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991.
992.
Gan Q Thiébaud P Thézé N Jin L Xu G Grant P Owens GK 《The Journal of biological chemistry》2011,286(24):21853-21864
WD repeat-containing protein 5 (WDR5) is a common component of mammalian mixed lineage leukemia methyltransferase family members and is important for histone H3 lysine 4 methylation (H3K4me), which has been implicated in control of activation of cell lineage genes during embryogenesis. However, WDR5 has not been considered to play a specific regulatory role in epigenetic programming of cell lineage because it is ubiquitously expressed. Previous work from our laboratory showed the appearance of histone H3K4me within smooth muscle cell (SMC)-marker gene promoters during the early stages of development of SMC from multipotential embryonic cells but did not elucidate the underlying mechanisms that mediate SMC-specific and locus-selective H3K4me. Results presented herein show that knockdown of WDR5 significantly decreased SMC-marker gene expression in cultured SMC differentiation systems and in Xenopus laevis embryos in vivo. In addition, we showed that WDR5 complexes within SMC progenitor cells contained H3K4 methyltransferase enzymatic activity and that knockdown of WDR5 selectively decreased H3K4me1 and H3K4me3 enrichment within SMC-marker gene promoter loci. Moreover, we present evidence that it is recruited to these gene promoter loci through interaction with a SMC-selective pituitary homeobox 2 (Pitx2). Taken together, studies provide evidence for a novel mechanism for epigenetic control of SMC-marker gene expression during development through interaction of WDR5, homeodomain proteins, and chromatin remodeling enzymes. 相似文献
993.
Romero-Guido C Belo I Ta TM Cao-Hoang L Alchihab M Gomes N Thonart P Teixeira JA Destain J Waché Y 《Applied microbiology and biotechnology》2011,89(3):535-547
The consumers’ demand for natural flavour and fragrances rises. To be natural, compounds have to result from the extraction
of natural materials and/or to be transformed by natural means such as the use of enzymes or whole cells. Fungi are able to
transform some fatty acids into lactones that can thus be natural. Although some parts of this subject have been reviewed
several times, the present article proposes to review the different pathways utilised, the metabolic engineering strategies
and some current concerns on the reactor application of the transformation including scaling up data. The main enzymatic steps
are hydroxylation and β-oxidation in the traditional way, and lactone desaturation or Baeyer–Villiger oxidation. Although
the pathway to produce γ-decalactone is rather well known, metabolic engineering strategies may result in significant improvements
in the productivity. For the production of other lactones, a key step is the hydroxylation of fatty acids. Beside the biotransformation,
increasing the production of the various lactones requires from biotechnologists to solve two main problems which are the
toxicity of lactones toward the producing cell and the aeration of the emulsified reactor as the biochemical pathway is very
sensitive to the level of available oxygen. The strategies employed to resolve these problems will be presented. 相似文献
994.
Tran Thanh Vu Thi Quynh Chi Mohd Puad Abdullah Hishamuddin Omar Mostafa Noroozi Huynh Ky Suhaimi Napis 《Molecular biology reports》2011,38(1):177-182
Green microalga Ankistrodesmus convolutus Corda is a fast growing alga which produces appreciable amount of carotenoids and polyunsaturated fatty acids. To our knowledge,
this is the first report on the construction of cDNA library and preliminary analysis of ESTs for this species. The titers
of the primary and amplified cDNA libraries were 1.1 × 106 and 6.0 × 109 pfu/ml respectively. The percentage of recombinants was 97% in the primary library and a total of 337 out of 415 original
cDNA clones selected randomly contained inserts ranging from 600 to 1,500 bps. A total of 201 individual ESTs with sizes ranging
from 390 to 1,038 bps were then analyzed and the BLASTX score revealed that 35.8% of the sequences were classified as strong
match, 38.3% as nominal and 25.9% as weak match. Among the ESTs with known putative function, 21.4% of them were found to
be related to gene expression, 14.4% ESTs to photosynthesis, 10.9% ESTs to metabolism, 5.5% ESTs to miscellaneous, 2.0% to
stress response, and the remaining 45.8% were classified as novel genes. Analysis of ESTs described in this paper can be an
effective approach to isolate and characterize new genes from A. convolutus and thus the sequences obtained represented a significant contribution to the extensive database of sequences from green
microalgae. 相似文献
995.
