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Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.
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Ratas , Ratones , Animales , Rosuvastatina Cálcica/uso terapéutico , Factor C de Crecimiento Endotelial Vascular , Células Endoteliales/metabolismo , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica , HDL-Colesterol , Sistema Linfático/metabolismoRESUMEN
OBJECTIVE@#To evaluate the role of miR-106b-5p in the regulation of gene expression in endothelial cells.@*METHODS@#The Taqman low-density microRNAs (miRNAs) array (TLDA) was used to identify miRNA expression profiles in the plasma of patients with atherosclerotic coronary artery disease (CAD) (atherosclerosis group, n=9) and individuals without atherosclerotic CAD disease (control group, n=9). A weighed and undirected miRNA coexpression network analysis was performed to investigate the interactions among miRNAs in the two groups. MiR-106b-5p, whose coexpression pattern in atherosclerosis group was most different from that of control group, was further studied. Human umbilical vein endothelial cells (HUVEC) were transfected with miR-106b-5p mimic or negative control mimic, and Affymetrix GeneChip Human Transcriptome Array 2.0 was used to screen the differential gene expression profiles after transfection. And the signal transduction pathway of differential gene profiles was further analyzed in Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway database. After parsing the whole KEGG database, all differentially expressed genes involved pathways were extracted, and the hypergeometric distribution was used to calculate the pathway enrichment.@*RESULTS@#The coexpression pattern of the patients with atherosclerosis (140 nodes, 1 154 edges) differed from that of the non-atherosclerosis control group (140 nodes, 612 edges). The analysis of array data with significant analysis of microarray (SAM) identified 746 significantly deregulated genes (fold change ≥ 1.5 and false discovery rate < 0.01) altered by overexpression of miR-106b-5p with miR-106b-5p mimic in HUVEC. By calculating the pathway enrichment, we found that multiple signaling pathways enriched in differential gene profiles were closely related to the process of formation and rupture of atherosclerotic plaque, including phosphatidylinositol-3 kinase (PI3K)/ protein kinase B (PKB, also called Akt), mammalian target of rapamycin (mTOR), transforming growth factor-β (TGF-β), janus kinase / signal transducer and activator of transcription (Jak-STAT), tumor necrosis factor (TNF), toll like receptor (TLR) and hypoxia-inducible factor 1α (HIF-1α) and other signal pathways.@*CONCLUSION@#The coexpression pattern of miRNAs in plasma of patients with atherosclerosis is more significantly changed than that of individuals without atherosclerotic disease. MiR-106b-5p, which shows the most significant difference between groups, targets multiple signal pathways in vascular endothelial cells, and might play an important role in the regulatory network of atherosclerotic gene expression.
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Humanos , Células Endoteliales de la Vena Umbilical Humana , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-akt , Transducción de SeñalRESUMEN
Background@#Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells.@*Methods@#Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and arranged to harvest EMPs in two parts: the first part consisted of EMP and EMP and the second part included EMP, EMP, and EMP. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared.@*Results@#Compared with EMP- and EMP-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40, P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52, P < 0.01), the number of tube formations was markedly reduced by 70% in the EMP group (P < 0.001) in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMP was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed that TGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression of TGFβ2 in HUVECs was inhibited by treatment with EMP and EMP.@*Conclusions@#MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.
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Humanos , Hipoxia de la Célula , Genética , Fisiología , Movimiento Celular , Genética , Fisiología , Células Endoteliales , Metabolismo , Células Endoteliales de la Vena Umbilical Humana , Metabolismo , MicroARNs , Genética , Metabolismo , Neovascularización Fisiológica , Genética , Fisiología , Factor de Crecimiento Transformador beta2 , Genética , MetabolismoRESUMEN
Water samples were collected from Hun River to research the change in the concentration of dissolved copper and its distribution as well as accumulation during the dry season in 2013. The mean concentrations of dissolved copper in Hun River were 0.1057-0.1533 mg/l during the dry season. The results indicated that the most severe dissolved copper pollution were associated with the mining area, industrial area, and living area along the Hun River. The results also indicated that controlling the sources of copper pollution effectively reduced the concentration of dissolved copper in Hun River. The concentration function about time and spatial coordinate, average concentration function about time coordinate, average concentration function about spatial coordinate, and bounded mean oscillation space were used to evaluate the extent of copper pollution in Hun River. The error function, quartiles, and curve fitting tool were performed to determine the stations with high concentration of dissolved copper in Hun River. We furthermore obtained the upper and lower bounds of the error between two kinds of bounded mean oscillation spaces to explore the migration of copper pollution in Hun River. The results of the average concentration function and bounded mean oscillation space revealed that the long-term control measures of copper pollution and short-term control measures of copper pollution, the control of copper pollution in large watershed, and the control of copper pollution in small watershed in Hun River should be combined with each other. The strict policy and pollution control strategy should be implemented to ensure that the water of the Hun River meets the natural environment standard for the growth of aquatic life and human.
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Cobre/análisis , Monitoreo del Ambiente , Ríos/química , Contaminantes Químicos del Agua/análisis , China , Modelos TeóricosRESUMEN
In order to study the potential application value of lavender volatile oil (LVO), the chemical composition of the volatile oil of lavender was analyzed by GC-MS, and the mouse model of Alzheimer's disease (AD) was established. Additionally, the antioxidant enzymes activity of T-SOD, GSH-PX, CAT and MDA content were studied. Experimental results showed that 55 kinds of chemical constituents including terpene, terpene alcohol and ester compounds from LVO were identified, and the content of linalool and linalyl acetate was the highest, accounting for 49.71% of the total volatile oil. The ability of mouse platform memory was improved significantly. The levels of GSH-PX, CAT and T-SOD of mouse brain tissue in the treatment group were significantly higher than those in the model group (P<0.05). The level of MDA reached the maximum value in the model group, while there was no notable difference between the levels of MDA in the drug group and the normal group. The result indicated the significant oxidative activity of LVO, the possibility of induced oxidative stress reduction in neurons, and the reversal effect of memory acquired disorder.
