The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Inhibition of hyperpolarization-activated cyclic nucleotide-gated cation channel attenuates cerebral ischemia reperfusion-induced impairment of learning and memory by regulating apoptotic pathway.

Stroke is the second leading cause of death globally. Cognitive dysfunction is a common complication of stroke, which seriously affects the patient's quality of life. Previous studies have shown that the expression of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel is closely related to ischemia-reperfusion (IR) injury and subsequent cognitive impairment. We also found that ZD7288, a specific inhibitor of the HCN channel, attenuated IR injury during short-term reperfusion. Since apoptosis can induce cell necrosis and aggravate cognitive impairment after IR, the purpose of this study is to define whether ZD7288 could improve cognitive impairment after prolonged cerebral reperfusion in rats by regulating apoptotic pathways. Our data indicated that ZD7288 can ameliorate spatial cognitive behavior and synaptic plasticity, protect the morphology of hippocampal neurons, and alleviate hippocampal apoptotic cells in IR rats. This effect may be related to down-regulating the expressions of pro-apoptotic proteins such as AIF, p53, Bax, and Caspase-3, and increasing the ratio of Bcl-2/Bax. Taken together, it suggested that inhibition of the HCN channel improves cognitive impairment after IR correlated with its regulation of apoptotic pathways.

Clonidine ameliorates cerebral ischemia-reperfusion injury by up-regulating the GluN3 subunits of NMDA receptor.

This study aimed to investigate the protective effects of the alpha-2 adrenergic receptor (α2-AR) agonist, clonidine, on the cerebral ischemia-reperfusion (I/R) injury and elaborate the underlying mechanisms. Cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 4 h in adult male SD rats. Saline, clonidine and yohimbine (an α2-AR antagonist) were intraperitoneally administered each day for one week before surgery. Neurological deficit was evaluated just before decapitation. TTC staining was applied for correlation of cerebral infarction volume. HE staining was performed to observe the neuron morphology. Immunohistochemical staining was performed to detect the localization and expression of GluN3 proteins. Western blot analysis also was used to detect the expression levels of GluN3 proteins. Our data showed that clonidine ameliorated neurological deficit and reduced the cerebral infarction volume of the rats with cerebral I/R. It is worth noting that treatment with clonidine up-regulated the protein expression of GluN3 in the rats with the cerebral I/R, especially in the cell membrane. Moreover, clonidine also up-regulated the transposition from cytoplasm to cell membrane of GluN3 after cerebral I/R. In addition, yohimbine abolished the neuroprotective effects of clonidine. The results indicated that clonidine played a protective role in cerebral I/R injury through regulation of the protein expression of GluN3 subunits of N-methyl-D-aspartate (NMDA) receptor.

Increased intracellular Cl- concentration mediates neutrophil extracellular traps formation in atherosclerotic cardiovascular diseases.

Neutrophil extracellular traps (NETs) play crucial roles in atherosclerotic cardiovascular diseases such as acute coronary syndrome (ACS). Our preliminary study shows that oxidized low-density lipoprotein (oxLDL)-induced NET formation is accompanied by an elevated intracellular Cl- concentration ([Cl-]i) and reduced cystic fibrosis transmembrane conductance regulator (CFTR) expression in freshly isolated human blood neutrophils. Herein we investigated whether and how [Cl-]i regulated NET formation in vitro and in vivo. We showed that neutrophil [Cl-]i and NET levels were increased in global CFTR null (Cftr-/-) mice in the resting state, which was mimicked by intravenous injection of the CFTR inhibitor, CFTRinh-172, in wild-type mice. OxLDL-induced NET formation was aggravated by defective CFTR function. Clamping [Cl-]i at high levels directly triggered NET formation. Furthermore, we demonstrated that increased [Cl-]i by CFTRinh-172 or CFTR knockout increased the phosphorylation of serum- and glucocorticoid-inducible protein kinase 1 (SGK1) and generation of intracellular reactive oxygen species in neutrophils, and promoted oxLDL-induced NET formation and pro-inflammatory cytokine production. Consistently, peripheral blood samples obtained from atherosclerotic ApoE-/- mice or stable angina (SA) and ST-elevation ACS (STE-ACS) patients exhibited increased neutrophil [Cl-]i and SGK1 activity, decreased CFTR expression, and elevated NET levels. VX-661, a CFTR corrector, reduced the NET formation in the peripheral blood sample obtained from oxLDL-injected mice, ApoE-/- atherosclerotic mice or patients with STE-ACS by lowering neutrophil [Cl-]i. These results demonstrate that elevated neutrophil [Cl-]i during the development of atherosclerosis and ACS contributes to increased NET formation via Cl--sensitive SGK1 signaling, suggesting that defective CFTR function might be a novel therapeutic target for atherosclerotic cardiovascular diseases.

