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排序方式: 共有106条查询结果,搜索用时 10 毫秒
1.
Venkataraman B.V. Ravishankar H.N. Rao Aparna V.S. Kalyani P. Sharada G. Namboodiri K. Gahor B. Ramasarma T. 《Molecular and cellular biochemistry》1997,169(1-2):27-36
Decavanadate, an inorganic polymer of vanadate, produced contraction of rat aortic rings at a relatively high concentration compared to phenylephrine, an agonist of -adrenergic receptor. This effect was blocked by two known a-adrenergic receptor antagonists, prazosin and phenoxybenzamine. Decavanadate, formed by possible dimerization of V5 under acid conditions, possessed a structural feature of two pairs of unshared oxygen atoms at a distance of 3.12 Å, not found in its constituents of V4 or V5. A structural motif of O..O..O using such oxygen atoms is recognized in decavanadate. This matches with a similar motif of N..O..O that uses the essential amino and hydroxyl groups of the side-chain and the m-hydroxyl group in trans-b form of noradrenaline. The interaction of such a structural motif with the membrane receptor is likely to be the basis of the unusual noradrenaline-mimic action of decavanadate. 相似文献
2.
Mokkapati S Fleger-Weckmann A Bechtel M Koch M Breitkreutz D Mayer U Smyth N Nischt R 《The Journal of biological chemistry》2011,286(3):1911-1918
The nidogen-laminin interaction is proposed to play a key role in basement membrane (BM) assembly. However, though there are similarities, the phenotypes in mice lacking nidogen 1 and 2 (nidogen double null) differ to those of mice lacking the nidogen binding module (γ1III4) of the laminin γ1 chain. This indicates different cell- and tissue-specific functions for nidogens and their interaction with laminin and poses the question of whether the phenotypes in nidogen double null mice are caused by the loss of the laminin-nidogen interaction or rather by other unknown nidogen functions. To investigate this, we analyzed BMs, in particular those in the skin of mice lacking the nidogen binding module. In contrast to nidogen double null mice, all skin BMs in γ1III4-deficient mice appeared normal. Furthermore, although nidogen 1 deposition was strongly reduced, nidogen 2 appeared unchanged. Mice with additional deletion of the laminin γ3 chain, which contains a γ1-like nidogen binding module, showed a further reduction of nidogen 1 in the dermoepidermal BM; however, this again did not affect nidogen 2. This demonstrates that in vivo only nidogen 1 deposition is critically dependent on the nidogen binding modules of the laminin γ1 and γ3 chains, whereas nidogen 2 is independently recruited either by binding to an alternative site on laminin or to other BM proteins. 相似文献
3.
4.
Satyanarayana S Sekhar JR Kumar KE Shannika LB Rajanna B Rajanna S 《Molecular and cellular biochemistry》2006,283(1-2):123-127
Oxidative stress is involved in diabetes mellitus and its complications. Since diabetes is a stress-related disorder, supplementation
with antioxidants may improve the condition. The purpose of this study is to know the effect of oral administration of selenium
on blood glucose and its influence on gliclazide induced hypoglycaemia/antihyperglycaemia in normal and alloxan-induced diabetic
rats. Albino rats of either sex were divided into three groups of six each. Group-I/II/III were treated with selenium 1/2
TD (0.9 μg/200 g rat)/TD (1.8 μg/200 g rat)/2TD (3.6 μg/200 g rat), respectively. Later group II was treated with gliclazide
TD (1.44 mg/200 g rat)/selenium TD + gliclazide TD with a washout period of 1 week between the treatments. Diabetes was induced
by alloxan monohydrate 100 mg/kg body weight i.p. A group of six rats showing fasting blood glucose levels ranging from 175–250
mg/dl were selected for the study. Rats were treated with selenium TD, gliclazide TD and selenium TD + gliclazide TD with
a washout period of 1 week between the treatments. Selenium 1/2 TD and TD produced hypoglycaemia while 2TD produced hyperglycaemia.
The combination of selenium TD with gliclazide TD, significantly enhanced the glucose lowering effect of gliclazide in normal
and diabetic rats. 相似文献
5.
6.
