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961.
Andrea Cippitelli Jinhua Wu Kelly A Gaiolini Daniela Mercatelli Jennifer Schoch Michelle Gorman Alejandra Ramirez Roberto Ciccocioppo Taline V Khroyan Dennis Yasuda Nurulain T Zaveri Conrado Pascual Xinmin Xie Lawrence Toll 《British journal of pharmacology》2015,172(7):1834-1845
Background and Purpose
The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT-1001 has been recently described as a high-affinity and selective α3β4 nAChR antagonist that blocks nicotine self-administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine-suppressive effects of AT-1001.Experimental Approach
Effects of AT-1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.Key Results
AT-1001 and its analogue AT-1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT-1001 and varenicline also had very different in vivo properties. Firstly, AT-1001 did not exhibit reinforcing properties per se while varenicline was self-administered. Secondly, systemic treatment with AT-1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT-1001 selectively blocked nicotine self-administration without altering alcohol lever pressing as assessed in an operant co-administration paradigm.Conclusions and Implications
These findings describe a more complex AT-1001 in vitro profile than previously appreciated and provide further support for the potential of AT-1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications. 相似文献962.
Nanxin Li Yanni Hao Jipan Xie Peggy L. Lin Zhou Zhou Yichen Zhong 《Current medical research and opinion》2015,31(8):1573-1582
963.
Molecular mechanisms of human thyrocyte dysfunction induced by low concentrations of polychlorinated biphenyl 118 through the Akt/FoxO3a/NIS pathway
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Hongwei Guo Hui Yang Huanhuan Chen Wen Li Jinmei Tang Pei Cheng Yuchun Xie Yun Liu Guoxian Ding Dai Cui Xuqin Zheng Yu Duan 《Journal of applied toxicology : JAT》2015,35(9):992-998
Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that can interfere with multiple organ systems of humans. Previously, we concluded that persistent exposure to low doses of PCB118 could severely damage the thyroidal structure, dramatically decrease the concentration of serum thyroid hormones and inhibit the pivotal gene expressions such as sodium/iodide symporter (NIS) and thyroglobulin (Tg). To explore the molecular mechanisms of thyrocyte dysfunction induced by 2,3′,4,4′,5‐pentachlorobiphenyl (PCB118), monolayer cultured human thyroid epithelial cells (HTECs) were treated with PCB118 or dimethyl sulfoxide (DMSO) as a control. Our results indicated that relatively higher concentrations of PCB118 could induce a loss in the viability of HTEC. In cultures with concentrations of PCB118 from 0.025 to 25 nM, which did not affect cell viability or apoptosis, concentrations of Tg and thyroxine (T4) were significantly decreased compared with those in the controls. In addition, mRNA and protein levels of Akt were increased significantly in the PCB118‐treated groups, whereas FoxO3a expression did not show particular variation. Furthermore, exposure to PCB118 was associated with a significant increase of the protein levels of p‐Akt and p‐FoxO3a, and these effects were blocked by LY294002. In contrast, mRNA and protein expression levels of NIS were decreased significantly, and this effect was blocked by LY294002. Unlike control cells, a cytoplasmic shift of FoxO3a was observed in the PCB118‐treated group. Our research suggests that PCB118 may induce thyrocyte dysfunction through the Akt/FoxO3a/NIS signalling pathway, which provides potential new insights for finding interventions to counteract the damage to the human body caused by PCBs. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
964.
Simulated microgravity promotes monocyte adhesion to rat aortic endothelium via nuclear factor‐κB activation
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965.
966.
Jing Guo Ying Xie Qiao-Lei Wu Wen-Tian Zeng Albert S. C. Chan Jiang Weng Gui Lu 《RSC advances》2018,8(29):16202
An aerobic decarboxylative cross-coupling of α-amino acids with diverse C–H nucleophiles has been realized using Cu2(OH)2CO3 (1 mol%) as the catalyst under air. This protocol enables highly efficient formation of various C(sp3)–C(sp3), C(sp3)–C(sp2) and C(sp3)–C(sp) bonds under simple conditions without the use of any ligand or extra oxidant, providing a practical approach to numerous nitrogen-containing compounds in good to excellent yields. The efficiency and practicability were also demonstrated by the gram-scale experiment and three-step synthesis of a Rad51 inhibitor.An aerobic decarboxylative cross-coupling of α-amino acids was realized using 1 mol% Cu2(OH)2CO3 catalyst under ligand free conditions. 相似文献
967.
