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排序方式: 共有226条查询结果,搜索用时 15 毫秒
41.
Kumar JS Majo VJ Sullivan GM Prabhakaran J Simpson NR Van Heertum RL Mann JJ Parsey RV 《Bioorganic & medicinal chemistry》2006,14(12):4029-4034
Synthesis and evaluation of [O-methyl-11C](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [11C]SN003 ([11C]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [11C]SN003 is 30 min from EOB using [11C]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with >99% chemical and radiochemical purities and a specific activity of >2000 Ci/mmol. PET studies in baboon show that [11C]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain. 相似文献
42.
Joana M Xavier Ana L Morgado Cecília MP Rodrigues 《Cell cycle (Georgetown, Tex.)》2014,13(22):3576-3589
The low survival and differentiation rates of stem cells after either transplantation or neural injury have been a major concern of stem cell-based therapy. Thus, further understanding long-term survival and differentiation of stem cells may uncover new targets for discovery and development of novel therapeutic approaches. We have previously described the impact of mitochondrial apoptosis-related events in modulating neural stem cell (NSC) fate. In addition, the endogenous bile acid, tauroursodeoxycholic acid (TUDCA) was shown to be neuroprotective in several animal models of neurodegenerative disorders by acting as an anti-apoptotic and anti-oxidant molecule at the mitochondrial level. Here, we hypothesize that TUDCA might also play a role on NSC fate decision. We found that TUDCA prevents mitochondrial apoptotic events typical of early-stage mouse NSC differentiation, preserves mitochondrial integrity and function, while enhancing self-renewal potential and accelerating cell cycle exit of NSCs. Interestingly, TUDCA prevention of mitochondrial alterations interfered with NSC differentiation potential by favoring neuronal rather than astroglial conversion. Finally, inhibition of mitochondrial reactive oxygen species (mtROS) scavenger and adenosine triphosphate (ATP) synthase revealed that the effect of TUDCA is dependent on mtROS and ATP regulation levels. Collectively, these data underline the importance of mitochondrial stress control of NSC fate decision and support a new role for TUDCA in this process. 相似文献
43.
Mitochondrial dysfunction plays a critical role in the development of cardiac hypertrophy and heart failure. So mitochondria are emerging as one of the important druggable targets in the management of cardiac hypertrophy and other associated complications. In the present study, effects of ethanolic extract of Boerhaavia diffusa (BDE), a green leafy vegetable against mitochondrial dysfunction in angiotensin II (Ang II) induced hypertrophy in H9c2 cardiomyoblasts was evaluated. H9c2 cells challenged with Ang II exhibited pathological hypertrophic responses and mitochondrial dysfunction which was evident from increment in cell volume (49.09±1.13%), protein content (55.17±1.19%), LDH leakage (58.74±1.87%), increased intracellular ROS production (26.25±0.91%), mitochondrial superoxide generation (65.06±2.27%), alteration in mitochondrial transmembrane potential (ΔΨm), opening of mitochondrial permeability transition pore (mPTP) and mitochondrial swelling. In addition, activities of mitochondrial respiratory chain complexes (I-IV), aconitase, NADPH oxidase, thioredoxin reductase, oxygen consumption rate and calcium homeostasis were evaluated. Treatment with BDE significantly prevented the generation of intracellular ROS and mitochondrial superoxide radicals and protected the mitochondria by preventing dissipation of ΔΨm, opening of mPTP, mitochondrial swelling and enhanced the activities of respiratory chain complexes and oxygen consumption rate in H9c2 cells. Activities of aconitase and thioredoxin reductase which was lowered (33.77±0.68% & 45.81±0.71% respectively) due to hypertrophy, were increased in BDE treated cells (P≤0.05). Moreover, BDE also reduced the intracellular calcium overload in Ang II treated cells. Overall results revealed the protective effects of B. diffusa against mitochondrial dysfunction in hypertrophy in H9c2 cells and the present findings may shed new light on the therapeutic potential of B. diffusa in addition to its nutraceutical potentials. 相似文献
44.
Gagandeep Kaur Walia Vipin Gupta Aastha Aggarwal Mohammad Asghar Frank Dudbridge Nicholas Timpson Nongmaithem Suraj Singh M. Ravi Kumar Sanjay Kinra Dorairaj Prabhakaran K. Srinath Reddy Giriraj Ratan Chandak George Davey Smith Shah Ebrahim 《PloS one》2014,9(7)
Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations. 相似文献
45.