Marlys Hammond David G. Washburn Tram H. Hoang Sharada Manns James S. Frazee Hiroko Nakamura Jaclyn R. Patterson Walter Trizna Charlene Wu Leonard M. Azzarano Rakesh Nagilla Melanie Nord Rebecca Trejo Martha S. Head Baoguang Zhao Angela M. Smallwood Kendra Hightower Nicholas J. Laping Christine G. Schnackenberg Scott K. Thompson 《Bioorganic & medicinal chemistry letters》2009,19(15):4441-4445
The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. 相似文献
7.
Informed Consent in Health Research: Challenges and Barriers in Low‐and Middle‐Income Countries with Specific Reference to Nepal 下载免费PDF全文
Pramod R. Regmi Nirmal Aryal Om Kurmi Puspa Raj Pant Edwin van Teijlingen Sharada P. Wasti 《Developing world bioethics》2017,17(2):84-89
Obtaining ‘informed consent’ from every individual participant involved in health research is a mandatory ethical practice. Informed consent is a process whereby potential participants are genuinely informed about their role, risk and rights before they are enrolled in the study. Thus, ethics committees in most countries require ‘informed consent form’ as part of an ethics application which is reviewed before granting research ethics approval. Despite a significant increase in health research activity in low‐and middle‐income countries (LMICs) in recent years, only limited work has been done to address ethical concerns. Most ethics committees in LMICs lack the authority and/or the capacity to monitor research in the field. This is important since not all research, particularly in LMICs region, complies with ethical principles, sometimes this is inadvertently or due to a lack of awareness of their importance in assuring proper research governance. With several examples from Nepal, this paper reflects on the steps required to obtain informed consents and highlights some of the major challenges and barriers to seeking informed consent from research participants. At the end of this paper, we also offer some recommendations around how can we can promote and implement optimal informed consent taking process. We believe that paper is useful for researchers and members of ethical review boards in highlighting key issues around informed consent. 相似文献
8.
Kendall JD O'Connor PD Marshall AJ Frédérick R Marshall ES Lill CL Lee WJ Kolekar S Chao M Malik A Yu S Chaussade C Buchanan C Rewcastle GW Baguley BC Flanagan JU Jamieson SM Denny WA Shepherd PR 《Bioorganic & medicinal chemistry》2012,20(1):69-85
We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110α isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a]pyridine ring system, and found compound 5x to be a particularly potent example (p110α IC(50) 0.9nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model. 相似文献
9.
Khanh B. Tran Gregory Gimenez Peter Tsai Sharada Kolekar Euan J. Rodger Aniruddha Chatterjee Anower Jabed Jen‐Hsing Shih Wayne R. Joseph Elaine S. Marshall Qian Wang Cristin G. Print Michael R. Eccles Bruce C. Baguley Peter R. Shepherd 《Pigment cell & melanoma research》2021,34(1):136-143
Melanoma is a disease associated with a very high mutation burden and thus the possibility of a diverse range of oncogenic mechanisms that allow it to evade therapeutic interventions and the immune system. Here, we describe the characterization of a panel of 102 cell lines from metastatic melanomas (the NZM lines), including using whole‐exome and RNA sequencing to analyse genetic variants and gene expression changes in a subset of this panel. Lines possessing all major melanoma genotypes were identified, and hierarchical clustering of gene expression profiles revealed four broad subgroups of cell lines. Immunogenotyping identified a range of HLA haplotypes as well as expression of neoantigens and cancer–testis antigens in the lines. Together, these characteristics make the NZM panel a valuable resource for cell‐based, immunological and xenograft studies to better understand the diversity of melanoma biology and the responses of melanoma to therapeutic interventions. 相似文献
10.
Cushing TD Baichwal V Berry K Billedeau R Bordunov V Broka C Browner MF Cardozo M Cheng P Clark D Dalrymple S DeGraffenreid M Gill A Hao X Hawley RC He X Labadie SS Labelle M Lehel C Lu PP McIntosh J Miao S Parast C Shin Y Sjogren EB Smith ML Talamas FX Tonn G Walker KM Walker NP Wesche H Whitehead C Wright M Jaen JC 《Bioorganic & medicinal chemistry letters》2011,21(1):423-426
A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with submicromolar potency in a HWB assay and efficacy in a CIA mouse model. 相似文献