• 【XLerk的鉴定,Eph家族配体在非洲爪蟾的中胚层诱导和神经发生过程中受到调节。】 复制标题 收藏 收藏
    DOI:10.1038/sj.onc.1201082 复制DOI
    作者列表:Jones TL,Karavanova I,Chong L,Zhou RP,Daar IO
    BACKGROUND & AIMS: We have isolated and characterized the first Xenopus transmembrane Eph ligand, XLerk (Xenopus Ligand for Eph Receptor Tyrosine Kinases). While this ligand has 72% identity with the closest mammalian family member, Lerk-2, it is the cytoplasmic domain of this molecule that is the most conserved domain with 95% identity. XLerk exists as a maternally expressed mRNA, however, expression of transcripts and protein increase during gastrulation and again in the late swimming tadpole stage. In the adult, XLerk is expressed at low levels in most adult tissues with increased levels observed in the kidney, oocytes, ovary and testis. While low levels of XLerk expression are observed in the adult brain, in situ hybridization analysis demonstrates prominent expression in the developing olfactory system, retina, hindbrain, cranial ganglia, and somites. Furthermore, we have shown that XLerk transcripts are significantly elevated during mesoderm induction caused by activin and FGF, but not during noggin-induced neuralization. These results suggest a role for XLerk in the developing mesenchymal and nervous tissue.

    背景与目标: 我们已经分离并表征了第一个非洲爪蟾跨膜Eph配体XLerk (用于Eph受体酪氨酸激酶的非洲爪蟾配体)。虽然该配体与最接近的哺乳动物家族成员Lerk-2具有72% 的同一性,但该分子的细胞质结构域是具有95% 同一性的最保守的结构域。XLerk作为母体表达的mRNA存在,但是,转录本和蛋白质的表达在胃形成过程中以及在游泳tar后期再次增加。在成人中,XLerk在大多数成人组织中以低水平表达,在肾脏,卵母细胞,卵巢和睾丸中观察到水平升高。虽然在成人大脑中观察到低水平的XLerk表达,但原位杂交分析表明,在发育中的嗅觉系统,视网膜,后脑,颅神经节和体节中表达显着。此外,我们已经表明,在由激活素和FGF引起的中胚层诱导过程中,XLerk转录本显着升高,但在noggin诱导的神经化过程中却没有。这些结果表明XLerk在发育中的间充质和神经组织中起作用。
  • 【凝血酶刺激的血小板结合诱导白细胞中细胞因子表达。】 复制标题 收藏 收藏
    DOI:10.1161/01.cir.95.10.2387 复制DOI
    作者列表:Neumann FJ,Marx N,Gawaz M,Brand K,Ott I,Rokitta C,Sticherling C,Meinl C,May A,Schömig A
    BACKGROUND & AIMS: BACKGROUND:Activated platelets tether and activate myeloid leukocytes. To investigate the potential relevance of this mechanism in acute myocardial infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI.

    METHODS AND RESULTS:We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty (PTCA) and in 20 patients undergoing elective PTCA. Throughout the study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients (mean +/- SE of fluorescence [channels] before PTCA: 77 +/- 16 versus 35 +/- 9; P = .003). In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for interleukin (IL),1 beta, IL-8, and monocyte chemoattractant protein (MCP)-1 in unfractionated leukocytes. After 4 hours, IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36% and 210 +/- 7%, respectively, and cellular MCP-1 content had increased by 170 +/- 8%. Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation. Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production.

    CONCLUSIONS:In patients with AMI, leukocyte-platelet adhesion is increased. Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes. Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.

