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111.
112.
Phenotypic and functional effects of heat shock protein 90 inhibition on dendritic cell 总被引:1,自引:0,他引:1
Bae J Mitsiades C Tai YT Bertheau R Shammas M Batchu RB Li C Catley L Prabhala R Anderson KC Munshi NC 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):7730-7737
The 90-kDa heat shock protein (Hsp90) plays an important role in conformational regulation of cellular proteins and thereby cellular signaling and function. As Hsp90 is considered a key component of immune function and its inhibition has become an important target for cancer therapy, we here evaluated the role of Hsp90 in human dendritic cell (DC) phenotype and function. Hsp90 inhibition significantly decreased cell surface expression of costimulatory (CD40, CD80, CD86), maturation (CD83), and MHC (HLA-A, B, C and HLA-DP, DQ, DR) markers in immature DC and mature DC and was associated with down-regulation of both RNA and intracellular protein expression. Importantly, Hsp90 inhibition significantly inhibited DC function. It decreased Ag uptake, processing, and presentation by immature DC, leading to reduced T cell proliferation in response to tetanus toxoid as a recall Ag. It also decreased the ability of mature DC to present Ag to T cells and secrete IL-12 as well as induce IFN-gamma secretion by allogeneic T cells. These data therefore demonstrate that Hsp90-mediated protein folding is required for DC function and, conversely, Hsp90 inhibition disrupts the DC function of significant relevance in the setting of clinical trials evaluating novel Hsp90 inhibitor therapy in cancer. 相似文献
113.
Kaur K Patel SR Patil P Jain M Khan SI Jacob MR Ganesan S Tekwani BL Jain R 《Bioorganic & medicinal chemistry》2007,15(2):915-930
We report the synthesis, in vitro antiprotozoal (against Plasmodium and Leishmania), antimicrobial, cytotoxicity (Vero and MetHb-producing properties), and in vivo antimalarial activities of two series of 8-quinolinamines. N1-{4-[2-(tert-Butyl)-6-methoxy-8-quinolylamino]pentyl}-(2S/2R)-2-aminosubstitutedamides (21-33) and N1-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2S/2R)-2-aminosubstitutedamides (51-63) were synthesized in six steps from 6-methoxy-8-nitroquinoline and 4-methoxy-2-nitro-5-pentyloxyaniline, respectively. Several analogs displayed promising antimalarial activity in vitro against Plasmodium falciparum D6 (chloroquine-sensitive) and W2 (chloroquine-resistant) clones with high selectivity indices versus mammalian cells. The most promising analogs (21-24) also displayed potent antimalarial activity in vivo in a Plasmodium berghei-infected mouse model. Most interestingly, many analogs exhibited promising in vitro antileishmanial activity against Leishmania donovani promastigotes, and antimicrobial activities against a panel of pathogenic bacteria and fungi. Several analogs, notably 21-24, 26-32, and 60, showed less MetHb formation compared to primaquine indicating the potential of these compounds in 8-quinolinamine-based antimalarial drug development. 相似文献
114.
Aruliah Rajasekar Thambidurai Ganesh Babu Sundaram Maruthamuthu Shunmugiah Thevar Karutha Pandian Sidhan Mohanan Narayanan Palaniswamy 《World journal of microbiology & biotechnology》2007,23(8):1065-1074
A facultative anaerobic species Serratia marcescens ACE2 isolated from the corrosion products of a diesel-transporting pipeline in North West India was identified by 16S rDNA
sequence analysis. The role of Serratia marcesens ACE2 on biodegradation of commercial corrosion inhibitor (CCI) and its influence on the corrosion of API 5LX steel has been
enlightened. The degrading strain ACE2 is involved in the process of corrosion of steel API 5LX and also utilizes the inhibitor
as organic source. The quantitative biodegradation efficiency of corrosion inhibitor was 58%, which was calculated by gas
chromatography mass spectrum analysis. The effect of CCI on the growth of bacteria and its corrosion inhibition efficiency
were investigated. Additionally, the role of this bacterium in corrosion of steel has been investigated by powder X-ray diffractometer
(XRD) and scanning electron microscope studies. The presence of high-intensity ferric oxides and manganese oxides noticed
from the XRD indicates that ACE2 enhances the corrosion process in presence of inhibitor as a carbon source. This basic study
will be useful for the development of new approaches for the detection, monitoring and control of microbial corrosion in petroleum
product pipelines. 相似文献
115.
Influence of recirculation on the performance of anaerobic sequencing batch biofilm reactor (AnSBBR) was studied in the process of treating hypersaline (total dissolved inorganic solids (TDIS) approximately 26 g/l) and low biodegradable (BOD/COD approximately 0.3) composite chemical wastewater. Significant enhancement in the substrate removal efficiency and biogas yield was observed after introducing the recirculation to the system. Maximum efficiency (COD removal efficiency - 51%; SDR - 3.14 kg COD/cum-day) was observed at recirculation to feed (R/F) ratio of 2 (OLR - 6.15 kg C OD/cum-day; HLR - 2.30 cum (liquid)/cum day; UFV(A) - 0.023 m/h). Subsequent increase of R/F to 3 (OLR - 6.15 kg COD/cum-day; HLR - 3.07cum (liquid)/cum-day; UFV(A) - 0.035 m/h) resulted in reduction in COD removal efficiency (32%; SDR - 1.97 kg COD/cum-day). The enhanced performance of the system due to the introduction of recirculation was attributed to the improvement in the mass transfer between the substrate present in the bulk liquid and the attached biofilm. The hydrodynamic behavior due to recirculation mode of operation reduced the concentration gradient (substrate inhibition) of substrate and reaction by-products (VFA) resulting in mixed flow conditions. 相似文献
116.