Liang Hu Xie Peng Linlin Qin Ru Wang Zhengfeng Fang Yan Lin Shengyu Xu Bin Feng De Wu Lianqiang Che 《RSC advances》2018,8(29):16152
The aim of the present study was to investigate the effect of dietary nucleotides supplementation on the antioxidant status of piglets affected by intrauterine growth retardation (IUGR). Fourteen pairs of normal birth weight (NBW) and IUGR piglets were fed either a control diet (CON) or a nucleotides supplementation diet (NT) from 7 d of age to 28 d postnatal. Blood, liver and jejunum samples were collected at the end of the study. The results showed that IUGR piglets had decreased (P < 0.05) concentrations of plasma total antioxidant capability (T-AOC) and total superoxide dismutase (T-SOD), gene expressions of hepatic cytoplasmic copper/zinc SOD (CuZnSOD) and PPARγ coactivator-1α (PGC-1α) and jejunal glutathione peroxidase (GPX) and extracellular superoxide dismutase (ESOD), accordingly, there was markedly higher (P < 0.05) plasma malondialdehyde (MDA) and hepatic and jejunal mitochondria DNA content in the IUGR piglets relative to NBW piglets. Regardless of body weight, dietary NT supplementation significantly increased (P < 0.05) plasma concentrations of T-AOC, T-SOD, CuZnSOD, GPX and the ratio of reduced glutathione to oxidized glutathione, hepatic T-SOD, GPX and mitochondria DNA content, while hepatic MDA concentration was markedly decreased (P < 0.05) 19.1% by NT diet. Furthermore, the gene expressions of hepatic glutathione reductase, CuZnSOD, nuclear erythroid 2-related factor 2, PGC-1α and nuclear respiratory factor-1 (NRF-1) and jejunal GPX, CuZnSOD, ESOD and NRF-1 were significantly increased (P < 0.05) by NT diet, whereas the gene expression of Kelch-like ECH-associated protein 1 were markedly decreased (P < 0.05) compared with that of piglets fed with CON diet. These results indicate that dietary NT supplementation prevents the effect of IUGR on oxidative status and mitochondria DNA damage through improving the non-enzymatic and enzymatic antioxidant capacities as well as mitochondria biogenesis of piglets.The aim of the present study was to investigate the effect of dietary nucleotides supplementation on the antioxidant status of piglets affected by intrauterine growth retardation (IUGR). 相似文献
968.
Shuai Zhao Shicheng Xie Peipei Sun Zheng Zhao Lin Li Xiaoming Shao Xiaolin Liu Zhenxiang Xin 《RSC advances》2018,8(32):17813
A novel graphene–silicon dioxide hybrid (HGS) was prepared by plant polyphenol-tannic acid (TA) functionalized pristine graphene (G-TA) and primary amine-containing silane coupling agent modified SiO2 (Si–NH2). Through strong hydrogen-bonding interaction between the phenolic hydroxyl groups on G-TA and primary amine groups on Si–NH2, SiO2 was uniformly loaded to the surface of graphene. Due to the synergistic dispersion effect of graphene and SiO2, which prevents restacking and re-aggregating of both graphene and SiO2, HGS hybrids were distributed evenly in the natural rubber (NR) matrix (HGS@NR). Simultaneously, the surface roughness of graphene after loading SiO2 and the interfacial interaction between the HGS hybrid and NR matrix were substantially improved. Due to the good dispersion and strong interface, the overall properties of HGS@NR nanocomposites are drastically enhanced compared with those of GS@NR nanocomposites prepared by dispersing the blend of unmodified graphene and SiO2 (GS) in NR. The HGS@NR nanocomposites possess the highest tensile strength up to 27.8 MPa at 0.5 wt% and tear strength of 60.2 MPa at 0.5 wt%. Thermal conductivities of the HGS@NR nanocomposites were found to be 1.5-fold better than that of the GS@NR nanocomposites. Also, the HGS@NR nanocomposites exhibit excellent abrasive resistant capacity that is nearly 2-fold better than that of the GS@NR nanocomposites. These results suggest that HGS has great potential in high-performance nanocomposites and a new strategy of constructing the efficient graphene–SiO2 hybrid fillers has been established.A novel graphene–silicon dioxide hybrid (HGS) was prepared by plant polyphenol-tannic acid (TA) functionalized pristine graphene (G-TA) and primary amine-containing silane coupling agent modified SiO2 (Si–NH2). 相似文献
969.
Leyu Wang Tao Yu Zongliang Xie Eethamukkala Ubba Tianya Zhan Zhiyong Yang Yi Zhang Zhenguo Chi 《RSC advances》2018,8(33):18613
A couple of gated photochromic molecules TrPEP and TrPEPO with AIEgen have been rationally designed and synthesized. No photochromism is detected for TrPEP whilst TrPEPO shows obvious photochromic properties in the solution state. By adding equimolar H2O2 aqueous solution to the TrPEP solution, the photochromic properties would be quickly turned on. The oxidation reagent acts as a gate to switch the photochromic properties by switching the triphenylphosphine group to a triphenylphosphine oxide group. Both TrPE and TrPEO display typical AIE phenomena. Different intensive emission bands with the emission maxima of 500 nm and 455 nm are detected before (TrPEP) and after (TrPEPO) oxidization in solid states. Combining the AIEgens, photochromic ON/OFF states can be easily indicated by the different emission colors in the solid state. Single crystal analyses and TD-DFT calculations were carried out to further investigate the photophysical and photochromic properties of these compounds. These new triphenylethylene derivatives provide a new strategy to achieve gated photochromic materials with simple chemical structures and gate indicators.Gated photochromic molecule: switchable photochromic materials with AIEgen were achieved. Oxidation reagents act as gates to switch the photochromic properties. 相似文献