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111.
Yang Liu Rebecca J. Whelan Bikash R. Pattnaik Kai Ludwig Enkateswar Subudhi Helen Rowland Nick Claussen Noah Zucker Shitanshu Uppal David M. Kushner Mildred Felder Manish S. Patankar Arvinder Kapur 《PloS one》2012,7(12)
Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer. Here, we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger (SDGE) are potent inhibitors of proliferation of endometrial cancer cells. SDGE, isolated from six different batches of ginger rhizomes, consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC50 of 1.25 µg/ml. SDGE also enhanced the anti-proliferative effect of radiation and cisplatin. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3. GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE, with the isomers neral and geranial constituting 30–40%. Citral, a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC50 10 µM (2.3 µg/ml). Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells. SDGE was more effective in inducing cancer cell death than citral, suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death. SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20–40% decrease in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE. This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax. Inhibitor of p53, pifithrin-α, attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53neg SKOV-3 cells. Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer. 相似文献
112.
Johnson RJ West CE Swaih AM Folwell BD Smith BE Rowland SJ Whitby C 《Environmental microbiology》2012,14(4):872-882
Naphthenic acids (NAs) are complex mixtures of carboxylic acids found in weathered crude oils and oil sands, and are toxic, corrosive and persistent. However, little is known about the microorganisms and mechanisms involved in NA degradation. We isolated a sediment bacterium (designated strain IS2.3), with 100% 16S rRNA gene sequence identity to Mycobacterium aurum, which degraded synthetic NAs (4'-n-butylphenyl)-4-butanoic acid (n-BPBA) and (4'-t-butylphenyl)-4-butanoic acid (t-BPBA). n-BPBA was readily oxidized with almost complete degradation (96.8% ± 0.3) compared with t-BPBA (77.8% ± 3.7 degraded) by day 49. Cell counts increased fourfold by day 14 but decreased after day 14 for both n- and t-BPBA. At day 14, (4'-butylphenyl)ethanoic acid (BPEA) metabolites were detected. Additional metabolites produced during t-BPBA degradation were identified by mass spectrometry of derivatives as (4'-carboxy-t-butylphenyl)-4-butanoic acid and (4'-carboxy-t-butylphenyl)ethanoic acid; suggesting that strain IS2.3 used omega oxidation of t-BPEA to oxidize the tert-butyl side-chain to produce (4'-carboxy-t-butylphenyl)ethanoic acid, as the primary route for biodegradation. However, strain IS2.3 also produced this metabolite through initial omega oxidation of the tert-butyl side-chain of t-BPBA, followed by beta-oxidation of the alkanoic acid side-chain. In conclusion, an isolate belonging to the genus Mycobacterium degraded highly branched aromatic NAs via two different pathways. 相似文献
113.
Li Z Zharikova A Bastian J Esperon L Hebert N Mathes C Rowland NE Peris J 《Journal of neurochemistry》2008,106(1):170-181
Capillary electrophoresis coupled with laser-induced fluorescence detection (CE-LIF) provides 15-s temporal resolution of amino acid levels in microdialysate, which, for the first time, allows almost real time measurement of changes during episodes of behavior. We trained Sprague-Dawley rats to self-administer either 10% ethanol-containing gelatin or non-alcoholic gelatin in a typical operant chamber. After rats reached stable daily levels of responding, microdialysis probes were inserted into nucleus accumbens and samples were collected before, during and after operant sessions with on-line analysis via CE-LIF. During the first 15 min of the operant session, there was a significant increase in taurine that correlated with the amount of ethanol consumed ( R 2 = 0.81) but no change in rats responding for plain gel. There were large, consistent increases in glycine in both the ethanol and plain gel groups which correlated with the amount of gel consumed. A smaller increase was observed in rats with free non-operant access to plain gel compared to the increase seen with the same amount of gel consumed under operant conditions. When rats were given a time out after each delivery of gel in the operant protocol, the greatest increase of glycine was obtained with the longest time out period. Thus, increases in glycine in nucleus accumbens appear to be related to anticipation of reinforcement. 相似文献
114.
Clarke B Demont E Dingwall C Dunsdon R Faller A Hawkins J Hussain I MacPherson D Maile G Matico R Milner P Mosley J Naylor A O'Brien A Redshaw S Riddell D Rowland P Soleil V Smith KJ Stanway S Stemp G Sweitzer S Theobald P Vesey D Walter DS Ward J Wayne G 《Bioorganic & medicinal chemistry letters》2008,18(3):1017-1021
This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures. 相似文献
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The mosquito Anopheles stephensi is an important malaria vector in India, Pakistan, Iran and Afghanistan. Differences in egg morphology and chromosomal characters have been described between urban and rural forms of this mosquito but the population genetic structure remains unclear. In India this species is mainly urban, rural populations are largely zoophilic and not thought to transmit malaria. In eastern Afghanistan and the Punjab and Northwest Frontier Province, Pakistan, it is the major malaria vector. We have developed primers for 16 microsatellite loci to assist in defining the population structure and epidemiological importance of this mosquito. 相似文献
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119.
By the end of June 1969 home nurses in Bristol were attached to 18 general practices caring for about 137,000 patients, or about one-third of the city''s population. Attachment was associated with an increase by about one-third in the number of patients referred by general practitioners for home nursing. Additional benefits derived from attachment during the nine months from January to September 1969 were 2,047 items of service performed by nurses in general practitioners'' surgeries, 65 home visits to patients who were not receiving domiciliary nursing care, improved communications between general practitioners and nurses, and opportunities for both doctors and nurses to widen their fields of work. The travelling expenses paid to Bristol''s nurses increased by 9·5%.It is suggested that the benefits to patients, doctors, and nurses of attachment far outweigh the costs and that there is scope for extending the role of the attached nurse in the surgery and in home visiting. 相似文献
120.