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We investigated the effect of melanocortin 4 receptor (MC4) antagonists on food intake in mice. Food intake during the light phase was significantly increased by ICV administration of mixed MC3/MC4 antagonists (AgRP and SHU9119) or MC4 selective antagonist peptide [(Cyclo (1-5)[Suc-D-Nal-Arg-Trp-Lys]NH2] (MBP10) and the small molecule antagonists THP and NBI-30. Both mixed and selective antagonists significantly reversed anorexia induced by ICV administration of the MC4 agonist (c (1-6) HfRWK-NH2) and the cytokine IL-1beta. These findings provide pharmacological evidence that the MC4 receptor mediates the effects of melanocortin agonists and antagonists on food intake in mice, and support the idea that selective small molecule MC4 antagonists may be useful as therapeutics for cachexia. 相似文献
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E Wang Y Zhao A Monaco L Uccellini JM Kirkwood M Spyropoulou-Vlachou MC Panelli FM Marincola H Gogas 《PloS one》2012,7(7):e40805
Purpose
IFNa was the first cytokine to demonstrate anti-tumor activity in advanced melanoma. Despite the ability of high-dose IFNa reducing relapse and mortality by up to 33%, large majority of patients experience side effects and toxicity which outweigh the benefits. The current study attempts to identify genetic markers likely to be associated with benefit from IFN-a2b treatment and predictive for survival.Experimental design
We tested the association of variants in FOXP3 microsatellites, CTLA4 SNPs and HLA genotype in 284 melanoma patients and their association with prognosis and survival of melanoma patients who received IFNa adjuvant therapy.Results
Univariate survival analysis suggested that patients bearing either the DRB1*15 or HLA-Cw7 allele suffered worse OS while patients bearing either HLA-Cw6 or HLA-B44 enjoyed better OS. DRB1*15 positive patients suffered also worse RFS and conversely HLA-Cw6 positive patients had better RFS. Multivariate analysis revealed that a five-marker genotyping signature was prognostic of OS independent of disease stage. In the multivariate Cox regression model, HLA-B38 (p = 0.021), HLA-C15 (p = 0.025), HLA-C3 (p = 0.014), DRB1*15 (p = 0.005) and CT60*G/G (0.081) were significantly associated with OS with risk ratio of 0.097 (95% CI, 0.013–0.709), 0.387 (95% CI, 0.169–0.889), 0.449 (95% CI, 0.237–0.851), 1.948 (95% CI, 1.221–3.109) and 1.484 (95% IC, 0.953–2.312) respectively.Conclusion
These results suggest that gene polymorphisms relevant to a biological occurrence are more likely to be informative when studied in concert to address potential redundant or conflicting functions that may limit each gene individual contribution. The five markers identified here exemplify this concept though prospective validation in independent cohorts is needed. 相似文献4.
Pontillo J Wu D Ching B Hudson S Genicot MJ Gao Y Ewing T Fleck BA Gogas K Aparicio A Wang H Wen J Wade WS 《Bioorganic & medicinal chemistry letters》2008,18(23):6151-6155
The design synthesis and SAR of a series of chiral ring-constrained norepinephrine reuptake inhibitors with improved physicochemical properties is described. Typical compounds are potent (IC(50)s<10 nM), selective against the other monoamine transporters, weak CYP2D6 inhibitors (IC(50)s>1 microM) and stable to oxidation by human liver microsomes. In addition, the compounds exhibit a favorable polarity profile. 相似文献
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Hudson S Kiankarimi M Eccles W Mostofi YS Genicot MJ Dwight W Fleck BA Gogas K Wade WS 《Bioorganic & medicinal chemistry letters》2008,18(16):4495-4498
The design, synthesis and SAR of a series of heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. As racemates, the best compounds compare favorably with atomoxetine (IC(50)'s<10 nM) in potency at the transporter. 相似文献
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Dilek Gogas Yavuz Belgin Kü?ükkaya H. ?nder Ers?z A. Süha Yal?in Kaya Emerk Sema Akalin 《Experimental diabetes research》2002,3(2):145-151
Nonenzymatic glycation of tissue and plasma
proteins may stimulate the production of oxidant
and carbonyl stress in diabetes. The aim
of this study was to evaluate the effects of
aminoguanidine (AG) on lipid peroxidation,
protein oxidation and nitric oxide (NO) release
in diabetic rat kidneys. After induction of diabetes
with streptozotocin, female Wistar rats
were divided into 2 groups. Group DAG (n=9)
rats were given AG hydrogen carbonate (1 g/L)
in drinking water and group D (n=8) was diabetic
control rats given only tap water. Group
H (n=8) was followed as healthy controls. At
the end of an 8 week period, NO release, lipid
and protein oxidation were determined in kidney
tissues. NO release was significantly lower
in diabetic rats compared with healthy controls
(p<0.05). Lipid peroxidation was significantly
high in group D (3.9 ± 0.3 nmol MDA/g tissue)
compared with the group DAG (2.6 ± 0.1 nmol
MDA/g tissue, p<0.01) and group H (2.4 ± 0.2
nmol MDA/g tissue). Protein oxidation was
significantly higher in diabetics than healthy
controls (563.8 ± 23.9, 655.8 ± 7.2 , 431.5 ±
8.8 mmol carbonyl / g tissue for group DAG, D
and H, respectively, p< 0.05). A positive correlation
between albuminuria and thiobarbituric
acid reactive substance (TBARS) levels (r= 0.54,p<0.005) and carbonyl content (r=0.70,
p<0.0005) in kidney homogenate were
observed.
Although AG treatment had no effect on NO
release, it significantly decreased lipid peroxidation
in diabetic rat cortices. Consequently
increased lipid peroxidation -as well as- protein
oxidation could be involved in the pathogenesis
of diabetic albuminuria. 相似文献
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Eleni Timotheadou Konstantine T. Kalogeras Georgia-Angeliki Koliou Ralph M. Wirtz Flora Zagouri Angelos Koutras Elke Veltrup Christos Christodoulou George Pentheroudakis Aris Tsiftsoglou Pavlos Papakostas Gerasimos Aravantinos Vasilios Venizelos Dimitrios Pectasides Paris Kosmidis Charisios Karanikiotis Christos Markopoulos Helen Gogas George Fountzilas 《Translational oncology》2017,10(4):589-598
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低温对植物叶片中超氧物歧化酶、过氧化氢酶和过氧化氢水平的影响 总被引:10,自引:0,他引:10
番茄和鸡蛋果叶片中可提取的SOD活性不受低温的影响。在电泳谱带上SOD主同工酶带被氰化物而不被低温抑制,次同工酶带在低温下不稳定,且活性很低,它的变化不影响总的SOD活性。一些冷敏感植物叶片中CAT活性被低温抑制,而H_2O_3水平在低温下稳定或有增加,这可能使毒性更强的羟基离子(OH·)易于形成。 相似文献
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