Clément Pimouguet Mélanie Le Goff Rodolphe Thiébaut Jean Fran?ois Dartigues Catherine Helmer 《CMAJ》2011,183(2):E115-E127
Background
We conducted a meta-analysis of randomized controlled trials to assess the effectiveness of disease-management programs for improving glycemic control in adults with diabetes mellitus and to study which components of programs are associated with their effectiveness.Methods
We searched several databases for studies published up to December 2009. We included randomized controlled trials involving adults with type 1 or 2 diabetes that evaluated the effect of disease-management programs on glycated hemoglobin (hemoglobin A1C) concentrations. We performed a meta-regression analysis to determine the effective components of the programs.Results
We included 41 randomized controlled trials in our review. Across these trials, disease-management programs resulted in a significant reduction in hemoglobin A1C levels (pooled standardized mean difference between intervention and control groups −0.38 [95% confidence interval −0.47 to −0.29], which corresponds to an absolute mean difference of 0.51%). The finding was robust in the sensitivity analyses based on quality assessment. Programs in which the disease manager was able to start or modify treatment with or without prior approval from the primary care physician resulted in a greater improvement in hemoglobin A1C levels (standardized mean difference −0.60 v. −0.28 in trials with no approval to do so; p < 0.001). Programs with a moderate or high frequency of contact reported a significant reduction in hemoglobin A1C levels compared with usual care; nevertheless, only programs with a high frequency of contact led to a significantly greater reduction compared with low-frequency contact programs (standardized mean difference −0.56 v. −0.30, p = 0.03).Interpretation
Disease-management programs had a clinically moderate but significant impact on hemoglobin A1C levels among adults with diabetes. Effective components of programs were a high frequency of patient contact and the ability for disease managers to adjust treatment with or without prior physician approval.Despite well-established recommendations for diabetes care,1–3 quality of care still needs to be improved. Although many nonpharmacologic strategies (patient education, psychological intervention, dietary education, self-monitoring and telemedicine) have been developed, their effectiveness is still unclear.4–6 “Disease management” is a structured, multi-faceted intervention that includes several of the above-mentioned components. In two recent meta-analyses, disease management was associated with an improvement in glycemic control, as assessed by a mean reduction in hemoglobin A1C concentration of 0.52% and 0.81%.7,8 Disease management seems to be more effective than single strategies such as clinician education, patient education or promotion of self-management.7Because disease-management programs are heterogeneous, the effective components need to be identified to improve program implementation. Previous studies have evaluated the efficacy of some program components.7,8 Independent medication changes by the disease manager appear to be particularly effective.7 However, other important factors such as the intensity of the intervention have not been previously evaluated.We conducted a meta-analysis of randomized controlled trials (RCTs) involving adults with type 1 or 2 diabetes mellitus that evaluated the effect of disease-management programs on hemoglobin A1C levels. We determined the effective components of the programs, considering both the type of component and the intensity of the intervention. 相似文献996.
Van HT Khadka DB Yang SH Le TN Cho SH Zhao C Lee IS Kwon Y Lee KT Kim YC Cho WJ 《Bioorganic & medicinal chemistry》2011,19(18):5311-5320
Benzo[3,4]azepino[1,2-b]isoquinolinones were designed and developed as constraint forms of 3-arylisquinolines with an aim to inhibit topoisomerase I (topo I). Ring closing metathesis (RCM) of 3-arylisoquinolines with suitable diene moiety provided seven membered azepine rings of benzoazepinoisoquinolinones. Spectral analyses of these heterocyclic compounds demonstrated that the methylene protons of the azepine rings are nonequivalent. The shielding environment experienced by these geminal hydrogens differs unusually by 2.21ppm. As expected, benzoazepinoisoquinolinones displayed potent cytotoxicity. However, cytotoxic effects of the compounds were not related to topo I inhibition which is explained by non-planar conformation of the rigid compounds incapable of intercalating between DNA base pairs. In contrast, flexible 3-arylisoquinoline 8d attains active conformation at drug target site to exhibit topo I inhibition identical to cytotoxic alkaloid, camptothecin (CPT). 相似文献
997.
