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61.
Yongzhi Li Xiuhua Liu Dong Chen Zhichao Wei Bo Liu 《Journal of molecular modeling》2013,19(9):3619-3626
A tree-step computational approach has been applied to determine the lowest-energy conformers of luteolin-4′-O-β-D-glucoside (L4′G). Fifty-seven starting structures of the L4′G have been built, and then by performing with density functional theory (DFT) optimizations and second-order Møller-Plesset (MP2) calculations, the preferred conformations of L4′G are predicted. In order to test the accuracy of the computational approach, a hybrid Monte-Carlo multiple minimum (MCMM)/quantum mechanical (QM) approach is applied to determine the favorable conformers of L4′G. The alternative classification is employed to put similar conformations into the same catalogue according to the dihedral angles among the luteolin rings, glycosidic dihedral angles, and the orientations of hydroxyl and hydroxymethyl groups. The low-energy conformations are located after the optimizations at the HF/6-31G(d) and B3LYP/6-311+G(d) levels. Compared with the hybrid MCMM/QM approach, the tree-step computational approach not only remains accurate but also saves a lot of computing resources. Figure
Preferred conformations of luteolin-4′-O-β-D-glucoside in gas phase 相似文献
62.
Qiong Wu Chunhong Yang Yong Pan Fang Xiang Zhichao Liu Weihua Zhu Heming Xiao 《Journal of molecular modeling》2013,19(12):5159-5170
Periodic first-principles calculations have been performed to study the effect of high pressure on the geometric, electronic, and absorption properties of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) under hydrostatic pressures of 0–50 GPa. Obvious irregular changes in lattice constants, unit-cell angles, bond lengths, bond angles, and band gaps showed that crystalline LLM-105 undergoes four structural transformations at 8, 17, 25, and 42 GPa, respectively. The intramolecular H-bonds were strong at pressures of 0–41 GPa but weakened in the range 42–50 GPa. The lengths of the intermolecular H-bonds (<1.47 Å) indicated that these H-bonds have covalent character and tend to induce the formation of a new twelve-membered ring. Analysis of the DOS showed that the interactions between electrons, especially the valence electrons, strengthen under the influence of pressure. The p states play a very important role in chemical reactions of LLM-105. The absorption spectrum of LLM-105 displayed more bands—as well as stronger bands—in the fundamental absorption region when the pressure was high rather than low. A new absorption peak due to O–H stretching appeared at 18.3 eV above 40 GPa, indicating that covalent O–H bonds and a new twelve-membered ring are present in LLM-105. 相似文献
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Jia-Xin Jiang Karen J. Aitken Chris Sotiropolous Tyler Kirwan Trupti Panchal Nicole Zhang Shuye Pu Shoshana Wodak Cornelia Tolg Darius J. B?gli 《PloS one》2013,8(8)
Extracellular matrix changes are often crucial inciting events for fibroproliferative disease. Epigenetic changes, specifically DNA methylation, are critical factors underlying differentiated phenotypes. We examined the dependency of matrix-induced fibroproliferation and SMC phenotype on DNA methyltransferases. The cooperativity of matrix with growth factors, cell density and hypoxia was also examined. Primary rat visceral SMC of early passage (0–2) were plated on native collagen or damaged/heat-denatured collagen. Hypoxia was induced with 3% O2 (balanced 5% CO2 and 95% N2) over 48 hours. Inhibitors were applied 2–3 hours after cells were plated on matrix, or immediately before hypoxia. Cells were fixed and stained for DNMT3A and smooth muscle actin (SMA) or smooth muscle myosin heavy chain. Illumina 450 K array of CpG sites was performed on bisulfite-converted DNA from smooth muscle cells on damaged matrix vs native collagen. Matrix exquisitely regulates DNMT3A localization and expression, and influences differentiation in SMCs exposed to denatured matrix +/− hypoxia. Analysis of DNA methylation signatures showed that Matrix caused significant DNA methylation alterations in a discrete number of CpG sites proximal to genes related to SMC differentiation. Matrix has a profound effect on the regulation of SMC phenotype, which is associated with altered expression, localization of DNMTs and discrete changes DNA methylation. 相似文献
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Ran Liu Miao Yang Yanli Meng Juan Liao Jingyi Sheng Yuepu Pu Lihong Yin Sun Jung Kim 《PloS one》2013,8(10)
Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC. 相似文献
68.
Kuo-How Huang Kuan-Lin Kuo I-Lin Ho Hong-Chiang Chang Yuan-Ting Chuang Wei-Chou Lin Ping-Yi Lee Shih-Chen Chang Chih-Kang Chiang Yeong-Shiau Pu Chien-Tso Chou Chen-Hsun Hsu Shing-Hwa Liu 《PloS one》2013,8(12)
Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER) stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA), bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC. 相似文献
69.
Objectives
We investigated the effect of a nationwide educational program following surviving sepsis campaign (SSC) guidelines. Physicians’ clinical practice in sepsis care and patient mortality rate for severe sepsis were analyzed using a nationally representative cohort.Methods
Hospitalizations for severe sepsis with organ failure from 1997 to 2008 were extracted from Taiwan’s National Health Insurance Research Database (NHIRD), and trends in sepsis incidence and mortality rates were analyzed. A before-and-after study design was used to evaluate changes in the utilization rates of SSC items and changes in severe sepsis mortality rates occurred after a national education program conducted by the Joint Taiwan Critical Care Medicine Committee since 2004. A total of 39,706 hospitalizations were analyzed, which consisted of a pre-intervention cohort of 14,848 individuals (2000-2003) and a post-intervention cohort of 24,858 individuals (2005-2008).Results
The incidence rate of severe sepsis increased from 1.88 per 1,000 individuals in 1997 to 5.07 per 1,000 individuals in 2008. The cumulative mortality rate decreased slightly from 48.2% for the pre-intervention cohort to 45.9% for the post-intervention cohort. The utilization rates of almost all SSC items changed significantly between the pre-intervention and post-intervention cohorts. These changes of utilization rates were found to be associated with mild reduction in mortality rate.Conclusion
The nationwide education program through a national professional society has a significant impact on physicians’ clinical practice and resulted in a slight but significant reduction of severe sepsis mortality rate. 相似文献70.