    背景与目标: 背景 : 激活的血小板束缚并激活髓样白细胞。为了研究该机制在急性心肌梗死 (AMI) 中的潜在相关性,我们检查了白细胞-血小板粘附引起的细胞因子诱导以及AMI患者白细胞-血小板缀合物的发生。
    方法和结果 : 我们在直接经皮腔内冠状动脉成形术 (PTCA) 之前和之后5天每天获得20例AMI患者的外周静脉血样本,并在20例接受选择性PTCA的患者中获得外周静脉血样本。在整个研究期间,白细胞的CD41免疫荧光 (流式细胞术) 显示AMI患者与对照组患者相比白细胞-血小板粘附增加 (PTCA前荧光 [通道] 的平均值 +/- SE: 77 +/- 16对35 +/- 9; P = .003)。在体外,凝血酶刺激的固定血小板与中性粒细胞和单核细胞结合。在2小时内,这导致未分级白细胞中白介素 (IL),1β,IL-8和单核细胞趋化蛋白 (MCP)-1的mRNA增加。4小时后,无细胞上清液的IL-1 β 和IL-8浓度分别增加268 +/- 36% 和210 +/- 7%,细胞MCP-1含量增加170 +/- 8%。将活化的血小板添加到粘附的单核细胞中具有相似的作用,并且与核因子-κ B活化有关。抗P选择素抗体的结合抑制作用降低了活化血小板对细胞因子产生的作用。
    结论 : 在AMI患者中,白细胞-血小板粘附增加。活化血小板的结合诱导白细胞中的IL-1 β 、IL-8和MCP-1。我们的发现表明,白细胞-血小板粘附有助于调节AMI的炎症反应。
  • 【恶臭假单胞菌U对D-葡萄糖的分解代谢是通过细胞外转化为D-葡萄糖酸并诱导特定的葡萄糖酸转运系统而发生的。】 复制标题 收藏 收藏
    DOI:10.1099/00221287-143-5-1595 复制DOI
    作者列表:Schleissner C,Reglero A,Luengo JM
    BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

    背景与目标: 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖,但需要 (i) 通过位于外周的组成型葡萄糖脱氢酶将其氧化为D-葡萄糖酸 (对渗透休克不敏感),(ii) D-葡萄糖酸在细胞外培养基中的积累,(iii) 诱导负责吸收D-葡萄糖酸的特定能量依赖性转运系统。该吸收系统在50 mM磷酸钾缓冲液 (pH 7.0) 中显示了在30 ℃ 下的最大转运速率。在这些条件下,计算的D-葡萄糖酸的K(m) 为6.7微米。此外,还确定了特定于葡萄糖摄取的不同转运系统。它具有活性,并在50 mM磷酸钾缓冲液 (pH 6.0) 中的35摄氏度下显示出最大的吸收速率,K(m) 值为8.3微米。
  • 【4 '-O-甲基化类黄酮在B16F10黑色素瘤细胞中诱导黑素生成。】 复制标题 收藏 收藏
    DOI:10.1007/s11418-012-0727-y 复制DOI
    作者列表:Horibe I,Satoh Y,Shiota Y,Kumagai A,Horike N,Takemori H,Uesato S,Sugie S,Obata K,Kawahara H,Nagaoka Y
    BACKGROUND & AIMS: :Agents to control melanogenesis are in demand for the development of cosmetics to improve pigmentation disorders of skin and hair. In this study, we examined and evaluated the effects of flavonoids on melanogenesis in the melanogenic cells model, murine B16F10 melanoma cells. In the course of this study, we found that incubation of the cells in a medium containing 10 μM of the 4'-O-methylated flavonoids, diosmetin (4'-O-methylluteolin), acacetin (4'-O-methylapigenin) or kaempferide (4'-O-methylkaempferol), increased the melanin contents of the cells 3- to 7-fold higher than the control cells. The concentration-dependence test revealed that 20 μM acacetin showed the highest effect, up to 33-fold higher than the vehicle. On the other hand, the corresponding 4'-OH-type flavonoids, luteolin, apigenin and kaempferol, had a significantly smaller effect. Furthermore, by evaluating the melanogenic proteins, we found that the cells treated with 4'-O-methylated flavonoids showed higher tyrosinase activity, as well as upregulation of tyrosinase expression, preceded by activation of cAMP response element binding protein (CREB) and extracellular signal-regulated kinases types 1 and 2 (ERK1/2). These results indicate that the 4'-O-methyl group of flavonoids plays an important role in the induction of melanogenesis by activating its major signal transduction pathway through the upregulation of phospho-CREB in murine B16F10 melanoma cells.