Platelet CFTR inhibition enhances arterial thrombosis via increasing intracellular Cl- concentration and activation of SGK1 signaling pathway.

Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl- levels ([Cl-]i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl-]i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl-]i was increased in platelets from CAD patients. In a FeCl3-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased platelet [Cl-]i, which accelerated thrombus formation, enhanced platelet aggregation and ATP release, and increased P2Y12 and PAR4 expression in platelets. Conversely, Cftr-overexpressing platelets resulted in subnormal [Cl-]i, thereby decreasing thrombosis formation. Our results showed that clamping [Cl-]i at high levels or Cftr deficiency-induced [Cl-]i increasement dramatically augmented phosphorylation (Ser422) of serum and glucocorticoid-regulated kinase (SGK1), subsequently upregulated P2Y12 and PAR4 expression via NF-κB signaling. Constitutively active mutant S422D SGK1 markedly increased P2Y12 and PAR4 expression. The specific SGK1 inhibitor GSK-650394 decreased platelet aggregation in wildtype and platelet-specific Cftr knockout mice, and platelet SGK1 phosphorylation was observed in line with increased [Cl-]i and decreased CFTR expression in CAD patients. Co-transfection of S422D SGK1 and adenovirus-induced CFTR overexpression in MEG-01 cells restored platelet activation signaling cascade. Our results suggest that [Cl-]i is a novel positive regulator of platelet activation and arterial thrombus formation via the activation of a [Cl-]i-sensitive SGK1 signaling pathway. Therefore, [Cl-]i in platelets is a novel potential biomarker for platelet hyperactivity, and CFTR may be a potential therapeutic target for platelet activation in CAD.

Antiplatelet and Antithrombotic Effects of Isaridin E Isolated from the Marine-Derived Fungus via Downregulating the PI3K/Akt Signaling Pathway.

Isaridin E, a cyclodepsipeptide isolated from the marine-derived fungus Amphichorda felina (syn. Beauveria felina) SYSU-MS7908, has been demonstrated to possess anti-inflammatory and insecticidal activities. Here, we first found that isaridin E concentration-dependently inhibited ADP-induced platelet aggregation, activation, and secretion in vitro, but did not affect collagen- or thrombin-induced platelet aggregation. Furthermore, isaridin E dose-dependently reduced thrombosis formation in an FeCl3-induced mouse carotid model without increasing the bleeding time. Mechanistically, isaridin E significantly decreased the ADP-mediated phosphorylation of PI3K and Akt. In conclusion, these results suggest that isaridin E exerts potent antithrombotic effects in vivo without increasing the risk of bleeding, which may be due to its important role in inhibiting ADP-induced platelet activation, secretion and aggregation via the PI3K/Akt pathways.

Fibroblast Growth Factor 21 Exerts its Anti-inflammatory Effects on Multiple Cell Types of Adipose Tissue in Obesity.

OBJECTIVE: Obesity-related, chronic, low-grade inflammation has been identified as a key factor in the development of many metabolic diseases, such as type 2 diabetes and cardiovascular diseases. Adipocytes, preadipocytes, and macrophages have been implicated in initiating inflammation in adipose tissue. This study aims to investigate the effects of fibroblast growth factor-21 (FGF-21) on obesity-related inflammation and its mechanisms in vivo and in vitro. METHODS: Monosodium glutamate (MSG) was used to induce obesity in mice and subsequently treated the mice with or without FGF-21. Primary adipocytes and stromal vascular fraction cells were isolated from MSG-obesity mice for additional experiments. RESULTS: Results obtained by ELISA and real-time polymerase chain reaction showed that FGF-21 efficiently ameliorated obesity-related inflammation in MSG-obesity mice. This study demonstrated that preadipocytes and adipocytes responded to anti-inflammatory effects of FGF-21. In vitro, 3 T3-L1 preadipocytes lacking ß-klotho did not respond to FGF-21 under glucose uptake. Interestingly, the treatment of 3 T3-L1 preadipocytes with FGF-21 significantly attenuated lipopolysaccharide-induced inflammatory response. CONCLUSIONS: Our study showed that FGF-21-induced glucose uptake and FGF-21-related anti-inflammatory effects are mediated by different signaling pathways. Moreover, FGF-21 showed anti-inflammatory effects on preadipocytes; these effects are mediated by the fibroblast growth factor receptor substrate 2/ERK1/2 signaling pathway.

