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111.
Trivedi CM Luo Y Yin Z Zhang M Zhu W Wang T Floss T Goettlicher M Noppinger PR Wurst W Ferrari VA Abrams CS Gruber PJ Epstein JA 《Nature medicine》2007,13(3):324-331
In the adult heart, a variety of stresses induce re-expression of a fetal gene program in association with myocyte hypertrophy and heart failure. Here we show that histone deacetylase-2 (Hdac2) regulates expression of many fetal cardiac isoforms. Hdac2 deficiency or chemical histone deacetylase (HDAC) inhibition prevented the re-expression of fetal genes and attenuated cardiac hypertrophy in hearts exposed to hypertrophic stimuli. Resistance to hypertrophy was associated with increased expression of the gene encoding inositol polyphosphate-5-phosphatase f (Inpp5f) resulting in constitutive activation of glycogen synthase kinase 3beta (Gsk3beta) via inactivation of thymoma viral proto-oncogene (Akt) and 3-phosphoinositide-dependent protein kinase-1 (Pdk1). In contrast, Hdac2 transgenic mice had augmented hypertrophy associated with inactivated Gsk3beta. Chemical inhibition of activated Gsk3beta allowed Hdac2-deficient adults to become sensitive to hypertrophic stimulation. These results suggest that Hdac2 is an important molecular target of HDAC inhibitors in the heart and that Hdac2 and Gsk3beta are components of a regulatory pathway providing an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure. 相似文献
112.
113.
Pei Lin Zheng-Fei Yan Chang-Tian Li MooChang Kook Tae-Hoo Yi 《Antonie van Leeuwenhoek》2018,111(10):1777-1784
A Gram-stain negative, aerobic, motile by flagella, rod-shaped strain (THG-T16T) was isolated from rhizosphere of Hibiscus syriacus. Growth occurred at 10–40 °C (optimum 28–30 °C), at pH 6.0–8.0 (optimum 7.0) and at 0–1.0% NaCl (optimum 0%). Based on 16S rRNA gene sequence analysis, the near phylogenetic neighbours of strain THG-T16T were identified as Nibribacter koreensis KACC 16450T (98.6%), Rufibacter roseus KCTC 42217T (94.7%), Rufibacter immobilis CCTCC AB 2013351T (94.5%) and Rufibacter tibetensis CCTCC AB 208084T (94.4%). The DNA G+C content of strain THG-T16T was determined to be 46.7 mol%. DNA–DNA hybridization values between strain THG-T16T and N. koreensis KACC 16450T, R. roseus KCTC 42217T, R. immobilis CCTCC AB 2013351T, R.tibetensis CCTCC AB 208084T were 33.5?±?0.5% (31.7?±?0.7% reciprocal analysis), 28.1?±?0.2% (25.2?±?0.2%), 17.1?±?0.9% (10.2?±?0.6%) and 8.1?±?0.3% (5.2?±?0.1%). The polar lipids were identified as phosphatidylethanolamine, two unidentified aminophospholipids, an unidentified aminolipid and three unidentified lipids. The quinone was identified as MK-7 and the polyamine as sym-homospermidine. The major fatty acids were identified as C16:1 ω5c, C17:1 ω6c, iso-C15:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) and summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B). On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics, and DNA–DNA hybridization data, strain THG-T16T represents a novel species of the genus Nibribacter, for which the name Nibribacter flagellatus sp. nov. is proposed. The type strain is THG-T16T(=?KACC 19188T?=?CCTCC AB 2016246T). 相似文献
114.
Yan-Yan Wang Fang-Zhou Xu Yun-Ying Zhu Baoan Song Dexia Luo Gang Yu Shunhong Chen Wei Xue Jian Wu 《Bioorganic & medicinal chemistry letters》2018,28(17):2979-2984
A series of pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety were synthesized, characterised, and evaluated for their activity against tobacco mosaic virus (TMV). Biological assays indicated that several of the derivatives exhibited significant activity against TMV. In particularly, compounds 5y and 5aa displayed excellent inactivating activity against TMV, with half maximal effective concentration (EC50) values of 70.3 and 53.65?μg/mL, respectively, which were much better than that of ribavirin (150.45?μg/mL), and 5aa was superior to ningnanmycin (EC50?=?55.35?μg/mL). Interactions of compounds 5y and 5aa with TMV coat protein (TMV-CP) were investigated using microscale thermophoresis and molecular docking. Compounds 5y and 5aa displayed strong binding capability to TMV-CP with dissociation constant (Kd) values of 22.6 and 9.8?μM, respectively. These findings indicate that pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base may be potential antiviral agents. 相似文献
115.
Artesunate exerts an anti‐immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression 下载免费PDF全文
116.