46.
Robert Gramling Kathi L Heffner William MP Klein Laura E Zajac Mary Roberts Charles B Eaton 《BioPsychoSocial medicine》2010,4(1):11
Background
More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction). 相似文献47.
Iris M Costa Tallybia HT Nasser Marilene Demasi Rafaella MP Nascimento Luis ES Netto Sayuri Miyamoto Fernanda M Prado Gisele Monteiro 《BMC microbiology》2011,11(1):268
Background
The gene YCL047C, which has been renamed promoter of filamentation gene (POF1), has recently been described as a cell component involved in yeast filamentous growth. The objective of this work is to understand the molecular and biological function of this gene.Results
Here, we report that the protein encoded by the POF1 gene, Pof1p, is an ATPase that may be part of the Saccharomyces cerevisiae protein quality control pathway. According to the results, Δpof1 cells showed increased sensitivity to hydrogen peroxide, tert-butyl hydroperoxide, heat shock and protein unfolding agents, such as dithiothreitol and tunicamycin. Besides, the overexpression of POF1 suppressed the sensitivity of Δpct1, a strain that lacks a gene that encodes a phosphocholine cytidylyltransferase, to heat shock. In vitro analysis showed, however, that the purified Pof1p enzyme had no cytidylyltransferase activity but does have ATPase activity, with catalytic efficiency comparable to other ATPases involved in endoplasmic reticulum-associated degradation of proteins (ERAD). Supporting these findings, co-immunoprecipitation experiments showed a physical interaction between Pof1p and Ubc7p (an ubiquitin conjugating enzyme) in vivo.Conclusions
Taken together, the results strongly suggest that the biological function of Pof1p is related to the regulation of protein degradation.48.
Sampling properties of DNA sequence data in phylogenetic analysis 总被引:20,自引:6,他引:20
We inferred phylogenetic trees from individual genes and random samples of
nucleotides from the mitochondrial genomes of 10 vertebrates and compared
the results to those obtained by analyzing the whole genomes. Individual
genes are poor samples in that they infrequently lead to the whole-genome
tree. A large number of nucleotide sites is needed to exactly determine the
whole-genome tree. A relatively small number of sites, however, often
results in a tree close to the whole-genome tree. We found that blocks of
contiguous sites were less likely to lead to the whole-genome tree than
samples composed of sites drawn individually from throughout the genome.
Samples of contiguous sites are not representative of the entire genome, a
condition that violates a basic assumption of the bootstrap method as it is
applied in phylogenetic studies.
相似文献
49.
50.
Prabhakaran Vasantha-Srinivasan Muthiah Chellappandian Sengottayan Senthil-Nathan Athirstam Ponsankar Annamalai Thanigaivel Sengodan Karthi Edward-Sam Edwin Selvaraj Selin-Rani Kandaswamy Kalaivani Filippo Maggi Giovanni Benelli 《Journal of Asia》2018,21(4):1466-1472
Fresh leaves of Piper betle Linn. (Piperales: Piperaceae) and Sphaeranthus indicus Linn. (Asterales: Asteraceae), commonly known as betel leaves and East Indian globe thistle, respectively, were harvested and steam distilled for the extraction of P. betle and S. indicus crude volatile oils (Pb-CVO and Si-CVO, respectively). LC50 calculated on 3rd instar larvae of dengue mosquito Aedes aegypti Linn. (Diptera: Culicidae) was 42.17?ppm for PbSi-CVO (i.e., herbal formulation based on the EOs of P. betle and S. indicus). The larval and pupal duration were significantly longer post-treatment with 100?ppm of PbSi-CVO, if compared to control. We observed that PbSi-CVO significantly altered the detoxifying enzymes GST and CYP450 compared to the expression of control. Sub-lethal concentrations of PbSi-CVO showed strong repellent properties against dengue mosquitoes, without adverse reactions on the volunteers experiencing the repellent assays. Lastly, the adulticidal activity of PbSi-CVO was studied. Overall, our study outlined that this herbal product represents a promising candidate for the development of botanical based adulticidal agents. 相似文献