    背景与目标: : 控制黑素生成的药物是化妆品开发的需求,以改善皮肤和头发的色素沉着疾病。在这项研究中,我们检查并评估了类黄酮对黑色素生成细胞模型鼠B16F10黑素瘤细胞中黑色素生成的影响。在这项研究的过程中,我们发现细胞在含有10μm的4 '-O-甲基化类黄酮,地奥美汀 (4'-O-methylluteolin),acacetin (4 '-O-methyapigenin) 或kaempferide (4'-O-methylameferol),使细胞的黑色素含量比对照细胞高3至7倍。浓度依赖性测试表明,20μm acacetin的效果最高,比媒介物高33倍。另一方面,相应的4 '-OH型类黄酮木犀草素,芹菜素和山奈酚的作用明显较小。此外,通过评估黑素蛋白,我们发现用4 '-O-甲基化类黄酮处理的细胞显示出更高的酪氨酸酶活性以及酪氨酸酶表达的上调,在激活cAMP反应元件结合蛋白 (CREB) 和细胞外信号调节激酶类型1和2 (ERK1/2) 之前。这些结果表明,类黄酮的4 '-O-甲基通过上调小鼠B16F10黑素瘤细胞的磷酸化CREB激活其主要信号转导途径,在黑素生成的诱导中起重要作用。
  • 【引产过程中与潜伏期长度相关的因素。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejogrb.2006.09.002 复制DOI
    作者列表:Grobman WA,Simon C
    BACKGROUND & AIMS: OBJECTIVE:To evaluate the factors that are associated with the length of the latent phase during labor induction in nulliparous women. STUDY DESIGN:During a 6-month period, all nulliparous women with a viable fetus of at least 36 weeks gestation who underwent induction of labor were identified. Demographic and intrapartum data were abstracted from the medical record. In an effort to understand the association of different factors with the length of the latent phase, both univariable and multivariable analyses were employed. RESULTS:The median length of the latent phase for the women available for analysis (N=397) was 384 min with an interquartile range of 240-604 min. In univariable analysis, a greater maternal age, a medical indication for induction, and unripe cervical status at admission (assessed by either modified Bishop score or use of cervical ripening agents) were significantly associated with a latent phase of at least 12 h. In multivariable analysis, the only variables that continued to be independently associated with a latent phase of at least 12 h were modified Bishop scores of 0-2 (adjusted odds ratio 42.0, 95% confidence interval 9.7, 183.2) and 3-5 (adjusted odds ratio 9.3, 95% confidence interval 2.1, 40.9). CONCLUSION:A woman's modified Bishop score at admission for labor induction, but not other risk factors typically associated with cesarean, is associated with length of the latent phase.
    背景与目标:
  • 【日光氖激光辐射诱导绵羊外周血单核细胞的姐妹染色单体交换。】 复制标题 收藏 收藏
    DOI:10.1016/s0027-5107(97)00060-2 复制DOI
    作者列表:Ocaña Quero JM,Gomez Villamandos R,Moreno Millán M,Santisteban Valenzuela JM
    BACKGROUND & AIMS: The effects of laser light on the cellular DNA have not been extensively characterized. Low-power laser sources, such as the helium-neon (He-Ne) laser with a wavelength of 632.8 nm, have been found to produce photobiological and photodamage effects with evidence of interference with cell replication. We have investigated the effects of He-Ne laser irradiation on sister chromatid exchange (SCE) frequencies in sheep peripheral blood mononuclear cells (PBMC). Cultured cells were irradiated once at 6 selected energy intensities of laser irradiation and then stimulated with pokeweed mitogen and cultured in the presence of 5-bromodeoxyuridine (BrdUrd). The frequency of SCEs of both irradiated and non-irradiated cells were analyzed. The mean SCE of irradiated cells significantly increased with growing energy density up to a laser dose of 24 J/cm2, whereas after an energy density of 24 J/cm2, the SCE frequency decreased with increasing energy densities. We concluded that the application of He-Ne laser irradiation at energy densities ranging from 2 to 96 J/cm2 produced a different effect on SCE frequency in sheep PBMC in vitro.

