages, US-mediated cavitation of aFGF-HMB might be developed as a novel technique for targeting delivery of aFGF into ischemic myocardium.     

Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers

A placebo controlled, randomised, double blind trial was conducted in human volunteers to test a mixture of three recombinant Plasmodium falciparum blood stage antigens for its ability to reduce the initial growth rates of parasites. The vaccine contained recombinant MSP2 (3D7 allele), a portion of MSP1 (190LCS.T3) and part of the RESA antigen (C terminal 771 amino acids) in the Montanide ISA 720 adjuvant (SEPPIC). Twelve volunteers received two doses of the vaccine, 6 weeks apart. The five participants in the placebo group received an equivalent volume of the adjuvant emulsion using the same schedule. Antibody responses were low, as has been reported in earlier studies with this combination, while T cell responses were stronger. All the volunteers were challenged with approximately 140 ring infected red cells of the 3D7 cloned line, 4 weeks after the second dose. Parasitaemia was determined once daily from day 4 using a sensitive and quantitative PCR assay. All the volunteers were infected and were treated on day 8, before any developed symptoms. There was no significant difference in initial parasite growth rates between the verum and placebo groups, nor was there any significant correlation between parasite growth rates and any of the measured immunological responses. These results suggest that the formulation tested in this trial did not generate immune responses that were strong enough to reduce parasite growth in naive volunteers.     

Four butenolides are novel cytotoxic compounds isolated from the marine-derived bacterium,Streptoverticillium luteoverticillatum 11014

Four known butenolides were isolated from the ethyl acetate extracts of the culture broth of the marine-derived bacterium, Streptoverticillium luteoverticillatum, by bioassay-guided fractionation. The structures were identified on the basis of spectral data. The absolute configuration of compound (1) was determined by CD spectrum for the first time. Compounds 1-4 showed in vitro cytotoxicity against the murine lymphoma P388 and human leukemia K562 cell lines. This is the first report on the isolation of butenolides from the marine bacterium, Streptoverticillium luteoverticillatum, and their cytotoxic activities.     

手工Q版冰皮月饼

【月饼馅的制作方法】原料红豆250克,白芸豆250克,白糖30克,红糖50克,糖桂花20克,色拉油40克(无味)制作1将红豆泡发好,放进电高压锅,倒入高出红豆约6厘米的清水,盖上锅盖高压30分钟(白芸豆也用此法,放水量没有限制,但压的时间要长一些)。2准备一碗清水,放入压好的红豆,用手反复搓揉红豆。3拿一个放置漏网的碗,把搓好的红豆倒在漏网上,过滤出红豆皮。     

江苏省男男性行为人群性传播疾病感染状况及危险因素

目的 分析江苏省男男性行为人群梅毒、淋球菌和沙眼衣原体感染状况及其相关危险因素.方法 采用滚雪球法于2010年8-10月在江苏省常州市和扬州市选取400名男男性行为者(MSM)进行现场问卷调查,共获得328份既采集静脉血又采集直肠拭子的有效对象.对静脉血使用ELISA法和甲苯胺红不加热血清试验(TRUST)进行梅毒螺旋体检测,对采集的直肠拭子进行淋球菌和沙眼衣原体的检测.采用logistic回归分析梅毒螺旋体、淋球菌和沙眼衣原体感染的影响因素.结果 328名调查对象年龄为(32.46 +9.72)岁,未婚者占59.15％ (194/328);75.00％ (246/328)的调查对象最近3个月与男性发生过肛交行为,最近1次肛交时使用安全套的比率为56.71％(186/328),53.05％ (174/328)的调查对象在最近3个月内未与女性发生过性行为.梅毒的现症感染率为13.41％ (44/328),淋球菌的感染率为3.66％( 12/328),沙眼衣原体的感染率为11.59％( 38/328).有1～2名男性性伴者的梅毒感染率为7.55％ (8/106),有3名及以上男性性伴者的梅毒感染率为25.81％ (16/62).男性性伴数越多感染梅毒的危险性就越大(OR =4.213,95％ CI:1.133～15.656).结论 江苏省部分城市MSM人群梅毒和沙眼衣原体感染率高,高危性行为发生率高,应加强对MSM高危行为的干预.     

Physical activity, cardiorespiratory fitness, and obesity among Chinese children

Objective

To investigate the relationships of cardiorespiratory fitness (CRF) and physical activity (PA) with the risk of overweight/obesity in Chinese schoolchildren.

Methods

A total of 1795 children aged 8-13 years at baseline were followed-up for 18 months from 2006 to 2008 in Guangzhou, China. Children were categorized as “normal weight”, “overweight”, and “obese” using Chinese obesity cut-off points. Data on self-reported PA were obtained. CRF was determined by the 20-meter multistage fitness test, and the sex-specific median values were set as the cut-off points for the classification of high and low CRF.

Results

Significantly higher CRF was found in children with normal weight (from 6.55 to 8.65 ml/kg/min) or physically active children (from 0.42 to 1.22 ml/kg/min) compared with the reference group. CRF was inversely associated with the kg/m² change in BMI during the follow-up period (β = − 0.63 kg/m² and − 0.64 kg/m² for boys and girls, respectively, both p < 0.001). Significant association of baseline CRF with overweight/obesity was found in boys (odds ratio (OR) 8.71; 95% confidence interval (CI) 2.59-29.26, p < 0.001), whereas the association was marginally insignificant in girls (OR 6.87; 95% CI 0.96-49.09, p = 0.055).

Conclusions

The results showed a strong negative association between CRF levels and children's BMI and weight gain.     

The characteristic of codon usage pattern and its evolution of hepatitis C virus

To give a new perspective on the codon usage of the hepatitis C virus (HCV) and the factors accounting for shaping the codon usage pattern of the virus, the relative synonymous codon usage (RSCU) values, aromaticity and hydrophobicity of each polyprotein of the virus, effective number of codons (ENC) values and nucleotide contents were calculated to implement a comparative analysis to evaluate the dynamics of the virus evolution. The RSCU values of each codon of 144 HCV ORFs indicated that all abundant codons were C/G-ended codons. The plots of principal component analysis based on sub-genotype of HCV indicated that sub-genotype 1a and 1b separated clearly on the axis of f2 suggesting that the codon usage bias between sub-genotype 1a and 1b strains was different. By comparing the codon usage between HCV and human cells, we found that the synonymous codon usage pattern of HCV was a mixture of coincidence and antagonism to that of host cells. The characteristics of the synonymous codon usage patterns and nucleotide contents of HCV, and the correlation analysis between GC(3s), GC(1,2s), GC% (ORF), GC% (5'-UTR), GC% (3'-UTR), aromaticity, hydrophobicity and ENC value, respectively, indicated that mutational pressure was the dominant factor accounting for the codon usage variation and selection pressure also accounted for HCV codon usage pattern.     

Milk consumption and bladder cancer risk: a meta-analysis of published epidemiological studies

Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of milk intake using fixed- or random-effect models depending on the heterogeneity of effects among studies. Nineteen cohort and case-control studies were eligible for inclusion. High milk intake was significantly associated with decreased risk of bladder cancer (OR, 0.84; 95% CI, 0.71-0.97) when comparing the highest with the lowest category of milk intake. The inverse association was stronger in Asia (OR, 0.60; 95% CI, 0.40-0.81) than North America (OR, 0.89; 95% CI, 0.76-1.03), and no association was observed in Europe (OR, 1.05; 95% CI, 0.85-1.26). This relationship also varied significantly by specific dairy products. Our results suggest that milk may be related to the reduction of bladder cancer risk. Further studies need to clarify the biological mechanisms.