MicroRNAs (miRNAs) have recently emerged as regulators of metastasis. We provide insight into the behavior of miR-221 in colorectal cancer (CRC) metastasis by showing that miR-221 is significantly upregulated in metastatic CRC cell lines and tissues. miR-221 overexpression enhances, whereas miR-221 depletion reduces CRC cell migration and invasion in vitro and metastasis in vivo. We identify RECK as a direct target of miR-221, reveal its expression to be inversely correlated with miR-221 in CRC samples and show that its re-introduction reverses miR-221-induced CRC invasiveness. Collectively, miR-221 is an oncogenic miRNA which may regulate CRC migration and invasion through targeting RECK. 相似文献
117.
长时程增强诱导和维持过程中海马CA1区神经细胞粘附分子蛋白水平与mRNA表达的变化 总被引:2,自引:0,他引:2
既往研究发现,神经细胞粘附分子(neural cell adhesion molecules,NCAM)对海马CA1区突触传递长时程增强(longterm potentiation,LTP)的诱导和维持极为关键。本文采用原位杂交法和Western blot法,观察了大鼠海马腑片LTP诱导和维持过程中NCAM mRNA和蛋白水平的动态变化过程。结果显示,强直刺激诱发fEPSP斜率升高10 min时,海马CA1区NCAM mRNA染色阳性神经元数量显著增加(76.6±11.5个),NCAM蛋白水平亦明显升高(7.190±0.64任意单位/50μg蛋白)。强直刺激诱发fEPSP斜率升高1 h时,NCAM mRNA染色阳性神经元数量为73.3±14.0个,NCAM蛋白量为9.031±0.71任意单位/50 μg蛋白;与强直刺激后10 min比较,NCAM mRNA表达无显著变化,而NCAM蛋白水平变化明显。NMDA受体特异阻断剂AP-5在损害LTP的同时,显著抑制NCAM mRNA和蛋白的增加。实验结果表明,在大鼠海马LTP诱导和维持过程中,NCAM mRNA增强的表达相对稳定,而NCAM蛋白水平呈现先低后高的变化。 相似文献
118.
GRP78, a master regulator of the unfolded protein response (UPR) and cell signaling, is required for inner cell mass survival during early embryonic development. However, little is known about its role in adult hematopoietic stem cells (HSCs) and hematopoiesis. Here we generated a conditional knockout mouse model that acutely deletes Grp78 in the adult hematopoietic system. Acute GRP78 ablation resulted in a significant reduction of HSCs, common lymphoid and myeloid progenitors, and lymphoid cell populations in the mutant mice. The GRP78-null induced reduction of the HSC pool could be attributed to increased apoptosis. Chimeric mice with Grp78 deletion only in the hematopoietic cells also showed a loss of HSCs and lymphopenia, suggesting a cell intrinsic effect. Analysis of GRP78 deficient bone marrow (BM) cells showed constitutive activation of all the major UPR signaling pathways, including activation of eIF2α, ATF6, xbp-1 splicing, as well as caspase activation. A multiplex cytokine assay further revealed alteration in select cytokine and chemokine serum levels in the mutant mice. Collectively, these studies demonstrate that GRP78 plays a pleiotropic role in BM cells and contributes to HSC survival and the maintenance of the lymphoid lineage. 相似文献
119.
Pei Y Hancock PJ Zhang H Bartz R Cherrin C Innocent N Pomerantz CJ Seitzer J Koser ML Abrams MT Xu Y Kuklin NA Burke PA Sachs AB Sepp-Lorenzino L Barnett SF 《RNA (New York, N.Y.)》2010,16(12):2553-2563
Effective small interfering RNA (siRNA)-mediated therapeutics require the siRNA to be delivered into the cellular RNA-induced silencing complex (RISC). Quantitative information of this essential delivery step is currently inferred from the efficacy of gene silencing and siRNA uptake in the tissue. Here we report an approach to directly quantify siRNA in the RISC in rodents and monkey. This is achieved by specific immunoprecipitation of the RISC from tissue lysates and quantification of small RNAs in the immunoprecipitates by stem-loop PCR. The method, expected to be independent of delivery vehicle and target, is label-free, and the throughput is acceptable for preclinical animal studies. We characterized a lipid-formulated siRNA by integrating these approaches and obtained a quantitative perspective on siRNA tissue accumulation, RISC loading, and gene silencing. The described methodologies have utility for the study of silencing mechanism, the development of siRNA therapeutics, and clinical trial design. 相似文献
120.
Zenghong Ma Wei Cai Lei Wang Chenglin Du Weiwei Luo Linyu Niu Shuqing Xue Mengxin Ren Xinzheng Zhang Jingjun Xu 《Plasmonics (Norwell, Mass.)》2016,11(6):1481-1486
Magnetic hot spots, which implies confinements and enhancements of magnetic fields, are demonstrated in graphene junctions (GJs) in the mid-infrared range. The appearance of magnetic hot spots in GJs comes from the conduction currents in the junction. In further, the extinction resonance peaks suffer blue shift, along with the increases in the magnetic fields inside junction area, when the junction width reduces. In opposite to the circumstances for electric field enhancements, neither magnetic field enhancements nor resonance frequency of GJs is perturbed by the intrinsic nonlocal electronic response of graphene. Such nonlocality immunized magnetic enhancement could be explained by the polarization dependent property of nonlocal effect. 相似文献