    背景与目标: 激光对细胞DNA的影响尚未得到广泛表征。已发现低功率激光源,例如波长为632.8 nm的氦氖 (He-Ne) 激光器,可产生光生物学和光损伤效应,并具有干扰细胞复制的证据。我们已经研究了He-Ne激光照射对绵羊外周血单核细胞 (PBMC) 中姐妹染色单体交换 (SCE) 频率的影响。以6种选定的激光照射能量强度照射培养的细胞一次,然后用商陆有丝分裂原刺激并在5-溴脱氧尿苷 (BrdUrd) 存在下培养。分析了辐照和非辐照细胞的sce频率。辐照细胞的平均SCE随着能量密度的增长而显着增加,直到激光剂量为24 J/cm2,而在能量密度为24 J/cm2之后,SCE频率随着能量密度的增加而降低。我们得出的结论是,在2至96 J/cm2的能量密度下应用He-Ne激光辐照对体外绵羊PBMC的SCE频率产生了不同的影响。
  • 【谷氨酸受体和基因诱导: 从受体到细胞核的信号传导。】 复制标题 收藏 收藏
    DOI:10.1016/s0898-6568(96)00134-9 复制DOI
    作者列表:Lerea LS
    BACKGROUND & AIMS: Activation of glutamate receptors has been linked to a diversity of lasting physiologic and pathologic changes in the mammalian nervous system. The cellular and molecular mechanisms underlying permanent modifications of nervous system structure and function following brief episodes of neuronal activity are unknown. Immediate early genes (IEGs) have been implicated in the conversion of short-term stimuli to long-term changes in cellular phenotype by regulation of gene expression. Many of the long-term consequences of glutamate receptor activation correlate with increases in specific IEGs; the intracellular signalling pathways coupling activation of receptors at the cell surface with induction of IEGs in the nucleus are incompletely understood. Analysis of mechanisms of how extracellular factors control gene expression implicate activation of second messenger systems and protein kinases. Activation of glutamate receptors results in an initial increase in intracellular calcium; the route of calcium influx may differ depending on the specific receptor subtype activated. Intracellular calcium is often the first messenger in response to an extracellular stimulus and can be the trigger for activating numerous other signalling pathways. Results obtained over the past several years support a hypothesis where selective activation of distinct intracellular signalling pathways and IEG responses, following activation of different glutamate receptor subtypes, involve spatial restriction of key enzymes to sites of local calcium increases. The specificity in long-term neuronal responses following brief synaptic activation may depend on the specific intracellular signalling mechanisms triggered and the unique array of IEGs transcribed.

    背景与目标: 谷氨酸受体的激活与哺乳动物神经系统中持久的生理和病理变化的多样性有关。短暂的神经元活动后,神经系统结构和功能永久改变的细胞和分子机制尚不清楚。通过基因表达的调节,即刻早期基因 (IEGs) 与短期刺激转化为细胞表型的长期变化有关。谷氨酸受体激活的许多长期后果与特定IEGs的增加有关; 细胞表面受体激活与细胞核IEGs诱导耦合的细胞内信号传导途径尚不完全了解。分析细胞外因子如何控制基因表达的机制暗示第二信使系统和蛋白激酶的激活。谷氨酸受体的激活导致细胞内钙的初始增加; 钙流入的途径可能因激活的特定受体亚型而异。细胞内钙通常是响应细胞外刺激的第一信使,并且可能是激活许多其他信号通路的触发因素。在过去几年中获得的结果支持了一个假设,即不同的谷氨酸受体亚型激活后,选择性激活不同的细胞内信号传导途径和IEG反应涉及关键酶对局部钙位点的空间限制增加。短暂突触激活后长期神经元反应的特异性可能取决于触发的特定细胞内信号传导机制和转录的独特IEGs阵列。
  • 【p53抑癌基因和Fas/Apo-1在诱导癌细胞凋亡和分化中的作用。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Takahashi R
    BACKGROUND & AIMS: :Recent studies have suggested that wild-type p53 blocks cell cycle progression near the G1-S boundary and is involved in both differentiation and apoptosis in many types of cells including cancer cells. p53 expression is enhanced upon DNA-damaging apoptotic stimuli while Fas/Apo-1, a member of the tumor necrosis factor receptor family expressed on cell surface, transduces a signal for apoptosis upon specific ligand or antibody engagement. We demonstrated that stable transfection of the wild-type p53 gene under the control of CMV promoter induced differentiation and apoptosis under restricted conditions in cancer cells, and often caused sensitization of p53-transfected cells to Fas/Apo-1 signal. To investigate the interaction between two major apoptotic pathways involving p53 and Fas/Apo-1 we have established a system that allows to induce wild-type p53 overexpression and apoptosis in cancer cells upon treatment with anti-Fas antibody. The system also allows to investigate other factors interacting with p53 and Fas/Apo-1, and should provide a clue to understanding the biological and biochemical aspects of apoptosis.
