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排序方式: 共有1968条查询结果,搜索用时 156 毫秒
81.
目的:探讨地高辛片对老年慢性心力衰竭患者血清血清糖类抗原(CA125)、心钠肽(ANP)、脑钠肽(BNP)、基质金属蛋白酶9(MMP-9)及金属蛋白酶组织抑制剂(TIMP-1)水平的影响。方法:收集我院老年慢性心力衰竭患者100例,随机分为对照组和实验组,每组各50例,对照组患者给予常规治疗,实验组患者在对照组的基础上给予地高辛片。比较治疗前后两组患者血清糖类抗原(CA125)、心钠肽(ANP)、脑钠肽(BNP)、基质金属蛋白酶9(MMP-9)及金属蛋白酶组织抑制剂(TIMP-1)水平。结果:与治疗前相比,两组患者血清CA125、ANP、BNP及MMP-9水平降低,TIMP-1水平升高(P0.05);治疗后与对照组相比,实验组CA125水平(34.05±4.63)较低,ANP水平较低(216.98±27.65),BNP水平较低(437.62±45.26),MMP-9水平较低(550.17±65.15),TIMP-1水平较高(182.32±21.78)(P0.05)。结论:地高辛片能够改善老年慢性心力衰竭患者心肌功能,推测其机制可能与降低血清CA125、ANP、BNP、MMP-9水平,升高TIMP-1水平有关。 相似文献
82.
Conveying Advanced Li‐ion Battery Materials into Practice The Impact of Electrode Slurry Preparation Skills 下载免费PDF全文
Li‐ion batteries (LIB's) are of the greatest practical utility for portable electronics and electric vehicles (EV's). LIB energy, power and cycle life performances depend on cathode and anode compositions and morphology, electrolyte composition and the overall cell design. Electrode morphology is influenced by the shape and size of the active material (AM), conductive additive (CA) particles, the polymeric binder properties, and also on the AM/CA/binder mass ratio. At the same time, it also substantially depends on the electrode preparation process. This process is usually comprised of mixing a solvent, a binder, AM and CA powders, and casting the resulting slurry onto a current collector foil followed by a drying process. Whereas the problems of electrode morphology and their influence on the LIB‐electrode performance always receive a proper attention, the influence of slurry properties and slurry preparation techniques on the electrode morphology is often overlooked or at least underrated. The present work summarizes the current state‐of‐the‐art in the field of LIB‐electrode precursor slurries preparation, characterized by multicomponent compounds and large variations in sizes and shapes of the solid components. Approaches to LIB‐electrode slurry preparation are outlined and discussed in the context of the ultimate LIB‐electrode morphology and performance. 相似文献
83.
84.
Fuyang Li Gwanghyun Gwon Aera Jo Ae‐Kyoung Kim Taeyoon Kim Ok‐kyu Song Sang Eun Lee Yunje Cho 《The EMBO journal》2016,35(7):743-758
ATP‐dependent DNA end recognition and nucleolytic processing are central functions of the Mre11/Rad50 (MR) complex in DNA double‐strand break repair. However, it is still unclear how ATP binding and hydrolysis primes the MR function and regulates repair pathway choice in cells. Here, Methanococcus jannaschii MR‐ATPγS‐DNA structure reveals that the partly deformed DNA runs symmetrically across central groove between two ATPγS‐bound Rad50 nucleotide‐binding domains. Duplex DNA cannot access the Mre11 active site in the ATP‐free full‐length MR complex. ATP hydrolysis drives rotation of the nucleotide‐binding domain and induces the DNA melting so that the substrate DNA can access Mre11. Our findings suggest that the ATP hydrolysis‐driven conformational changes in both DNA and the MR complex coordinate the melting and endonuclease activity. 相似文献
85.
The Tau/A152T mutation,a risk factor for frontotemporal‐spectrum disorders,leads to NR2B receptor‐mediated excitotoxicity 下载免费PDF全文
Astrid Sydow Frank JA Dennissen Zuzana Siskova Eckhard Mandelkow Eva‐Maria Mandelkow 《EMBO reports》2016,17(4):552-569
We report on a novel transgenic mouse model expressing human full‐length Tau with the Tau mutation A152T (hTauAT), a risk factor for FTD‐spectrum disorders including PSP and CBD. Brain neurons reveal pathological Tau conformation, hyperphosphorylation, mis‐sorting, aggregation, neuronal degeneration, and progressive loss, most prominently in area CA3 of the hippocampus. The mossy fiber pathway shows enhanced basal synaptic transmission without changes in short‐ or long‐term plasticity. In organotypic hippocampal slices, extracellular glutamate increases early above control levels, followed by a rise in neurotoxicity. These changes are normalized by inhibiting neurotransmitter release or by blocking voltage‐gated sodium channels. CA3 neurons show elevated intracellular calcium during rest and after activity induction which is sensitive to NR2B antagonizing drugs, demonstrating a pivotal role of extrasynaptic NMDA receptors. Slices show pronounced epileptiform activity and axonal sprouting of mossy fibers. Excitotoxic neuronal death is ameliorated by ceftriaxone, which stimulates astrocytic glutamate uptake via the transporter EAAT2/GLT1. In summary, hTauAT causes excitotoxicity mediated by NR2B‐containing NMDA receptors due to enhanced extracellular glutamate. 相似文献
86.