Nhiem NX Lim HY Kiem PV Minh CV Thu VK Tai BH Quang TH Song SB Kim YH 《Bioorganic & medicinal chemistry letters》2011,21(20):6143-6147
Two new oleanane-type triterpene saponins, tarasaponin IV (1) and elatoside L (2), and four known; stipuleanoside R(2) (3), kalopanax-saponin F (4), kalopanax-saponin F methylester (5), and elatoside D (6) were isolated from the bark of Aralia elata. Kalopanax-saponin F methyl ester was isolated from nature for the first time. Their chemical structures were elucidated using the chemical and physical methods as well as good agreement with those of reported in the literature. Oleanane-type triterpene saponins are the main component of A. elata. All compounds were investigated the anti-inflammatory activity. We measured their inhibition of NF-κB and activation of PPARs activities in HepG2 cells using luciferase reporter system. As results, compounds 2 and 4 were found to inhibit NF-κB activation stimulated by TNFα in a dose-dependent manner with IC(50) values of 4.1 and 9.5 μM, respectively, when compared with that of positive control, sulfasalazine (0.9 μM). Compounds 2 and 4 also inhibited TNFα-induced expression of iNOS and COX-2 mRNA. Furthermore, compounds 1-6 were evaluated PPAR activity using PPAR subtype transactivation assays. Among of them, compounds 4-6 significantly increased PPARγ transactivation. However, compounds 4-6 did not activate in any other PPAR subtypes. 相似文献
998.
Chau VM Phan VK Nguyen X Nguyen XC Nguyen PT Nguyen HN Hoang le TA Do CT Thuy DT Kang HK Jang HD Kim YH 《Bioorganic & medicinal chemistry letters》2011,21(7):2155-2159
Two new diterpenes, lobocompactols A (1) and B (2), and five known compounds (3-7) were isolated from the methanol extract of the soft coral Lobophytum compactum using combined chromatographic methods and identified based on NMR and MS data. Each compound was evaluated for cytotoxic activity against A549 (lung) and HL-60 (acute promyelocytic leukemia) human cancer cell lines. Among them, compound 5 exhibited strong cytotoxic activity against the A549 cell line with an IC50 of 4.97 ± 0.06 μM. Compounds 3, 4, and 7 showed moderate activity with IC50 values of 23.03 ± 0.76, 31.13 ± 0.08, and 36.45 ± 0.01 μM, respectively. The cytotoxicity of 5 on the A549 cells was comparable to that of the positive control, mitoxantrone (MX). All compounds exhibited moderate cytotoxicity against the HL-60 cell line, with IC50 values ranging from 17.80 ± 1.43 to 59.06 ± 2.31 μM. Their antioxidant activity was also measured using oxygen radical absorbance capacity method, compounds 1 and 2 exhibiting moderate peroxyl radical scavenging activity of 1.4 and 1.3 μM Trolox equivalents, respectively, at a concentration of 5 μM. 相似文献
999.
Nguyen TT Ryu HJ Lee SH Hwang S Breton V Rhee JH Kim D 《Bioorganic & medicinal chemistry letters》2011,21(10):3088-3091
The 3C-like protease (3CLpro) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308 307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from −14.0 to −17.09 kcal mol−1 were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CLpro. Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CLpro expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC50 ranged from 38.57 ± 2.41 to 101.38 ± 3.27 μM. Two strong 3CLpro inhibitors were further identified as competitive inhibitors of 3CLpro with Ki values of 9.11 ± 1.6 and 9.93 ± 0.44 μM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CLpro were also identified. 相似文献
1000.