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31.
苦瓜的营养价值、化学成分以及药理作用研究进展 总被引:1,自引:0,他引:1
本文总结了半个多世纪来国内外学者对苦瓜的研究,为苦瓜进一步开发提供了借鉴。 相似文献
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Bo Tan Sucai Dong Robert L. Shepard Lisa Kays Kenneth D. Roth Sandaruwan Geeganage Ming-Shang Kuo Genshi Zhao 《The Journal of biological chemistry》2015,290(25):15812-15824
Nicotinamide phosphoribosyltransferase (NAMPT) has been extensively studied due to its essential role in NAD+ biosynthesis in cancer cells and the prospect of developing novel therapeutics. To understand how NAMPT regulates cellular metabolism, we have shown that the treatment with FK866, a specific NAMPT inhibitor, leads to attenuation of glycolysis by blocking the glyceraldehyde 3-phosphate dehydrogenase step (Tan, B., Young, D. A., Lu, Z. H., Wang, T., Meier, T. I., Shepard, R. L., Roth, K., Zhai, Y., Huss, K., Kuo, M. S., Gillig, J., Parthasarathy, S., Burkholder, T. P., Smith, M. C., Geeganage, S., and Zhao, G. (2013) Pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT), an enzyme essential for NAD+ biosynthesis, in human cancer cells: metabolic basis and potential clinical implications. J. Biol. Chem. 288, 3500–3511). Due to technical limitations, we failed to separate isotopomers of phosphorylated sugars. In this study, we developed an enabling LC-MS methodology. Using this, we confirmed the previous findings and also showed that NAMPT inhibition led to accumulation of fructose 1-phosphate and sedoheptulose 1-phosphate but not glucose 6-phosphate, fructose 6-phosphate, and sedoheptulose 7-phosphate as previously thought. To investigate the metabolic basis of the metabolite formation, we carried out biochemical and cellular studies and established the following. First, glucose-labeling studies indicated that fructose 1-phosphate was derived from dihydroxyacetone phosphate and glyceraldehyde, and sedoheptulose 1-phosphate was derived from dihydroxyacetone phosphate and erythrose via an aldolase reaction. Second, biochemical studies showed that aldolase indeed catalyzed these reactions. Third, glyceraldehyde- and erythrose-labeling studies showed increased incorporation of corresponding labels into fructose 1-phosphate and sedoheptulose 1-phosphate in FK866-treated cells. Fourth, NAMPT inhibition led to increased glyceraldehyde and erythrose levels in the cell. Finally, glucose-labeling studies showed accumulated fructose 1,6-bisphosphate in FK866-treated cells mainly derived from dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Taken together, this study shows that NAMPT inhibition leads to attenuation of glycolysis, resulting in further perturbation of carbohydrate metabolism in cancer cells. The potential clinical implications of these findings are also discussed. 相似文献
34.
Carleer J Karres J 《Birth defects research. Part B, Developmental and reproductive toxicology》2011,92(4):254-260
During the workshop organized by ILSI/HESI on May 5-6, 2010 on the value of juvenile animal toxicity studies, the implementation of the European Pediatric Regulation and in particular the review process of the nonclinical part of the Pediatric Investigation Plan (PIP) were described. A PIP is intended to outline the development of a medicinal product in the pediatric population (i.e. quality, safety, efficacy of the medicine and timing of studies); it is reviewed and agreed by the Pediatric Committee (PDCO) of the European Medicines Agency (EMA). The Nonclinical Working Group (NcWG) supports the PDCO in the review process of the nonclinical part of a PIP and is composed of members from the PDCO, the EMA Safety Working Party, additional experts from national competent authorities and the FDA. This article summarizes the NcWG review process and outcomes of 97 approved or ongoing PIPs, from the establishment of the NcWG in November 2008 to May 2010, as presented during the workshop. Juvenile animal studies were proposed by the applicant in 33% or required by the NcWG in 26% of the PIPs. The requirements were mainly motivated by concerns regarding potential developmental toxicities, in view of the young age of the pediatric population to be investigated, the lack of knowledge concerning the maturation of the pharmacological target, the lack of sufficient (non)clinical data, observed toxicities in the adult (non)clinical studies and the long duration of the intended treatments. Most juvenile animal studies were in the therapeutic areas of oncology, infectious diseases and endocrinology. In about 14% of the PIPs submitted, the NcWG requested either justifications of, or amendments to the study designs proposed by the applicants (e.g. justification of endpoints, study duration, species selection and timing with regards to clinical pediatric studies). Generally, only one species was selected or proposed for the juvenile studies, the rat being the most prevalent. The number of juvenile studies initially proposed by the applicant plus those requested by the NcWG was higher than the number of studies included in the "key binding elements" of the PIP opinions. This apparent discrepancy was mainly due to additional information or justifications submitted by the applicant during the clock stop. It was noted that the PIPs initially submitted often lacked information relevant to the nonclinical evaluation. Therefore, during the workshop, the need to provide scientifically based justifications when no juvenile animal studies are proposed in the initial PIP submission was stressed. 相似文献
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目的:通过研究GX1-rmhTNFα对动物重要生命功能的影响,观察其主要药效学以外的药理作用,为临床研究和安全用药提供信息。方法:分别取大鼠、小鼠肌肉注射,测试GX1-rmhTNFα对动物中枢神经系统、心血管系统、呼吸系统的影响。结果:GX1-rmhTNFα三个剂量组对动物中枢神经系统,呼吸系统,心血管系统无明显影响,与生理盐水对照组比较P〉0.05。结论:在本实验中,GX1-rmhTNFα对小鼠的中枢神经系统无明显影响,对大鼠呼吸系统,心血管系统无显著性影响,提示其不良反应小。 相似文献
36.