Ribosomal protein L7 as a suitable reference gene for quantifying gene expression in gastropod Bellamya aeruginosa.

Expression levels of eight candidate reference genes were quantified in tissues of gastropod Bellamya aeruginosa exposed for 10 d to various stressors, including fasting, 17ß-estradiol, 17α-methyltestosterone, and Cd(2+). The results showed that 18s rRNA was the most highly expressed of the candidate reference genes, while H2A was the least expressed. There were no significant changes (p>0.05) in the expression of the eight genes in tissues among the different treatments. Using RefFinder to evaluate the expression stabilities of the eight candidate reference genes, ribosomal protein was shown to be the most stable reference gene, and no effects were observed among the different stressor treatments. These results indicate that RPL 7 is the most suitable reference gene for quantifying gene expression in B. aeruginosa under environmental stress, which was verified in B. aeruginosa exposed to high doses of E2 for 24 and 72h.

Synthesis and quantitative structure-activity relationships study for phenylpropenamide derivatives as inhibitors of hepatitis B virus replication.

A series of new phenylpropenamide derivatives containing different substituents was synthesized, characterized and evaluated for their anti-hepatitis B virus (HBV) activities. The quantitative structure-activity relationships (QSAR) of phenylpropenamide compound have been studied. The 2D-QSAR models, based on DFT and multiple linear regression analysis methods, revealed that higher values of total energy (TE) and lower entropy (S(Ó©)) enhanced the anti-HBV activities of the phenylpropenamide molecules. Predictive 3D-QSAR models were established using SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.

Anti-apoptotic potency of TNFR:Fc gene in ischemia/ reperfusion-induced myocardial cell injury.

The aim of the study was to investigate the anti-apoptotic potency of TNFR:Fc gene in ischemia/reperfusion-induced myocardial cell injury and hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes injury. Rats were randomly divided into the following groups (n=8): (1) sham operation group; (2) ischemia-reperfusion (I/R) rats treated with rAAV-EGFP; (3) I/R rats treated with rAAV-TNFR:Fc group. rAAV-EGFP or rAAV-TNFR:Fc was injected intra-myocardial at four sites on the anterior and posterior walls of left ventricle immediately after the construction of I/R-induced AMI model in rats. The effects of TNFR:Fc on apoptosis and cardiacfunction were observed after 72 h of coronary reperfusion. In the in vitro study, apoptosis was analyzed in H9c2 rat cardiomyocytes treated either with nomoxia alone, or hypoxia/reoxygenation in the presence of rAAV-GFP or rAAV-TNFR:Fc. We found that (1) TNFR:Fc gene improved cardiac function (EF, LVESP, LVEDP and dp/dt max) post I/R-induced AMI; (2) TNFR:Fc gene inhibited I/R-induced apoptosis and attenuated the level of TNF-α in serum and cardiac tissue; (3) TNFR:Fc gene prevented apoptosis in hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes associated with inhibition of caspase-3 activation and normalization of ratio of the Bcl-2/Bax. We concluded that TNFR:Fc gene transfection has anti-apoptotic potency in ischemia/reperfusion-induced myocardial cell injury.

The association between B vitamins supplementation and adverse cardiovascular events: a meta-analysis.

This study is to explore the association of adverse cardiovascular events with B vitamins supplementation. Rev.Man 5.1 and Stata 11.0 software were applied for the meta-analysis. The number of cardiovascular events was collected and calculated using indicates of odds ratio and 95% confidence intervals in a fixed-effects or a random-effects model when appropriate. The study includes 15 studies which consists of 37,358 study objects (experimental group: 19,601; control group: 17,757). This study showed that the pooled ORs was 1.01 (95% CI = 0.96~1.06, P > 0.05) for objects with Experimental group (B vitamins supplementation) vs. Control group (placebo or regular treatment), which suggests no significant differences were found in the overall effect of the number of cardiovascular events between the two groups. Further stratification of subgroup analysis indicates no significant differences were found between the two groups as well. There were also no publication bias existing by the Egger's linear regression test (P > 0.05). Our result indicates that the number of cardiovascular events in experimental group using B vitamins supplementation during the treatment is equal to placebo or regular treatment group thus further studies is necessary.

Insulin-like growth factor 1 treatment of MSCs attenuates inflammation and cardiac dysfunction following MI.