    背景与目标: : 最近的研究表明,野生型p53阻断G1-S边界附近的细胞周期进程,并参与包括癌细胞在内的许多类型细胞的分化和凋亡。p53表达在破坏DNA的凋亡刺激时增强,而Fas/Apo-1 (在细胞表面表达的肿瘤坏死因子受体家族的成员) 在特异性配体或抗体接合时转导凋亡信号。我们证明,在CMV启动子控制下,野生型p53基因的稳定转染可在限制条件下诱导癌细胞的分化和凋亡,并经常引起p53-transfected细胞对Fas/Apo-1信号的敏感性。为了研究涉及p53和Fas/Apo-1的两个主要凋亡途径之间的相互作用,我们建立了一个系统,该系统允许在用抗Fas抗体治疗后诱导野生型p53过表达和癌细胞凋亡。该系统还允许研究与p53和Fas/Apo-1相互作用的其他因素,并且应该为了解凋亡的生物学和生化方面提供线索。
  • 【通过将顺铂与携带TRAIL的溶瘤腺病毒结合,协同诱导肿瘤细胞死亡。】 复制标题 收藏 收藏
    DOI:10.1007/s11010-007-9514-6 复制DOI
    作者列表:Pan Q,Liu B,Liu J,Cai R,Wang Y,Qian C
    BACKGROUND & AIMS: :Chemoresistance and side effects are considered as the major obstacles in cisplatin-based chemotherapy of various human malignant tumors. Conjugation with cancer-specific apoptotic stimuli TRAIL or typical viro-agent ONYX-015 has been extensively investigated to enhance the antitumor activity of cisplatin. In this study, we presented a novel chemo-gene-virotherapeutic strategy to further improve the toxic effects in cancer cells and reduce the damage in normal cells. Here, an oncolytic adenoviral vector (ZD55), with a deletion of E1B 55-kDa gene, was employed to express the therapeutic TRAIL gene by constructing a recombinant virus ZD55-TRAIL. Exogenous gene delivery efficacy was determined by both in vitro and in vivo experiments and enhanced cytotoxicity of combined treatment of ZD55-TRAIL with cisplatin was evaluated in several cancer cell lines. Moreover, negative effects on normal cells have been tested in both L-02 and MRC-5 cell lines by MTT assay and apoptotic cell staining. According to our observation, combination of ZD55-TRAIL with cisplatin exhibited an apparent synergistic cytotoxicity in cancer cells, yet significantly abolished the negative toxicity in normal cells by reducing the dosage. Thus, a novel chemo-gene-virotherapeutic strategy for cancer therapy was proposed.