Yu. V. Vakhitova R. S. Yamidanov V. A. Vakhitov S. B. Seredenin 《Molecular Biology》2005,39(2):244-252
The Atlas Rat cDNA Expression Array (BD Biosciences, United States) has been used to analyze changes in the expression of 588 genes in rat brain cells in response to a single administration of Ladasten, a 2-aminoadamantane derivative that has psychostimulating and anxiolytic effects. The analysis of hybridization on macroarrays, confirmed by the results of real-time quantitative RT-PCR, has demonstrated that Ladasten alters the expression of 12 genes in the rat brain. The GAT3 and CARBH genes are presumed to be pharmacologically important targets of Ladasten. The changes in their activity explain the mechanisms of the anxiolytic and mood-stabilizing effects of the drug. Ladasten has been shown to induce the genes whose products are involved in various signal pathways (APC, Rb, PKCIP, and PMCA), as well as the genes of cytoskeletal proteins (Tub1 and actin), synaptic proteins (SynIA&IB and PLP), and enzymes (Gapdh and NSE). The proteins encoded by these genes are presumably involved in compensatory and/or neuroplastic adaptation to the effects of Ladasten.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 276–285.Original Russian Text Copyright © 2005 by Vakhitova, Yamidanov, Vakhitov, Seredenin. 相似文献
37.
Mertens I Meeusen T Janssen T Nachman R Schoofs L 《Biochemical and biophysical research communications》2005,330(3):967-974
Two alternatively spliced Caenorhabditis elegans G protein-coupled receptors, T19F4.1a and T19F4.1b, were cloned and functionally characterized. The T19F4.1b receptor protein is 30 amino acids longer than T19F4.1a, and the difference in amino acid constitution is exclusively conferred to the intracellular C-terminal region, suggesting a potential difference in G protein-coupling specificity. Following cloning of the receptor cDNAs into the pcDNA3 vector and stable or transient transfection into Chinese hamster ovary cells, the aequorin bioluminescence/Ca2+ assay was used to investigate receptor activation. This is the first report of the construction of a cell line stably expressing a C. elegans neuropeptide receptor. Our experiments identified both receptors as being cognate receptors for two FMRFamide-related peptides encoded by the flp-2 precursor: SPREPIRFamide (FLP2-A) and LRGEPIRFamide (FLP2-B). Pharmacological profiling using truncated forms of FLP2-A and -B revealed that the active core of both peptides is EPIRFamide. Screening of peptides encoded by other flps did not result in a significant activation of the receptor. In contrast to other C. elegans receptors tested in heterologous expression systems, the functional activation of both T19F4.1a and T19F4.1b was not temperature-dependent. Screening in cells lacking the promiscuous Galpha16 suggests that T19F4.1a and b are both linked to the Gq pathway. 相似文献
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Das A Pushparaj C Bahí N Sorolla A Herreros J Pamplona R Vilella R Matias-Guiu X Martí RM Cantí C 《Pigment cell & melanoma research》2012,25(2):200-212
The expression of voltage-gated calcium channels (VGCCs) has not been reported previously in melanoma cells in spite of increasing evidence of a role of VGCCs in tumorigenesis and tumour progression. To address this issue we have performed an extensive RT-PCR analysis of VGCC expression in human melanocytes and a range of melanoma cell lines and biopsies. In addition, we have tested the functional expression of these channels using Ca(2+) imaging techniques and examined their relevance for the viability and proliferation of the melanoma cells. Our results show that control melanocytes and melanoma cells express channel isoforms belonging to the Ca(v) 1 and Ca(v) 2 gene families. Importantly, the expression of low voltage-activated Ca(v) 3 (T-type) channels is restricted to melanoma. We have confirmed the function of T-type channels as mediators of constitutive Ca(2+) influx in melanoma cells. Finally, pharmacological and gene silencing approaches demonstrate a role for T-type channels in melanoma viability and proliferation. These results encourage the analysis of T-type VGCCs as targets for therapeutic intervention in melanoma tumorigenesis and/or tumour progression. 相似文献
40.
In our recent publication, we describe the local anesthetic (LA) inhibition of the prokaryotic voltage gated sodium channel NaChBac. Despite the numerous functional and putative structural differences with the mammalian sodium channels, the data show that LA compounds effectively and reversibly inhibit NaChBac channels in a concentration range similar to resting blockade on eukaryotic Navs. In addition to current reduction, LA application accelerated channel inactivation kinetics of NaChBac which could be accounted for in a simple state-model whereby local anesthetics increase the probability of entering the inactivated state. We have further explored what state (or states) local anesthetic blockade of NaChBac could pertain to eukaryotic sodium channels, and what molecular similarities exist between these disparate channel families. Here we show that the rate of recovery from inactivation remains unaffected in the presence of local anesthetics. Further, we show that two sites that support use-dependent inhibition in eukaryotic channels, do not affect block to the same extent when mutated in NaChBac channels. The data indicate that the molecular determinants and the inherent mechanisms for LA block are likely to be divergent between bacterial and eukaryotic Navs, but future experiments will help define possible similarities. 相似文献