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排序方式: 共有236条查询结果,搜索用时 15 毫秒
151.
Xinyi Leng Fabien Scalzo Hing Lung Ip Mark Johnson Albert K. Fong Florence S. Y. Fan Xiangyan Chen Yannie O. Y. Soo Zhongrong Miao Liping Liu Edward Feldmann Thomas W. H. Leung David S. Liebeskind Ka Sing Wong 《PloS one》2014,9(5)
Background
Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.Methods
Patients with a symptomatic ICAS lesion of 70–99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.Results
Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (−2.46–0.79), 4.5 (2.2–20.6), and 7.4 (5.2–12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004–1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002–1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594–0.903; P = 0.014) and 0.776 (95% CI, 0.594–0.903; P = 0.002) in receiver operating characteristic analysis.Conclusions
Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70–99% luminal stenosis. 相似文献152.
Yangbo Sun Chaoqiang Jiang Kar Keung Cheng Weisen Zhang Gabriel M. Leung Tai Hing Lam C. Mary Schooling 《PloS one》2014,9(1)
Background
Dairy products consumption is increasingly common globally. Most of the evidence concerning dairy products comes from observational studies in western populations which are inevitably open to confounding. To triangulate the evidence concerning dairy products, we examined the associations of whole cow''s milk consumption with cardiovascular risk factors in a non-Western setting with a different pattern of milk consumption and cardiovascular diseases from Western populations.Methods
We used multivariable censored linear or logistic regression to examine cross-sectionally the adjusted associations of whole cow''s milk consumption (none (n = 14892), 1–3/week (n = 2689) and 3+/week (n = 2754)) with cardiovascular risk factors in Chinese (≥50 years) in the Guangzhou Biobank Cohort Study.Results
Whole cow''s milk consumption was negatively associated with systolic blood pressure (3+/week compared to none −2.56 mmHg, 95% confidence interval (CI) −3.63 to −1.49), diastolic blood pressure (−1.32 mmHg, 95% CI −1.87 to −0.77) and triglycerides (−0.06 mmol/L, 95% CI −0.11 to −0.002), but was positively associated with HDL-cholesterol (0.02 mmol/L,95% CI 0.01 to 0.04) and fasting glucose (0.08 mmol/L, 95% CI 0.01 to 0.16) adjusted for age, sex, phase of study, socio-economic position, lifestyle (smoking, alcohol use and physical activity) and adiposity, but had no obvious association with LDL-cholesterol or the presence of diabetes.Conclusions
Whole cow''s milk consumption had heterogeneous associations with cardiovascular risk factors. Higher whole cow''s milk consumption was associated with lower levels of specific cardiovascular risk factors which might suggest risk factor specific biological pathways with different relations to blood pressure and lipids than glucose. 相似文献153.
Jacqueline Chor Wing Tam Chun Hay Ko Chi Man Koon Zhang Cheng Wong Hing Lok Ching Po Lau Ping Chung Leung Kwok Pui Fung Wai Yee Chan Clara Bik San Lau 《PloS one》2015,10(10)
Angiogenesis is vitally important in diabetic wound healing. We had previously demonstrated that a Chinese 2-herb formula (NF3) significantly stimulated angiogenesis of HUVEC in wound healing. However, the molecular mechanism has not yet been elucidated. In line with this, global expression profiling of NF3-treated HUVEC was performed so as to assess the regulatory role of NF3 involved in the underlying signaling pathways in wound healing angiogenesis. The microarray results illustrated that different panels of differentially expressed genes were strictly governed in NF3-treated HUVEC in a time-regulated manner. The microarray analysis followed by qRT-PCR and western blotting verification of NF3-treated HUVEC at 6 h revealed the involvement of various genes in diverse biological process, e.g., MAP3K14 in anti-inflammation; SLC5A8 in anti-tumorogenesis; DNAJB7 in protein translation; BIRC5, EPCAM, INSL4, MMP8 and NPR3 in cell proliferation; CXCR7, EPCAM, HAND1 and MMP8 in migration; CXCR7, EPCAM and MMP8 in tubular formation; and BIRC5, CXCR7, EPCAM, HAND1, MMP8 and UBD in angiogenesis. After 16 h incubation of NF3, other sets of genes were shown with differential expression in HUVEC, e.g., IL1RAPL2 and NR1H4 in anti-inflammation; miR28 in anti-tumorogenesis; GRIN1 and LCN1 in anti-oxidation; EPB41 in intracellular signal transduction; PRL and TFAP2A in cell proliferation; miR28, PRL and SCG2 in cell migration; PRL in tubular formation; and miR28, NR1H4 and PRL in angiogenesis. This study provided concrete scientific evidence in support of the regulatory role of NF3 on endothelial cells involved in wound healing angiogenesis. 相似文献
154.