    背景与目标: : 化学耐药性和副作用被认为是各种人类恶性肿瘤基于顺铂的化学疗法的主要障碍。已广泛研究了与癌症特异性凋亡刺激TRAIL或典型病毒试剂ONYX-015的结合,以增强顺铂的抗肿瘤活性。在这项研究中,我们提出了一种新的化学基因-病毒治疗策略,以进一步改善癌细胞的毒性作用并减少正常细胞的损伤。在这里,使用具有E1B 55-kda基因缺失的溶瘤腺病毒载体 (ZD55) 通过构建重组病毒ZD55-TRAIL来表达治疗性TRAIL基因。通过体外和体内实验确定外源基因递送功效,并在几种癌细胞系中评估了ZD55-TRAIL与顺铂联合治疗的增强的细胞毒性。此外,已经通过MTT分析和凋亡细胞染色在L-02和MRC-5细胞系中测试了对正常细胞的负面影响。根据我们的观察,ZD55-TRAIL与顺铂的组合在癌细胞中表现出明显的协同细胞毒性,但通过减少剂量显着消除了正常细胞中的负毒性。因此,提出了一种用于癌症治疗的新型化学基因-病毒治疗策略。
  • 【刺激AMP激活的蛋白激酶对于苯巴比妥在人和小鼠肝脏中诱导药物代谢酶至关重要。】 复制标题 收藏 收藏
    DOI:10.1124/mol.106.029421 复制DOI
    作者列表:Rencurel F,Foretz M,Kaufmann MR,Stroka D,Looser R,Leclerc I,da Silva Xavier G,Rutter GA,Viollet B,Meyer UA
    BACKGROUND & AIMS: :Our previous studies have suggested a role for AMP-activated protein kinase (AMPK) in the induction of CYP2B6 by phenobarbital (PB) in hepatoma-derived cells (Rencurel et al., 2005). In this study, we showed in primary human hepatocytes that: 1) 5'-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside and the biguanide metformin, known activators of AMPK, dose-dependently increase the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB. 2) PB, but not the human nuclear receptor constitutive active/androstane receptor (CAR) ligand 6-(4-chlorophenyl)imidazol[2,1-6][1,3]thiazole-5-carbaldehyde, dose-dependently increase AMPK activity. 3) Pharmacological inhibition of AMPK activity with compound C or dominant-negative forms of AMPK blunt the inductive response to phenobarbital. Furthermore, in transgenic mice with a liver-specific deletion of both the alpha1 and alpha2 AMPK catalytic subunits, basal levels of Cyp2b10 and Cyp3a11 mRNA were increased but not in primary culture of mouse hepatocytes. However, phenobarbital or 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene, a mouse CAR ligand, failed to induce the expression of these genes in the liver or cultured hepatocytes from mice lacking hepatic expression of the alpha1 and alpha2 subunits of AMPK. The distribution of CAR between the nucleus and cytosol was not altered in hepatocytes from mice lacking both AMPK catalytic subunits. These data highlight the essential role of AMPK in the CAR-mediated signal transduction pathway.
    背景与目标: : 我们先前的研究表明,AMP激活的蛋白激酶 (AMPK) 在苯巴比妥 (PB) 在肝癌衍生细胞中诱导CYP2B6中的作用 (rencorel等人,2005)。在这项研究中,我们在原代人类肝细胞中显示: 1) 5 '-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-β-d-呋喃核苷和双胍二甲双胍 (已知的AMPK激活剂) 剂量依赖性地增加CYP2B6和CYP3A4的表达与PB相似的程度。2) PB,但不是人核受体组成型活性/雄甾烷受体 (CAR) 配体6-(4-氯苯基) 咪唑 [2,1-6][1,3]thiazole-5-carbaldehyde,剂量依赖性地增加AMPK活性。3) 用化合物C或AMPK的显性阴性形式对AMPK活性的药理抑制钝化对苯巴比妥的诱导反应。此外,在具有肝脏特异性的 α1和 α2 AMPK催化亚基缺失的转基因小鼠中,Cyp2b10和Cyp3a11 mRNA的基础水平增加,但在小鼠肝细胞的原代培养中却没有。然而,苯巴比妥或1,4双 [2-(3,5-二氯吡啶基氧基)] 苯 (一种小鼠CAR配体) 未能诱导这些基因在肝脏或培养的肝细胞中的表达,这些基因来自缺乏AMPK的 α1和 α2亚基的肝表达的小鼠。缺乏两个AMPK催化亚基的小鼠的肝细胞中,核与胞质之间的CAR分布没有改变。这些数据强调了AMPK在CAR介导的信号转导途径中的重要作用。
  • 【NMDA受体介导皮质损伤后fos和fos相关抗原的皮质诱导。】 复制标题 收藏 收藏
    DOI:10.1016/s0014-4886(05)80023-8 复制DOI
    作者列表:Sharp JW,Sagar SM,Hisanaga K,Jasper P,Sharp FR
    BACKGROUND & AIMS: :Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.
