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排序方式: 共有2639条查询结果,搜索用时 15 毫秒
1.
Shaofeng Wang Jianwei Xu Yuejin Tong Lin Wang Chaobin He 《Polymer International》2005,54(9):1268-1274
A novel cholesterol‐imprinted polymer (CMIP‐H) was prepared by a hybrid method of covalent imprinting and non‐covalent imprinting. This approach involves the copolymerization of a template‐containing monomer, cholesteryl 2‐hydroxyethyl methacrylate carbonate, and a cross‐linker, followed by hydrolysis to afford a flexible guest‐binding site accompanied with the easy and efficient removal of a ‘sacrificial spacer’. The effect of solvent on the binding capacity of CMIP‐H towards cholesterol was studied, indicating that a good binding capacity towards cholesterol could be achieved in a less‐polar solvent. The binding experiments of CMIP‐H towards a series of structural analogues of cholesterol, including cholesterol acetate, progesterone and stigmasterol, were carried out in hexane. The results showed that CMIP‐H almost did not bind cholesterol acetate at all because the hydrogen‐bonding site is blocked. It exhibited a similar binding towards both cholesterol and stigmasterol, but much higher binding towards progesterone. Copyright © 2005 Society of Chemical Industry 相似文献
2.
摘要:本文对血管内皮细胞生长因子(VEGF)的结构、功能及生理作用,VEGFR的靶向抗肿瘤新生血管生成治疗,VEGF的PET示踪剂分类,采用18F标记的VEGFR酪氨酸激酶抑制剂类合成等几个方面做了简要叙述。 相似文献
3.
Amati Viviana; Werge Thomas M.; Cattaneo Antonino; Tramontane Anna 《Protein engineering, design & selection : PEDS》1995,8(4):403-408
Substance P G-protein coupled receptor and the antigen recognitionsite of a monoclonal antibody raised against substance P sharea stretch of five contiguous identical amino acids. This observationprompted us to build an atomic model of both the receptor andthe antibody and to analyse their common features. In particular,we report here that a pocket of similar size and compositionis present in both proteins, strongly suggesting a similarityin the mode of binding of both macromolecules to substance P.From the analysis of our models, the available data on the modeof binding of the antibody to substance P and recent data onsubstance P receptor mutants, we concluded that the pocket isvery likely to be involved in binding of the C-terminal 'messagesequence' of the tachykinin. This allowed us to suggest specificsite-directed mutants of the receptor which should shed somelight on the mechanism of peptide recognition by G-protein coupledreceptors. 相似文献
4.
The behavioral and electrophysiological activity of a mimic [(Z,E)7,9,11-dodecatrienyl formate] of the major sex pheromone component [(Z,E) 9,11,13-tetradecatrienal] of carob moth was assessed. Wind-tunnel bioassays demonstrated that the formate was as effective as natural gland extracts, and significantly more effective than the trienal alone or than the trienal blended with two minor pheromone components, in evoking source contact. Dispensers containing the formate were as effective as trienal-containing blend lures in attracting males when placed at the same dosage in traps in date gardens. Single-cell recordings showed that at least two olfactory neurons, differentiated by spike amplitude, are located in the long trichoid hairs on male carob moth antennae. Dose-response relationships indicated that puffs from cartridges loaded with at least 0.1 g of the formate or of the trienal were necessary to elicit spiking by either the small or the large-spiking cell within a sensillum. Cross-adaptation studies demonstrated that both compounds stimulated the same large-spiking cell. The frequencies of spikes evoked from the large cell when stimulated by emissions from 0.1-g, 1-g, or 10-g cartridges of either the formate or the trienal were not significantly different, suggesting that the formate is an effective mimic of the trienal at the antennal receptor cell level. 相似文献
5.
Lejla Medzikovic Hylja Heese Pieter B. van Loenen Cindy P. A. A. van Roomen Ingeborg B. Hooijkaas Vincent M. Christoffels Esther E. Creemers Carlie J. M. de Vries Vivian de Waard 《International journal of molecular sciences》2021,22(4)
Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis. 相似文献
6.
Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach. 相似文献
7.
Ann-Kathrin Eichelmann George C. Mayne Karen Chiam Steven L. Due Isabell Bastian Frederike Butz Tingting Wang Pamela J. Sykes Nicholas J. Clemons David S. Liu Michael Z. Michael Christos S. Karapetis Richard Hummel David I. Watson Damian J. Hussey 《International journal of molecular sciences》2021,22(11)
TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53. 相似文献
8.
The γ-aminobutyric acid type A receptor (GABAAR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GABAAR and dopamine D5 receptor (D5R) have been shown to physically interact in the hippocampus, but whether a functional cross-talk occurs is still debated. In the present study, we use a combination of imaging and single nanoparticle tracking in live hippocampal neurons to provide evidence that GABAARs and D5Rs form dynamic surface clusters. Disrupting the GABAAR–D5R interaction with a competing peptide leads to an increase in the diffusion coefficient and the explored area of both receptors, and a drop in immobile synaptic GABAARs. By means of patch-clamp recordings, we show that this fast lateral redistribution of surface GABAARs correlates with a robust depression in the evoked GABAergic currents. Strikingly, it also shifts in time the expression of long-term potentiation at glutamatergic synapses. Together, our data both set the plasma membrane as the primary stage of a functional interplay between GABAAR and D5R, and uncover a non-canonical role in regulating synaptic transmission. 相似文献
9.
Bilal Ahmad Maria Batool Moon-Suk Kim Sangdun Choi 《International journal of molecular sciences》2021,22(11)
Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics. 相似文献
10.
Excess lipid droplets are frequently observed in arterial endothelial cells at sites of advanced atherosclerotic plaques. Here, the role of tumor necrosis factor alpha (TNFα) in modulating the low-density lipoprotein (LDL) content in confluent primary human aortic endothelial cells (pHAECs) was investigated. TNFα promoted an up to 2 folds increase in cellular cholesterol, which was resistant to ACAT inhibition. The cholesterol increase was associated with increased 125I-LDL surface binding. Using the non-hydrolysable label, Dil, TNFα could induce a massive increase in Dil-LDL by over 200 folds. The elevated intracellular Dil-LDL was blocked with excess unlabeled LDL and PCSK9, but not oxidized LDL (oxLDL), or apolipoprotein (apoE) depletion. Moreover, the TNFα-induced increase of LDL-derived lipids was elevated through lysosome inhibition. Using specific LDLR antibody, the Dil-LDL accumulation was reduced by over 99%. The effects of TNFα included an LDLR cell surface increase of 138%, and very large increases in ICAM-1 total and surface proteins, respectively. In contrast, that of scavenger receptor B1 (SR-B1) was reduced. Additionally, LDLR antibody bound rapidly in TNFα-treated cells by about 30 folds, inducing a migrating shift in the LDLR protein. The effect of TNFα on Dil-LDL accumulation was inhibited by the antioxidant tetramethythiourea (TMTU) dose-dependently, but not by inhibitors against NF-κB, stress kinases, ASK1, JNK, p38, or apoptosis caspases. Grown on Transwell inserts, TNFα did not enhance apical to basolateral LDL cholesterol or Dil release. It is concluded that TNFα promotes LDLR functions through combined increase at the cell surface and SR-B1 downregulation. 相似文献