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91.
Dhuru S Bhedi D Gophane D Hirbhagat K Nadar V More D Parikh S Dalal R Fonseca LC Kharas F Vadnal PY Vishwakarma RA Sivaramakrishnan H 《Bioorganic & medicinal chemistry letters》2011,21(12):3784-3787
Synthesis and anti-inflammatory activity of novel diarylheptanoids [5-hydroxy-1-phenyl-7-(pyridin-3-yl)-heptan-3-ones and 1-phenyl-7-(pyridin-3-yl)hept-4-en-3-ones] as inhibitors of tumor necrosis factor-α (TNF-α) production is described in the present article. The key reactions involve the formation of a β-hydroxyketone by the reaction of substituted 4-phenyl butan-2-ones with pyridine-3-carboxaldehyde in presence of LDA and the subsequent dehydration of the same to obtain the α,β-unsaturated ketones. Compounds 4i, 5b, 5d, and 5g significantly inhibit lipopolysaccharide (LPS)-induced TNF-α production from human peripheral blood mononuclear cells in a dose-dependent manner. Of note, the in vitro TNF-α inhibition potential of 5b and 5d is comparable to that of curcumin (a naturally occurring diarylheptanoid). Most importantly, oral administration of 4i, 5b, 5d, and 5g (each at 100 mg/kg) but not curcumin (at 100 mg/kg) significantly inhibits LPS-induced TNF-α production in BALB/c mice. Collectively, our findings indicate that these compounds may have potential therapeutic implications for TNF-α-mediated auto-immune/inflammatory disorders. 相似文献
92.
Reddy MV Shen YC Yang JS Hwang TL Bastow KF Qian K Lee KH Wu TS 《Bioorganic & medicinal chemistry》2011,19(6):1895-1906
A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC(50) values of 0.3 and 0.5 μM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 μM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI(50) values ranging from 0.70 to 13.10 μM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling. 相似文献
93.
Kamal A Reddy MK Ramaiah MJ Rajender Reddy JS Srikanth YV Dastagiri D Bharathi EV Pushpavalli SN Sarma P Pal-Bhadra M 《Bioorganic & medicinal chemistry》2011,19(8):2565-2581
A series of new estradiol linked pyrrolo[2,1-c][1,4]benzodiazepine (E(2)-PBD) conjugates (3a-f, 4a-f and 5a-f) with different linker architectures including a triazole moiety have been designed and synthesized. All the 18 compounds have been evaluated for their anticancer activity and it is observed that some of the compounds particularly 4c-e and 5c,d exhibited significant anticancer activity. The detailed biological aspects relating to the cell cycle effects and tubulin depolymerization activity have been examined with a view to understand the mechanism of action of these conjugates. Among all these conjugates, one of the compound 5c could be considered as the most effective compound particularly against MCF-7 breast cancer cell line. 相似文献
94.
Kumaran Sivagnanam Vijaya GS Raghavan Manesh Shah Robert L Hettich Nathan C Verberkmoes Mark G Lefsrud 《Proteome science》2011,9(1):1-14
Background
Cytokinin is a plant hormone that plays a crucial role in several processes of plant growth and development. In recent years, major breakthroughs have been achieved in the elucidation of the metabolism, the signal perception and transduction, as well as the biological functions of cytokinin. An important activity of cytokinin is the involvement in chloroplast development and function. Although this biological function has already been known for 50 years, the exact mechanisms remain elusive.Results
To elucidate the effects of altered endogenous cytokinin content on the structure and function of the chloroplasts, chloroplast subfractions (stroma and thylakoids) from transgenic Pssu-ipt and 35S:CKX1 tobacco (Nicotiana tabacum) plants with, respectively, elevated and reduced endogenous cytokinin content were analysed using two different 2-DE approaches. Firstly, thykaloids were analysed by blue-native polyacrylamide gel electrophoresis followed by SDS-PAGE (BN/SDS-PAGE). Image analysis of the gel spot pattern thus obtained from thylakoids showed no substantial differences between wild-type and transgenic tobacco plants. Secondly, a quantitative DIGE analysis of CHAPS soluble proteins derived from chloroplast subfractions indicated significant gel spot abundance differences in the stroma fraction. Upon identification by MALDI-TOF/TOF mass spectrometry, these proteins could be assigned to the Calvin-Benson cycle and photoprotective mechanisms.Conclusion
Taken together, presented proteomic data reveal that the constitutively altered cytokinin status of transgenic plants does not result in any qualitative changes in either stroma proteins or protein complexes of thylakoid membranes of fully developed chloroplasts, while few but significant quantitative differences are observed in stroma proteins. 相似文献95.