    背景与目标: : 皮质腔病变和侧脑室注射喹啉酸 (一种NMDA受体激动剂) 以相似的方式在同侧成年大鼠大脑皮层中诱导Fos和Fos相关抗原 (fra)。使用原位杂交评估的c-fos mRNA在1小时内被诱导,并在皮质病变后3至8小时内消失。使用特异性单克隆抗体检测到的Fos蛋白在1小时内被诱导,并在皮质病变后4小时消失。使用多克隆抗体检测到的FRA蛋白在1至4小时之间被诱导,并在局灶性皮质损伤后持续至少72小时。脑室内注射CPP (一种竞争性NMDA受体拮抗剂) 完全阻断了局灶性皮质病变同侧皮质中这些核蛋白的诱导-除了损伤部位本身周围。脑室内注射非NMDA谷氨酸类似物quisqualate会在海马中诱导Fos,但在皮质中不诱导Fos。这些数据表明,NMDA受体介导皮质损伤后Fos和fra的诱导。有人提出,局部皮层损伤会释放起NMDA受体作用的兴奋性氨基酸,从而引发扩散抑制,并且由此产生的去极化会在整个皮层的神经元中诱导Fos。由于Fos和fra是调节靶基因表达的蛋白质,因此它们可以介导皮层损伤后神经元的长期生化适应。
  • 【Alfathesin用于剖腹产麻醉诱导。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Mahomedy MC,Downing JW,Mahomedy YH
    BACKGROUND & AIMS: :Anaesthesia was induced with Alfathesin (60 - 70 mul/kg) in 50 healthy mothers undergoing elective Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. The mothers were tilted laterally throughout the operation. Blood gas studies done on the mothers before induction and at delivery, revealed a mild respiratory alkalosis associated with a moderate degree of metabolic acidosis, which appeared to increase during anaesthesia. Umbilical cord blood gas analyses indicated a mild degree of fetal respiratory acidosis (mean pCO2 Uv 45,3
    背景与目标: : 在接受选择性剖腹产的50名健康母亲中,用Alfathesin (60 - 70 mul/kg) 诱导麻醉。用一氧化二氮,氧气,肌肉松弛剂和受控通气维持麻醉。母亲在整个手术过程中横向倾斜。在诱导前和分娩时对母亲进行的血气研究显示,轻度呼吸性碱中毒与中度代谢性酸中毒相关,在麻醉期间似乎有所增加。脐带血气分析表明胎儿呼吸性酸中毒程度较轻 (平均pCO2 Uv 45,3
  • 【迷迭香酸通过抑制肝星状细胞活化/增殖和诱导凋亡来减弱肝纤维化。】 复制标题 收藏 收藏
    DOI:10.1016/j.apjtm.2017.05.012 复制DOI
    作者列表:El-Lakkany NM,El-Maadawy WH,Seif El-Din SH,Hammam OA,Mohamed SH,Ezzat SM,Safar MM,Saleh S
    BACKGROUND & AIMS: OBJECTIVE:To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo. METHODS:The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined. RESULTS:RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC50 of 276 μg/mL and 171 μg/mL for 24 h and 48 h, respectively, with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT, AST, oxidative stress markers and reduced TIMP-1, HP levels, inflammatory markers and fibrosis score (S1 vs S4). Furthermore, reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded. CONCLUSIONS:RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture.