Dharmu I Ramamurty N Kannan R Babu M 《In vitro cellular & developmental biology. Animal》2007,43(8-9):306-314
The hemolymph-derived achatininH (lectin) from Achatina fulica showed a marked cytotoxic effect on MCF7, a human mammary carcinoma cell line. IC50 values as measured by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay for achatininH ranged from 6 to 10 μg/ml in the MCF7 cells. MCF7 cells showed significant morphological changes leading to cell death. The
above cell death was observed after 48 h of treatment with 8 μg/ml when compared to untreated cells. Alterations in the tumor
marker enzymes, as well as in antioxidant enzymes, were observed after achatininH treatment. The specificity and purity of the achatininH was confirmed by the Western blot assay. AchatininH binding to MCF7 cells was detected by anti-achatininH, and visualization of the achatininH binding sites on confluent MCF7 cells was confirmed by flourescein isothiocyanate conjugated secondary antibody. MCF7-treated
cells fluoresced, indicating the presence of achatininH binding sites. Fluorescence-activated cell sorting analysis of the cell cycle showed a significant increase in S-phase in
MCF7 cells after 48 h of achatininH treatment. The cells were arrested in G2/M phase of the cell cycle after 48 h with significant changes in cell viability. Cellular damage was confirmed by agarose
gel electrophoresis with the characteristic appearance of a DNA streak in treated MCF7 cells indicating the ongoing apoptosis.
An erratum to this article can be found at 相似文献
117.
Cinnamaldehyde—A potential antidiabetic agent 总被引:1,自引:0,他引:1
Cinnamonum zeylanicum (cinnamon) is widely used in traditional system of medicine to treat diabetes in India. The present study was carried out to isolate and identify the putative antidiabetic compounds based on bioassay-guided fractionation; the compound identified decreased the plasma glucose levels. The active compound was purified by repeat column and structure of cinnamaldehyde was determined on the basis of chemical and physiochemical evidence. The LD(50) value of cinnamaldehyde was determined as 1850+/-37 mg/kg bw. Cinnamaldehyde was administered at different doses (5, 10 and 20 mg/kg bw) for 45 days to streptozotocin (STZ) (60 mg/kg bw)-induced male diabetic wistar rats. It was found that plasma glucose concentration was significantly (p<0.05) decreased in a dose-dependent manner (63.29%) compared to the control. In addition, oral administration of cinnamaldehyde (20 mg/kg bw) significantly decreased glycosylated hemoglobin (HbA(1C)), serum total cholesterol, triglyceride levels and at the same time markedly increased plasma insulin, hepatic glycogen and high-density lipoprotein-cholesterol levels. Also cinnamaldehyde restored the altered plasma enzyme (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase) levels to near normal. Administration of glibenclamide, a reference drug (0.6 mg/kg bw) also produced a significant (p<0.05) reduction in blood glucose concentration in STZ-induced diabetic rats. The results of this experimental study indicate that cinnamaldehyde possesses hypoglycemic and hypolipidemic effects in STZ-induced diabetic rats. 相似文献
118.
A novel conotoxin pl14a containing 25 amino acid residues with an amidated C-terminus from vermivorous cone snail, Conus planorbis belongs to J-conotoxin superfamily and this is the first conotoxin, which inhibits both nicotinic acetylcholine receptor subtypes and Kv1.6 channel. We have attempted through bioinformatics approaches to elucidate the extent of specificity of pl14a towards Kv1 channel subtypes (Kv1.1-Kv1.6). Our work provides rationale for the relatively high specificity and binding mode of pl14a to Kv1.6 channel. The pl14a peptide contains two types of structural elements, namely the putative dyad (Lys18 and Tyr19) and basic residue ring constituted of arginine residues. We have carried out in silico docking studies so as to assess the contribution of one or combination of both structural elements of pl14a in blocking of Kv1.6 channel. For this purpose, we have built by homology modelling, the theoretical 3D structure of Kv1.6 channel based on the available crystal structure of mammalian shaker Kv1.2 channel. Docking studies suggest that positively charged residues ring may be involved in the blocking mechanism of Kv1.6 channel. The models suggest that the peptide interacts with negatively charged extracellular loops and pore-mouth of the potassium channel and blocks the channel by covering the pore as a lid, akin to previously proposed blocking mechanism of kappaM-conotoxin RIIIK from Conus radiatus to Tsha1 potassium channel. The newly detected pharmacophore for pl14a interacting with Kv1.6 channel provides a pointer to experimental work to validate the observations made here. Based on differences in the number and distribution of the positively-charged residues in other conopeptides from the J-superfamily, we hypothesize different selectivity profiles against subtypes of the potassium channels for these conopeptides. 相似文献
119.
Umemoto T Hrdlicka PJ Babu BR Wengel J 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1261-1263
A dual-probe containing pyrenylmethyl amino-LNA has been developed for sensitive mismatch detection. While hybridization with complementary DNA/RNA results in very strong excimer signals, exposure to singly mismatched DNA/RNA targets results in significantly decreased excimer emission. 相似文献
120.