96.
Puligundla P Smogrovicova D Obulam VS Ko S 《Journal of industrial microbiology & biotechnology》2011,38(9):1133-1144
There have been numerous developments in ethanol fermentation technology since the beginning of the new millennium as ethanol
has become an immediate viable alternative to fast-depleting crude reserves as well as increasing concerns over environmental
pollution. Nowadays, although most research efforts are focused on the conversion of cheap cellulosic substrates to ethanol,
methods that are cost-competitive with gasoline production are still lacking. At the same time, the ethanol industry has engaged
in implementing potential energy-saving, productivity and efficiency-maximizing technologies in existing production methods
to become more viable. Very high gravity (VHG) fermentation is an emerging, versatile one among such technologies offering
great savings in process water and energy requirements through fermentation of higher concentrations of sugar substrate and,
therefore, increased final ethanol concentration in the medium. The technology also allows increased fermentation efficiency,
without major alterations to existing facilities, by efficient utilization of fermentor space and elimination of known losses.
This comprehensive research update on VHG technology is presented in two main sections, namely VHG brewing, wherein the effects
of nutrients supplementation, yeast pitching rate, flavour compound synthesis and foam stability under increased wort gravities
are discussed; and VHG bioethanol fermentation studies. In the latter section, aspects related to the role of osmoprotectants
and nutrients in yeast stress reduction, substrates utilized/tested so far, including saccharide (glucose, sucrose, molasses,
etc.) and starchy materials (wheat, corn, barley, oats, etc.), and mash viscosity issues in VHG bioethanol production are
detailed. Thereafter, topics common to both areas such as process optimization studies, mutants and gene level studies, immobilized
yeast applications, temperature effect, reserve carbohydrates profile in yeast, and economic aspects are discussed and future
prospects are summarized. 相似文献
97.
Kumar K Desai V Cheng L Khitrov M Grover D Satya RV Yu C Zavaljevski N Reifman J 《PloS one》2011,6(3):e17469
BACKGROUND: The annotation of genomes from next-generation sequencing platforms needs to be rapid, high-throughput, and fully integrated and automated. Although a few Web-based annotation services have recently become available, they may not be the best solution for researchers that need to annotate a large number of genomes, possibly including proprietary data, and store them locally for further analysis. To address this need, we developed a standalone software application, the Annotation of microbial Genome Sequences (AGeS) system, which incorporates publicly available and in-house-developed bioinformatics tools and databases, many of which are parallelized for high-throughput performance. METHODOLOGY: The AGeS system supports three main capabilities. The first is the storage of input contig sequences and the resulting annotation data in a central, customized database. The second is the annotation of microbial genomes using an integrated software pipeline, which first analyzes contigs from high-throughput sequencing by locating genomic regions that code for proteins, RNA, and other genomic elements through the Do-It-Yourself Annotation (DIYA) framework. The identified protein-coding regions are then functionally annotated using the in-house-developed Pipeline for Protein Annotation (PIPA). The third capability is the visualization of annotated sequences using GBrowse. To date, we have implemented these capabilities for bacterial genomes. AGeS was evaluated by comparing its genome annotations with those provided by three other methods. Our results indicate that the software tools integrated into AGeS provide annotations that are in general agreement with those provided by the compared methods. This is demonstrated by a >94% overlap in the number of identified genes, a significant number of identical annotated features, and a >90% agreement in enzyme function predictions. 相似文献
98.