    背景与目标:
  • 【人内脂素基因的低氧诱导是由低氧诱导因子-1直接介导的。】 复制标题 收藏 收藏
    DOI:10.1016/j.febslet.2006.06.052 复制DOI
    作者列表:Bae SK,Kim SR,Kim JG,Kim JY,Koo TH,Jang HO,Yun I,Yoo MA,Bae MK
    BACKGROUND & AIMS: :Visfatin has been originally identified as a growth factor for early stage B cells and recently known as an adipokine. Here, we report that hypoxia induces the visfatin mRNA and protein levels in MCF7 breast cancer cells. We also demonstrate that induction of visfatin gene is regulated by hypoxia-inducible factor-1alpha (HIF-1alpha). Moreover, 5'-flanking promoter region of human visfatin gene contains two functional HIF responsive elements (HREs), activating the expression of visfatin. Mutation of these HREs in the visfatin promoter abrogates activation of a luciferase reporter gene driven by visfatin promoter under hypoxia. Taken together, our results demonstrate that visfatin is a new hypoxia-inducible gene of which expression is stimulated through the interaction of HIF-1 with HRE sites in its promoter region.
    背景与目标: : Visfatin最初被确定为早期b细胞的生长因子,最近被称为脂肪因子。在这里,我们报告了缺氧诱导MCF7乳腺癌细胞中的visfatin mRNA和蛋白质水平。我们还证明了内脂素基因的诱导受缺氧诱导factor-1alpha (HIF-1alpha) 的调节。此外,人visfatin基因的5' 侧翼启动子区域包含两个功能性HIF响应元件 (HREs),激活visfatin的表达。这些hre在内脂素启动子中的突变会在缺氧条件下废除由内脂素启动子驱动的荧光素酶报告基因的激活。总之,我们的结果表明,visfatin是一种新的缺氧诱导基因,其表达通过HIF-1与其启动子区域中的HRE位点相互作用而被刺激。
  • 【PDGF信号在眼科三叉神经胎盘诱导中的重要作用。】 复制标题 收藏 收藏
    DOI:10.1242/dev.017954 复制DOI
    作者列表:McCabe KL,Bronner-Fraser M
    BACKGROUND & AIMS: :Much of the peripheral nervous system of the head is derived from ectodermal thickenings, called placodes, that delaminate or invaginate to form cranial ganglia and sense organs. The trigeminal ganglion, which arises lateral to the midbrain, forms via interactions between the neural tube and adjacent ectoderm. This induction triggers expression of Pax3, ingression of placode cells and their differentiation into neurons. However, the molecular nature of the underlying signals remains unknown. Here, we investigate the role of PDGF signaling in ophthalmic trigeminal placode induction. By in situ hybridization, PDGF receptor beta is expressed in the cranial ectoderm at the time of trigeminal placode formation, with the ligand PDGFD expressed in the midbrain neural folds. Blocking PDGF signaling in vitro results in a dose-dependent abrogation of Pax3 expression in recombinants of quail ectoderm with chick neural tube that recapitulate placode induction. In ovo microinjection of PDGF inhibitor causes a similar loss of Pax3 as well as the later placodal marker, CD151, and failure of neuronal differentiation. Conversely, microinjection of exogenous PDGFD increases the number of Pax3+ cells in the trigeminal placode and neurons in the condensing ganglia. Our results provide the first evidence for a signaling pathway involved in ophthalmic (opV) trigeminal placode induction.
    背景与目标: : 头部的许多周围神经系统来自外胚层增厚,称为placodes,其分层或内陷形成颅神经节和感觉器官。三叉神经节出现在中脑外侧,是通过神经管与相邻外胚层之间的相互作用形成的。这种诱导触发Pax3的表达,胎盘细胞的进入及其向神经元的分化。然而,潜在信号的分子性质仍然未知。在这里,我们研究PDGF信号在眼科三叉神经胎盘诱导中的作用。通过原位杂交,PDGF受体 β 在三叉神经胎盘形成时在颅外胚层中表达,配体PDGFD在中脑神经褶皱中表达。体外阻断PDGF信号传导导致鹌鹑外胚层重组体中Pax3表达的剂量依赖性废除,鸡鸡神经管概括了胎盘诱导。在ovo中,PDGF抑制剂的显微注射会导致类似的Pax3丢失以及后来的胎盘标记CD151和神经元分化失败。相反,微量注射外源PDGFD会增加三叉神经节中Pax3细胞的数量和凝结神经节中的神经元的数量。我们的结果为参与眼科 (opV) 三叉神经节胎盘诱导的信号通路提供了第一个证据。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录