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1.
《Biomaterials》2015
The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a vulnerability factor and an attractive target for anticancer therapy. However, there is currently a lack of selective and effective platforms for the detection and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN) nanoplatform that is capable of detecting MTH1 mRNA and simultaneously suppressing MTH1 activity. The AuNP flares are made from AuNPs that are functionalized with a dense shell of MTH1 recognition sequences hybridized to short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces the opening of the pores and the release of S-crizotinib in an mRNA-dependent manner, leading to significant cytotoxicity in cancer cells and improved therapeutic response in mouse xenograft models. We anticipate that this nanoplatform may be an important step toward the development of MTH1-targeting theranostics and also be a useful tool for cancer phenotypic lethal anticancer therapy. 相似文献
2.
T B Vree Y A Hekster M W Tijhuis E F Termond J F Nouws 《Biopharmaceutics & drug disposition》1986,7(3):239-252
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes. 相似文献
3.
摘要:目的 探讨诱导分化剂苯乙酸(PA)对人结直肠癌细胞系HCT 8细胞周期及增殖的影响。 方法 应用MTT比色法,以1.0,2.0,3.0,4.0,5.0 mmol/L的PA作用于体外培养的HCT 8细胞,分别于24,48,72h后对细胞增殖进行检测;流式细胞术分析细胞周期。结果 随着PA浓度的增加(1~5 mmol/L)或药物作用时间的延长(24~72h),肿瘤细胞生长抑制率明显增加。PA1~5mmol/L作用24h细胞生长抑制率为5.1%-24.3%,48h为16.7%-72.3%,72h为30.2%-93.4%。PA作用细胞72h后,G0/G1期比例显著下降,S期比例相对升高,组间差异显著(P<0.05)。结论 PA在诱导分化结直肠癌HCT 8细胞过程中,可诱导G1细胞周期阻滞,抑制细胞增殖。 相似文献
4.
Harold T. Kyriazi George E. Carvell Joshua C. Brumberg Daniel J. Simons 《Brain research》1996,712(2):325
Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. lontophoretically-applied (−)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABAA and GABAB mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution. 相似文献
5.
维甲酸对涎腺腺样囊性癌实验性肺转移的抑制作用研究 总被引:1,自引:0,他引:1
本文利用已建立的涎腺腺样囊性癌肺转移动物模型,着重观察了Acc-M细胞株经维甲酸体外处理后其在裸鼠肺部形成转移能力的情况。结果表明:10μmol/L、20μmol/L两种浓度有明显抑制转移作用,转移率及肺转移灶重量、数目和直径均较对照组有显著下降(P〈0.05);但抑制作用无浓度依赖性,揭示维甲酸对Acc-M细胞株的作用位点是有限的。10μmol/L、20μmol/L可能是维甲酸抑制Acc-M细胞株转移的最低饱和浓度。 相似文献
6.
目的 研究乳酸杆菌属细菌对白色念珠菌的生长、菌落形成的影响。方法 使用多菌种混合培养技术,菌落形成单位培养技术。结果 在MRS培养基上混合培养显示:乳酸杆菌属中的嗜酸乳杆菌对白色念珠菌的生长抑制作用最强,从形态观察,被抑制生长后的白色念珠菌单细胞孢子的细胞壁和细胞质都有较大的改变,加入嗜酸乳杆菌后可将白色念珠菌的菌数由原来的(11.62±2.68)×10~3CFU/ml(每毫升菌落数)降低到(4.23±0.62)×10~3CFU/ml。两组比较有极显著性差异(P<0.01)。结论 嗜酸乳杆菌能抑制白色念珠菌的生长,破坏白色念珠菌细胞内正常结构。 相似文献
7.
注射用头孢曲松钠 (Ceftriaxoneforinjection)为长效、广谱的头孢菌素类抗生素 ,它对大多数革兰氏阴性杆菌具有高效的抗菌活性。目前无任何一种抗生素在对奇异变性杆菌的杀菌活性方面 ,可以和头孢曲松钠相比。 2 0 0 0版中国药典收载的方法为凝胶法 ,此法为限量检查法 ,不能准确测定样品中的内毒素含量 ,而定量法则可提供更灵敏而准确的内毒素检测方法。本文采用定量法 (动态比浊法 )来测定注射用头孢曲松钠的细菌内毒素含量。1 材料与仪器细菌内毒素检查用水Lot.No .0 0 1 2 2 70 ,规格5 0ml/Amp湛江安… 相似文献
8.
Jordi Llorens Cristina Su ol Josep M. Tusell Eduard Rodrí guez-Farr 《Neurotoxicology and teratology》1990,12(6):607-610
The inhibition of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to the GABAA receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC50 from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC50 values found in the literature. IC50 values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [35S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained. 相似文献
9.
用同位素标记~(15)Ca法测定大鼠突触体内游离钙的浓度,探讨了腺苷对高钾、N-甲基-D-天冬氨酸(NMDA)谷氨酸(Glu)等刺激所致的Ca~(2 )内流增加的影响。结果发现腺苷在10nmol/L~0.1μmol/L范围内对高钾、NMDA、Glu等刺激所致的Ca~(2 )内流有抑制作用,并呈剂量依赖关系,最大抑制率分别为41.68±7.68%、31.32±6.17%、37.52±2.29%。这可能是腺苷对缺血性脑损伤保护作用的机理。 相似文献
10.
A.M. Thierry C. Le Douarin J. Penit A. Perron J. Glowinski 《Brain research bulletin》1986,16(2):155-160
The stimulation of the ventro-medial mesencephalic tegmentum (VMT) induces an inhibition of the spontaneous activity of prefrontal cortical cells and blocks the excitatory responses evoked by the stimulation of the medio-dorsal nucleus of the thalamus (MD). This effect is mediated by the activation of the mesocortical dopaminergic (DA) system. In the present study, the influence of the systemic administration of several neuroleptics on the inhibition of prefrontal cortical cells induced by VMT stimulation has been analyzed in ketamine anaesthetised rats. The acute IP administration of fluphenazine (2 mg/kg), spiroperidol (2 mg/kg) or (+/-)sulpiride (100 mg/kg) reversed the inhibitory responses. Moreover, the number of cortical cells inhibited by VMT stimulation was considerably decreased after these treatments. Surprisingly, neither haloperidol at any dose used (0.1 to 0.5 mg/kg IV or 0.5 to 5 mg/kg IP) nor levomepromazine (25 mg/kg IP) nor the long acting neuroleptic, pipotiazine palmitic ester (32 mg/kg SC) blocked the inhibitory effect of VMT stimulation and in fact they lengthened the duration of the inhibition. Finally, the inhibition of MD evoked spikes in prefrontal cortical cells produced by VMT stimulation was no longer observed after sulpiride but persisted after haloperidol administration. Our findings confirm that the mesocortico-prefrontal DA neurons exert an inhibitory influence on target cells but they reveal differences in the efficacy of neuroleptics in blocking this effect. 相似文献