It has been reported that insulin-like growth factor 1 (IGF-1) promoted migration of endothelial cells and cardiac resident progenitor cells. In the previous study, we found the time-dependent and dose-dependent effects of IGF-1 treatment on the CXCR4 expression in MSCs in vitro, but it is still not clear whether IGF-1 pretreatment of MSCs may play anti-apoptotic and anti-inflammation role in myocardial infarction. In this study, we demonstrated that IGF-1-treated MSCs' transplantation attenuate cardiac dysfunction, increase the survival of engrafted cells in the ischemic heart, decrease myocardium cells apoptosis, and inhibit protein production and gene expression of inflammation cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6. IGF-1 pretreatment of MSCs may play anti-apoptotic and anti-inflammation roles in post-myocardial infarction.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

CHADS2 versus CHA2DS2-VASc score in assessing the stroke and thromboembolism risk stratification in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of the predictive abilities of CHADS2 and CHA2DS2-VASc in stroke and thromboembolism risk stratification of atrial fibrillation (AF) patients. METHODS: We searched PubMed and EMBASE for English-language literature on comparisons of the diagnostic performance between CHADS2 and CHA2DS2-VASc in predicting stroke, or systemic embolism, in AF. We then assessed the quality of the included studies and pooled the C-statistics and 95% confidence intervals (95% CI). RESULTS: Eight studies were included. It was unsuitable to perform a direct meta-analysis because of high heterogeneity. When analyzed as a continuous variable, the C-statistic ranged from 0.60 to 0.80 (median 0.683) for CHADS2 and 0.64-0.79 (median 0.673) for CHA2DS2-VASc. When analyzed as a continuous variable in anticoagulation patients, the subgroup analysis showed that the pooled C-statistic (95% CI) was 0.660 (0.655-0.665) for CHADS2 and 0.667 (0.651-0.683) for CHA2DS2-VASc (no significant difference). For non-anticoagulation patients, the pooled C-statistic (95% CI) was 0.685 (0.666-0.705) for CHADS2 and 0.675 (0.656-0.694) for CHA2DS2-VASc (no significant difference). The average ratio of endpoint events in the low-risk group of CHA2DS2-VASc was less than CHADS2 (0.41% vs. 0.94%, P < 0.05). The average proportion of the moderate-risk group of CHA2DS2-VASc was lower than CHADS2 (11.12% vs. 30.75%, P < 0.05). CONCLUSIONS: The C-statistic suggests a similar clinical utility of the CHADS2 and CHA2DS2-VASc scores in predicting stroke and thromboembolism, but CHA2DS2- VASc has the important advantage of identifying extremely low-risk patients with atrial fibrillation, as well as classifying a lower proportion of patients as moderate risk.

[Distribution characteristics and risk evaluation of organochlorine pesticides in soil from relocation areas of the Danjiangkou Reservoir].

Twenty-six surface soil samples collected in Danjiangkou Reservoir were analyzed for organochlorine pesticides (OCPs) residues by GC-MS. The distribution characteristics, compositions and origin of OCPs were discussed. Pollution level and potential ecological risks of OCPs were also evaluated. The results showed that the concentration rang of total OCPs in soil was nd-249.37 ng x g(-1) (with a mean of 24.82 ng x g(-1)). The recent occurrence levels in soil were nd-69.68 ng x g(-1) for HCHs and nd-104.53 ng x g for DDTs. DDTs concentrations in soil were higher than those of HCHs. The OCPs residues in soil were mainly originated from the early residues, atmospheric deposition and recent input of OCPs components. The correlation between OCPs contents and organic matter contents in soil was not significant, indicating that the contents of OCPs in soil were also affected by other factors. Compared with other soil samples from different regions, the contents of OCPs in soil of relocation areas of the Danjiangkou Reservoir were at medium-low level. The study suggested that the OCPs in soil of relocation areas of the Danjiangkou Reservoir are in a state of low danger, whereas OCPs still display risks locally in some places.

Imposex effects on the veined rapa whelk (Rapana venosa) in Bohai Bay, China.