Kiss DL Xu W Gopalan S Buzanowska K Wilczynska KM Rydel RE Kordula T 《Journal of neurochemistry》2005,92(4):730-738
Expression of alpha1antichymotrypsin (ACT) is significantly activated by interleukin-1 (IL-1) in human astrocytes; however, it is barely affected by IL-1 in hepatocytes. This tissue-specific regulation depends upon an enhancer that contains both nuclear factor kappaB (NF-kappaB) and activating protein 1 (AP-1) elements, and is also observed for an NF-kappaB reporter but not for an AP-1 reporter. We found efficient activation of NF-kappaB binding in both cell types; however, this binding was persistent in glial cells and only transient in hepatocytes. IL-1-activated NF-kappaB complexes consisted of p65 and p50, with p65 transiently phosphorylated on serine 536 in glial cells whereas more persistently in hepatic cells. Overexpression of p65 or constitutively active IKKbeta (inhibitor of NF-kappaB kinase beta) resulted in an efficient activation of the ACT reporter in hepatic cells, indicating that a specific mechanism exists in these cells terminating IL-1 signaling. IL-1 effectively induced the degradation of inhibitor of NF-kappaBalpha (IkBalpha) and IkBepsilon in both cell types but IkBbeta was not affected. However, IkBalpha was resynthesized much more rapidly in hepatic cells in comparison to glial cells. In addition, the initial levels of IkBalpha were much lower in glial cells. We propose that the tissue-specific regulation of the ACT gene expression by IL-1 is determined by different efficiencies of IkBalpha resynthesis in glial and hepatic cells. 相似文献
99.
Gopalan S Kasza A Xu W Kiss DL Wilczynska KM Rydel RE Kordula T 《Journal of neurochemistry》2005,94(3):763-773
The distal serpin subcluster contains genes encoding alpha1-antichymotrypsin (ACT), protein C inhibitor (PCI), kallistatin (KAL) and the KAL-like protein, which are expressed in hepatocytes, but only the act gene is expressed in astrocytes. We show here that the tissue-specific expression of these genes associates with astrocyte- and hepatocyte-specific chromatin structures. In hepatocytes, we identified 12 Dnase I-hypersensitive sites (DHSs) that were distributed throughout the entire subcluster, with the promoters of expressed genes accessible to restriction enzyme digestion. In astrocytes, only six DHSs were located exclusively in the 5' flanking region of the act gene, with its promoter also accessible to restriction enzyme digestion. The acetylation of histone H3 and H4 was found throughout the subcluster in both cell types but this acetylation did not correlate with the expression pattern of these serpin genes. Analysis of histone modifications at the promoters of the act and pci genes revealed that methylation of histone H3 on lysine 4 correlated with their expression pattern in both cell types. In addition, inhibition of methyltransferase activity resulted in suppression of ACT and PCI mRNA expression. We propose that lysine 4 methylation of histone H3 correlates with the tissue-specific expression pattern of these serpin genes. 相似文献
100.
HIV-1 within the CNS produces a neuroAIDS syndrome and may act as a reservoir for reinfection of the peripheral tissues. Study of how HIV-1 crosses the blood-brain barrier (BBB) has been hampered by the lack of nonprimate animal models. However, BBB transport of HIV-1 does not involve any of the known steps conferring species specificity, including binding to CD4 receptors. In vivo and in vitro studies show that HIV-1 and its glycoprotein coat, gp120, are taken up and transported across the BBB of the mouse. Here, we compared the ability of gp120 and HIV-1 to be taken up by isolated brain microvessels (IBM) freshly isolated from mice, from post-mortem human brain, and from mice that had been treated in a manner analogous to the human material (mouse post-mortem). Freshly isolated mouse IBM took up more gp120 and HIV-1 than the human or mouse post-mortem cells. We found no difference between the ability of mouse post-mortem and human IBM to take up either gp120 or HIV-1. Wheatgerm agglutinin has been previously shown to stimulate gp120 and HIV-1 uptake by the BBB; here, it stimulated the uptake of gp120 and of HIV-1 by both mouse post-mortem and human IBM, although stimulated uptake was greatest for fresh mouse IBM. These results show that the mouse can be used to study the initial phases of HIV-1 uptake by the BBB. 相似文献