Lin Xu Chao Qiang Jiang Kar Keung Cheng Shiu Lun Ryan Au Yeung Wei Sen Zhang Tai Hing Lam Catherine Mary Schooling 《PloS one》2015,10(9)
Background
Observational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people.Methods
An instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak.Results
In men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis.Conclusion
In Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations. 相似文献155.
Xiaocong M. Ye Andrei W. Konradi Minghua Sun Shendong Yuan Danielle L. Aubele Michael Dappen Darren Dressen Albert W. Garofalo Jacek J. Jagodzinski Lee Latimer Gary D. Probst Hing L. Sham David Wone Ying-zi Xu Daniel Ness Elizabeth Brigham Grace T. Kwong Chris Willtis Guriqbal S. Basi 《Bioorganic & medicinal chemistry letters》2013,23(4):996-1000
Structure–activity relationship (SAR) of a novel, potent and metabolically stable series of benzo [3.2.1] bicyclic sulfonamide-pyrazoles as γ-secretase inhibitors are described. Compounds that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via oral dose, as well as those with high selectivity over Notch, are highlighted. 相似文献
156.
Dalal Alkazemi Grace M. Egeland L. Jackson Roberts II Hing M. Chan Stan Kubow 《Journal of lipid research》2013,54(7):1972-1979
Despite animal and in vitro studies demonstrating pro-oxidative effects of Hg, previous human work showed no relationship between tissue Hg and plasma levels of F2-isoprostanes (IsoPs), a whole-body oxidative stress marker. We hypothesized that another IsoP species, isofurans (IsoFs), was a more sensitive indicator of Hg-mediated oxidative stress, which can be modified by tissue Se status. A cross-sectional study was carried out involving individuals from a random subset (n = 233) of Inuit adults from a population-based survey (n = 2,595) of 36 Canadian Arctic Inuit communities to assess the relationships of plasma IsoPs to Se and Hg status indicators. F2-IsoPs were inversely correlated with blood Se (r = −0.186, P = 0.005) and toenail Se (r = −0.146, P = 0.044), but not correlated with Hg. IsoFs were inversely correlated with blood Se (r = −0.164, P = 0.014) and positively correlated with Hg (r = 0.228, P < 0.001) and Hg:Se (r = 0.340, P < 0.001). The strength of the correlations remained unchanged after multivariate adjustments. Multivariate analysis showed that F2-IsoPs were not positively associated with Hg but with Hg:Se (β = 0.148, P = 0.021). We conclude that Se and Hg status and their interactions are important factors modulating F2-IsoP and IsoF levels such that the Inuit may be protected from Hg-induced oxidative stress because of their high Se status. 相似文献
157.
Ang LH Chen W Yao Y Ozawa R Tao E Yonekura J Uemura T Keshishian H Hing H 《Developmental biology》2006,293(1):178-190
Lim Kinase (Limk) belongs to a phylogenetically conserved family of serine/threonine kinases, which have been shown to be potent regulators of the actin cytoskeleton. Despite accumulating evidence of its biochemical actions, its in vivo function has remained poorly understood. The association of the Limk1 gene with Williams Syndrome indicates that proteins of this family play a role in the nervous system. To unravel the cellular and molecular functions of Limk, we have either knocked out or activated the Limk gene in Drosophila. At the neuromuscular junction, loss of Limk leads to enlarged terminals, while increasing the activity of Limk leads to stunted terminals with fewer synaptic boutons. In the antennal lobe, loss of Limk abolishes the ability of p21-activated kinase (Pak) to alter glomerular development. In contrast, increase in Limk function leads to ectopic glomeruli, a phenotype suppressible by the coexpression of a hyperactive Cofilin gene. These results establish Limk as a critical regulator of Cofilin function and synapse development, and a downstream effector of Pak in vivo. 相似文献
158.
Yeh VS Kurukulasuriya R Madar D Patel JR Fung S Monzon K Chiou W Wang J Jacobson P Sham HL Link JT 《Bioorganic & medicinal chemistry letters》2006,16(20):5408-5413
A series of structurally novel and metabolically stable bridged bicyclic carbocycle and heterocycle adamantane replacements have been synthesized and biologically evaluated. Several of these compounds exhibit excellent human and mouse 11beta-HSD1 potency and 11beta-HSD2 selectivity. 相似文献
159.
Li G Hasvold LA Tao ZF Wang GT Gwaltney SL Patel J Kovar P Credo RB Chen Z Zhang H Park C Sham HL Sowin T Rosenberg SH Lin NH 《Bioorganic & medicinal chemistry letters》2006,16(8):2293-2298
Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea in the checkpoint kinase 1 (Chk1) enzyme, we modified R4, and to a lesser extent, R2, and R5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 microM) and enhanced doxorubicin cytotoxicity (IC50=0.44 microM) while displaying no single agent activity. 相似文献
160.
Peter E Morris Jay S Steingrub Bee Y Huang Shamay Tang Patrick M Liu Peter R Rhode Hing C Wong 《BMC pulmonary medicine》2012,12(1):1-8