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<p><b>BACKGROUND</b>Apoptosis of endothelial cells (ECs) plays a key role in the development of atherosclerosis and there are also evidence indicated that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a viable target in therapeutic approaches to prevent vascular ECs apoptosis. Aberrant miR-106b-5p expression has been reported in the plasma of patients with unstable atherosclerotic plaques. However, the role and underlying mechanism of miR-106-5p in the genesis of atherosclerosis have not been addressed. In this study, we explored the anti-apoptotic role of miR-106-5p by regulating PTEN expression in vascular ECs.</p><p><b>METHODS</b>Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the expression levels of miR-106b-5p in human atherosclerotic plaques and normal vascular tissues. Human umbilical vein endothelial cells (HUVEC) were transfected with miR-106b-5p mimic or negative control mimic, and apoptosis was induced by serum starvation and tumor necrosis factor-α (TNF-α) treat. Western blotting and real-time RT-PCR experiments were used to detect PTEN expression levels and TNF-α-induced apoptosis was evaluated by the activation of caspase-3 and cell DNA fragmentation levels in HUVEC.</p><p><b>RESULTS</b>The expression of miR-106b-5p was significantly downregulated in plaques than in normal vascular tissues. TNF-α significantly downregulated miR-106b-5p expression levels and upregulated activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Overexpression of miR-106b-5p with miR-106b-5p mimic inhibited PTEN expression and TNF-α-induced apoptosis in HUVEC. Luciferase reporter assays confirmed that miR-106b-5p binds to PTEN mRNA 3' untranslated region site.</p><p><b>CONCLUSION</b>MiR-106b-5p could inhibit the expression of PTEN in vascular ECs, which could block TNF-α-induced activation of caspase-3, thus prevent ECs apoptosis in atherosclerosis diseases.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis , Células Cultivadas , Células Endoteliales , Biología Celular , Metabolismo , Células Endoteliales de la Vena Umbilical Humana , Biología Celular , Metabolismo , MicroARNs , Genética , Metabolismo , Fosfohidrolasa PTEN , Metabolismo , Unión Proteica , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa , FarmacologíaRESUMEN
Neuroimaging studies of obsessive-compulsive disorder have found abnormalities in orbitofronto-striato-thalamic circuitry, including the orbitofrontal cortex, anterior cingulate cortex, caudate, and thalamus, but few studies have explored abnormal intrinsic or spontaneous brain activity in the resting state. We investigated both intra- and inter-regional synchronized activity in twenty patients with obsessive-compulsive disorder and 20 healthy controls using resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) and functional connectivity methods were used to analyze the intra- and inter-regional synchronized activity, respectively. Compared with healthy controls, patients with obsessive-compulsive disorder showed significantly increased ReHo in the orbitofrontal cortex, cerebellum, and insula, and decreased ReHo in the ventral anterior cingulate cortex, caudate, and inferior occipital cortex. Based on ReHo results, we determined functional connectivity differences between the orbitofrontal cortex and other brain regions in both patients with obsessive-compulsive disorder and controls. We found abnormal functional connectivity between the orbitofrontal cortex and ventral anterior cingulate cortex in patients with obsessive-compulsive disorder compared with healthy controls. Moreover, ReHo in the orbitofrontal cortex was correlated with the duration of obsessive-compulsive disorder. These findings suggest that increased intra- and inter-regional synchronized activity in the orbitofrontal cortex may have a key role in the pathology of obsessive-compulsive disorder. In addition to orbitofronto-striato-thalamic circuitry, brain regions such as the insula and cerebellum may also be involved in the pathophysiology of obsessive-compulsive disorder.
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Encéfalo/fisiopatología , Trastorno Obsesivo Compulsivo/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Pacientes Ambulatorios , DescansoRESUMEN
<p><b>OBJECTIVE</b>The aim of this study was to assess the safety of fenofibrate-statin combination therapy.</p><p><b>METHODS</b>Medline, Cochrane Library, Web of Knowledge and CNKI were searched for 2184 randomized controlled trials. Finally, twenty-six studies with a total of 9494 participants were included in this analysis.</p><p><b>RESULTS</b>Compared with statins group, the fenofibrate-statin group had significantly higher incidence of aminotransferase elevations (OR 1.67, 95%CI 1.22-2.30, P < 0.05) . The two groups had identical incidence of creatin kinase elevations (OR 0.86, 95%CI 0.62-1.20, P > 0.05) , muscle-associated adverse events (OR 0.98, 95%CI 0.88-1.09, P > 0.05) and withdrawals due to hepatotoxicity or muscle toxicity. The safety of fenofibrate + standard-dose statin regimens were similar to those in fenofibrate-statin group.</p><p><b>CONCLUSION</b>Combined fenofibrate-statin treatment is generally safe and well tolerated, liver function should be monitored before and during and after therapy.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Terapia Combinada , Fenofibrato , Usos Terapéuticos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Usos Terapéuticos , Hipolipemiantes , Usos Terapéuticos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
<p><b>BACKGROUND</b>Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years.</p><p><b>METHODS</b>The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010).</p><p><b>RESULTS</b>Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals.</p><p><b>CONCLUSIONS</b>The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors.</p>