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排序方式: 共有1682条查询结果,搜索用时 15 毫秒
1.
Deniz Caylioglu Rieke Johanna Meyer Dana Hellmold Carolin Kubelt Michael Synowitz Janka Held-Feindt 《International journal of molecular sciences》2021,22(7)
Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences. 相似文献
2.
Lissy Z. F. Gross Mariana Sacerdoti Prof. Albrecht Piiper Prof. Stefan Zeuzem Dr. Alejandro E. Leroux Dr. Ricardo M. Biondi 《ChemMedChem》2020,15(18):1682-1690
Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein. 相似文献
3.
Kazuo Tsubota Stephen C. Pflugfelder Zuguo Liu Christophe Baudouin Hyo Myung Kim Elisabeth M. Messmer Friedrich Kruse Lingyi Liang Jimena Tatiana Carreno-Galeano Maurizio Rolando Norihiko Yokoi Shigeru Kinoshita Reza Dana 《International journal of molecular sciences》2020,21(23)
Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint. 相似文献
4.
María Clara Verdi Constanza Melian Patricia Castellano Graciela Vignolo Mariana Blanco Massani 《International Journal of Food Science & Technology》2020,55(1):267-275
The effectiveness of antimicrobial mixtures against Listeria innocua 7, used as a L. monocytogenes surrogate, was investigated in broth and a food system. Synergistic effects were found for nisin (Nis), potassium sorbate (PS), calcium propionate (CP) and sodium lactate (SL), Nis + PS being the most effective binary mixture that exhibited listericidal activity in broth. To assess the effect of adding lactocin AL705 (AL705) to Nis + organic acid salt combinations, tridimensional isobolograms were generated. Sub-MIC combinations of the antimicrobials exerted bactericidal activity against L. innocua 7 after AL705 addition to the binary mixtures. However, when applied on Sardo cheese contaminated with L. innocua 7 (initial inoculum 4.45 ± 0.06 CFU g−1), only Nis + PS + AL705 produced count reductions respect to the control, reaching 3.04 ± 0.35 CFU g−1 counts after 15 days at 15 °C. Ternary combinations containing AL705 showed potential to reduce antimicrobial usages for L. innocua 7 inhibition. 相似文献
5.
6.
Mostofa Shamim Somnath Sinhamahapatra Jahangir Hossain Sayan Lahiri Kausik Dana 《Ceramics International》2018,44(2):1868-1874
The mechanistic pathway of MgO-Al2O3 reaction in solid state to form MgAl2O4 spinel was investigated to correlate the kinetic parameters with ratio of reactants (MgO:Al2O3) and with the presence of a doping agent, TiO2. The time-temperature-expansion data of oxide compacts was analyzed using several model free analyses and model based (linear and non-linear) kinetic algorithms. These indicated that spinel formation process can be best described by single step with n-dimensional Avrami equation for every MgO:Al2O3 ratio, irrespective of titania dopant. The activation energy (Ea) of the process was proportional to % spinel formed in each system and validated with quantitative XRD analysis. The higher value of Avrami coefficient (n) in 90 wt% Al2O3 compositions has been explained with geometric considerations of powder packing. Incorporations of 1% TiO2 in the MgO: Al2O3 oxide compact did not markedly affect the reaction model, frequency factor and Activation energy. 相似文献
7.
Gotlib Ian H.; Krasnoperova Elena; Yue Dana Neubauer; Joormann Jutta 《Canadian Metallurgical Quarterly》2004,113(1):127
An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1,000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1,000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
Learning to Perceive and Act by Trial and Error 总被引:5,自引:1,他引:4
This article considers adaptive control architectures that integrate active sensory-motor systems with decision systems based on reinforcement learning. One unavoidable consequence of active perception is that the agent's internal representation often confounds external world states. We call this phoenomenon perceptual aliasingand show that it destabilizes existing reinforcement learning algorithms with respect to the optimal decision policy. We then describe a new decision system that overcomes these difficulties for a restricted class of decision problems. The system incorporates a perceptual subcycle within the overall decision cycle and uses a modified learning algorithm to suppress the effects of perceptual aliasing. The result is a control architecture that learns not only how to solve a task but also where to focus its visual attention in order to collect necessary sensory information. 相似文献
9.
Mariana Ušáková Jozef Lukáč Rastislav Dosoudil Vladimír Jančárik Anna Grusková Elemír Ušák Jozef Sláma Jan Šubrt 《Journal of Materials Science: Materials in Electronics》2007,18(12):1183-1189
The paper is devoted to the preparation of NiZn ferrite with small substitutions of copper by means of ceramic technology.
The influence of small Cu substitution on the microstructural and magnetic properties of NiZn ferrites have been analysed
by means of various experimental methods and interpreted from the point of view of preparation technology optimisation and
possible applications of such materials. A strong correlation between the substituent content and resulting properties has
been observed, thus allowing preparation of material with the properties tailored for any particular application. 相似文献
10.
Subhalf micron (0.2 nm) space and amplitude linear periodic structures and an array of dot images are obtained with the Nd:YAG laser irradiation on Kapton polyimide films, poly(ethylene terephthalate) films, spin-coated polyimide films and others. Different from the excimer laser irradiation, which requires a polarizer, our solid state Nd:YAG laser source provides polarized beams without a polarizer with advantage over excimer laser irradiation. AFM and SEM studies have been carried out. XPS studies of laser exposed areas indicate no significant chemical reactions took place on exposed areas. 相似文献