Environmentally relevant concentrations of organotin compounds (OTs) may trigger sex changes in marine invertebrates and pose a threat to the marine ecosystem. In this study, we investigated organotin levels and the biological responses of wild veined rapa whelk (Rapana venosa) from Lüjuhe district (LJH), Dashentang district (DST), and Nanpaihe district (NPH) in Bohai Bay, China. We found that 11.11 and 22.95 % of the veined rapa whelks from DST and NPH exhibited imposex characteristics with a relative penis size index (RPSI) of 12.50 and 12.31, respectively. The RNA/DNA ratio was significantly lower in females from DST than those from LJH (p < 0.05), and a slight increase in DNA damage was observed in females and imposex individuals compared to males. Moreover, less genetic distance occurred between LJH and NPH (0.016) than between LJH and DST (0.028), although they belonged to the same regional population. OTs analysis showed that triphenyltin chloride concentrations (41.45 ng/g dried weight) were significantly higher than tributyltin concentrations (9.51 ng/g dried weight) in tissues (p < 0.05), but no significant differences were observed in sediments (p > 0.05). In conclusion, the occurrence of imposex individuals and biological responses of the wild veined rapa whelk from Bohai Bay suggest that the marine ecosystem might be at risk.

[Characteristics of heavy metal pollution in Daninghe River and Modaoxi River of Three Gorges Reservoir areas].

In order to explore the potential ecological risk of heavy metals in Three Gorges Reservoir areas, the present study analyzed the heavy metals in sediments and wild crucain carp from Daning River and Modaoxi River which are two typical tributaries, and then the potential risk was evaluated using potential ecological risk index for sediments and comprehensive pollution index for fish, respectively. The results showed that concentrations of Zn and Cr were higher (Daning River: 78.31 and 83.98 mg x kg(-1); Modaoxi River: 99.03 and 94.20 mg x kg(-1)), while Cd was the lowest (Daning River: 0.62 mg x kg(-1); Modaoxi River: 0.75 mg x kg(-1)). Moreover, an obvious increasing trend of these elements was observed in these tributaries from upstream to downstream. For the wild crucain carp, the lowest concentrations of these elements were detected in muscles, and the highest concentrations were in the intestinal. However, no obvious increasing trend of these elements was observed from upstream to downstream. The potential ecological risk in sediments showed a high risk, while no risk was observed in fish.

Syntheses and cell-based phenotypic screen of novel 7-amino pyrido[2,3-d]pyrimidine-6-carbonitrile derivatives as potential antiproliferative agents.

A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC(50) value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC(50) value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.

Impact of 10 mg rosuvastatin daily or alternate-day on lipid profile and inflammatory markers.

BACKGROUND: Statins are commonly administrated daily, while rosuvastatin can be given every other day due to its longer half-lives. We evaluated the potential efficacy of alternate-day dosing of 10mg rosuvastatin compared with daily dosing of 10mg rosuvastatin with regarding to lipid and inflammatory markers in patients with dyslipidemia. METHODS: Thirty-seven patients were randomly divided into the 2 groups: alternate-day group (rosuvastatin 10mg every other day, n=19) and once-daily group (rosuvastatin 10mg every day, n=18) for 6 weeks. The primary endpoints of the study were changes of the serum concentrations of low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and interleukin-6 (IL-6) following 6-week rosuvastatin therapy. RESULTS: Baseline characteristics of the 2 groups were well balanced. LDL-C decreased by 37.5% after the once-daily dosing period and by 36.9% after alternate-day dosing period (p>0.05). Both dosing regimens provided similar improvement in high-density lipoprotein cholesterol and triglyceride. And also, both dosing regimens significantly decreased serum concentrations of CRP, which had an 18.3% reduction in once-daily dosing and a 16.7% reduction in alternate-day dosing of rosuvastatin (p>0.05). Moreover, the pattern of plasma IL-6 concentrations was also similar between the two groups (p>0.05). CONCLUSIONS: Alternate-day dosing of rosuvastatin could be effective comparable with once-daily dosing of rosuvastatin in Chinese patients in improving not only lipid profile but also inflammatory markers, which may provide some cost savings and increase the compliance of patients.

Construction and characterization of a normalized cDNA library from the river snail Bellamya aeruginosa after exposure to copper.

The construction of a normalized cDNA library is a popular tool for identifying novel biomarkers for monitoring environmental pollution. In the present study, a normalized cDNA library was constructed from the river snail Bellamya aeruginosa after exposure to Cu(2+) by using the SMART technique. The titer of the cDNA library was 1.78 × 10(6) pfu/ml, with a recombinant efficiency of 95.8%. In addition, from 6,000 randomly selected and sequenced clones, 5,473 high-quality ESTs were identified. After processing the sequences, 3,961 unigenes representing 897 contigs and 3,064 singlets were obtained with 27.6% redundancy. Analysis of expressed sequenced tags using COG and GO annotation and KEGG pathway data showed that a large group of genes related to growth and development, signal transduction, and defense mechanisms were present in the cDNA library. Based on our findings, this normalized cDNA library will provide a valuable resource for further research on functional genes and ecotoxicology in B. aeruginosa.