Ramin Ekhteiari Salmas Mert Mestanoglu Elif Çelenk Kaya 《Journal of enzyme inhibition and medicinal chemistry》2016,31(1):31-37
A series of hydroxy and phenolic compounds have been assayed for the inhibition of two physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic human isozymes I and II. The investigated molecules showed inhibition constants in the range of 1.07–4003 and 0.09–31.5?μM at the hCA I and hCA II enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are compared using three different scoring algorithms, namely Glide/SP, Glide/XP and Glide/IFD. In addition, different ADME (absorption, distribution, metabolism and excretion) analysis was performed. All the examined compounds were found within the acceptable range of pharmacokinetic profiles. 相似文献
87.
Ramin Ekhteiari Salmas Murat Senturk Mine Yurtsever 《Journal of enzyme inhibition and medicinal chemistry》2016,31(3):425-433
Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for adjusting the pH imbalance in tumor cells. In the present work, we represented the successful application of high throughput virtual screening (HTVS) of large dataset from ZINC database included of ~7 million compounds to discover novel inhibitors of CA IX. HTVS and molecular docking were performed using consequence Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD) molecular docking protocols. For each compound, docking code calculates a set of low-energy poses and then exhaustively scans the binding pocket of the target with small compounds. Novel CA IX inhibitor candidates were suggested based on molecular modeling studies and a few of them were tested using in vitro analysis. These compounds were determined as good inhibitors against human CA IX target with Ki in the range of 0.85–1.58?μM. In order to predict the pharmaceutical properties of the selected compounds, ADME (absorption, distribution, metabolism and excretion) analysis was also carried out. 相似文献
88.
《Bioorganic & medicinal chemistry》2016,24(16):3643-3648
Herein we report an in vitro kinetic evaluation against the most relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms (I, II, IX and XII) of a small series of lactate dehydrogenase (LDH, EC 1.1.1.27) inhibitors. All compounds contain a primary sulfonamide zinc-binding group (ZBG) substituted with the 2-thio-6-oxo-1,6-dihydropyrimidine scaffold. By means of X-ray crystallographic experiments we explored the ligand–enzyme binding modes, thus highlighting the contribution of the 2-thio-6-oxo-1,6-dihydropyrimidine moiety to the stabilization of the complex. 相似文献
89.
目的:探讨胃癌根治术后腹腔灌注化疗对患者血清CEA(血清癌胚抗原,carcinoembryonic antigen)、CA19-9(糖链抗原19-9,carbohydrate antigen19-9)水平及免疫功能的影响。方法:回顾性2015年2月至2017年4月我院收治的胃癌患者临床资料,依据接受治疗方案不同分为全身静脉化疗组(对照组)和全身静脉化疗联合腹腔热灌注化疗组(观察组),每组各41例。检测和比较两组患者化疗前(治疗前)与化疗1个月后(治疗后)血清肿瘤标志物CEA、CA19-9与免疫功能指标水平的变化,治疗后毒副作用发生情况及治疗前后生活质量的改善情况。结果:治疗前,两组间血清CEA、CA19-9、CD3~+、CD4~+、CD8~+、CD4+/CD8~+水平比较差异均无统计学意义(P0.05);观察组治疗后血清CEA、CA19-9及CD8~+水平显著低于对照组,CD3~+、CD4~+、CD4~+/CD8~+水平显著高于对照组,差异有统计学意义(P0.05);两组骨髓抑制、恶心呕吐、腹痛腹泻及肠梗发生率比较差异均不显著无统计学意义(P=0.478,0.668,0.315,0.552);观察组生活质量改善总有效率为85.37%,显著高于对照组(70.73%,P=0.017)。结论:与单纯全身化疗相比,胃癌根治术后腹腔灌注化疗可更有效降低患者血清CEA、CA19-9水平,改善患者免疫功能,提高其生活质量,且安全性较高。 相似文献
90.
Daniel Pereda Ibrahim Al‐Osta Albert E. Okorocha Alexander Easton Nicholas A. Hartell 《Aging cell》2019,18(5)
The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long‐term potentiation requires stronger stimulation for induction in aged rats and mice and long‐term depression becomes more prevalent. An age‐dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age‐dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T‐maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired‐pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age‐dependent change in the properties or numbers of presynaptic calcium channels. 相似文献