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：

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。

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。

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。

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。

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。

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。

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

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：

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。

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。

BACKGROUND & AIMS: :During embryogenesis, dental trigeminal axon navigation and patterning in the developing tooth take place in a highly spatio-temporally directed manner that is tightly linked to tooth morphogenesis and cell differentiation. Tooth formation is regulated by sequential and reciprocal tissue interactions between dental epithelium and neural crest-derived ectomesenchymal cells. This odontogenic secondary induction is mediated by signal molecules of different conserved families. Recent molecular and experimental data have provided evidence that local instructive signaling from the early odontogenic epithelium also controls dental axon navigation in the dental mesenchyme. In this review, we discuss recent molecular data regarding tooth formation and innervation and the putative role of the secondary induction in coordinating these two developmental processes. Importantly, because it has not yet been shown that the interactions that regulate tooth innervation include signaling to the dental epithelium and that they are reciprocal, it remains to be demonstrated that secondary induction controls the establishment of tooth nerve supply. Moreover, the key question of which molecule(s), if any, integrate tooth morphogenesis and the development of dental sensory trigeminal innervation remains to be answered.

背景与目标： : 在胚胎发生过程中，发育中的牙齿中的三叉神经轴突导航和图案化以高度时空定向的方式发生，这与牙齿的形态发生和细胞分化紧密相关。牙齿形成受牙齿上皮与神经嵴来源的外胚间充质细胞之间的顺序和相互组织相互作用的调节。这种牙源性次级诱导是由不同保守家族的信号分子介导的。最近的分子和实验数据提供了证据，表明来自早期牙源性上皮的局部指导性信号也控制了牙间充质中的牙轴突导航。在这篇综述中，我们讨论了有关牙齿形成和神经支配的最新分子数据，以及次级诱导在协调这两个发育过程中的假定作用。重要的是，由于尚未显示出调节牙齿神经支配的相互作用包括对牙齿上皮的信号传导，并且它们是相互的，因此仍有待证明，二次诱导控制牙齿神经供应的建立。此外，哪个分子 (如果有的话) 整合牙齿形态发生和牙齿感觉三叉神经支配的发展的关键问题仍有待回答。

BACKGROUND & AIMS: :Heart development begins with the induction of cardiogenic cells from the embryonic mesoderm, followed by the coalescing of these cells into a linear heart tube. Subsequent looping of the heart tube brings the rudimentary atria and ventricles into alignment for further development into the four-chambered heart. Underlying these morphologic events is a complex program of signaling between cells and tissues that orchestrates their participation in heart development. Among these signals are bone morphogenetic proteins, fibroblast growth factors, Wnts, Hedgehog, and members of the transforming growth factor-beta family of signaling molecules. We review here the various properties of these signaling molecules and their signal transduction pathways in hopes of providing a greater appreciation of the molecular events driving heart development.

背景与目标： : 心脏发育始于从胚胎中胚层诱导心源性细胞，然后将这些细胞聚结到线性心管中。随后的心管循环使基本的心房和心室对齐，以进一步发展为四腔心脏。这些形态学事件的基础是细胞和组织之间的复杂信号程序，这些程序协调了它们参与心脏发育的过程。这些信号包括骨形态发生蛋白，成纤维细胞生长因子，Wnts，刺猬和信号分子转化生长因子-β 家族的成员。我们在这里回顾了这些信号分子的各种特性及其信号转导途径，希望对驱动心脏发育的分子事件有更大的了解。

BACKGROUND & AIMS: :Olig2 protein, a member of the basic helix-loop-helix transcription factor family, was introduced into the mouse embryonic carcinoma cell line P19 for induction of motor neuron differentiation. We show that Olig2 protein has the ability to permeate the cell membrane without the addition of a protein transduction domain (PTD), similar to other basic helix-loop-helix transcription factors such as MyoD and NeuroD2. Motor neuron differentiation was evaluated for the elongation of neurites and the expression of choline acetyltransferase (ChAT) mRNA, a differentiation marker of motor neurons. By addition of Olig2 protein, motor neuron differentiation was induced in P19 cells.

背景与目标： : Olig2蛋白是基本螺旋-环-螺旋转录因子家族的成员，已被引入小鼠胚胎癌细胞系P19中，以诱导运动神经元分化。我们表明，Olig2蛋白具有在不添加蛋白质转导结构域 (PTD) 的情况下渗透细胞膜的能力，类似于其他基本螺旋-环-螺旋转录因子，例如MyoD和neurod2。评估运动神经元分化的神经突延伸和胆碱乙酰转移酶 (ChAT) mRNA (运动神经元的分化标记) 的表达。通过添加Olig2蛋白，在P19细胞中诱导运动神经元分化。

BACKGROUND & AIMS: :Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins and thromboxanes from free arachidonic acid. Increasing evidence suggests that COX-2 plays a role in tumorigenesis. A variety of stimuli induce COX-2 and it is overexpressed in many tumors, including non-small cell lung cancer (NSCLC). We studied the regulation of COX-2 expression in immortalized human bronchial epithelial cells (HBECs) by transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) because these two growth factors are present in both the pulmonary milieu of those at risk for lung cancer as well as in the tumor microenvironment. EGF significantly enhanced TGF-beta1-mediated induction of COX-2 and corresponding prostaglandin E2 (PGE2) production. TGF-beta1 and EGF induced COX-2 at the transcriptional and post-transcriptional levels. EGF receptor (EGFR) inhibition, neutralizing antibody against amphiregulin, or mitogen-activated protein kinase kinase (MEK) inhibition blocked TGF-beta1-mediated COX-2 induction. COX-2 induction by TGF-beta1 depended upon Smad3 signaling and required the activity of EGFR or its downstream mediators. Autocrine amphiregulin signaling maintains EGFR in a constitutively active state in HBECs, allowing for COX-2 induction by TGF-beta1. Thus, EGFR ligands, which are abundant in the pulmonary microenvironment of those at risk for lung cancer, potentiate and are required for COX-2 induction by TGF-beta1 in HBEC. These findings emphasize the central role of EGFR signaling in COX-2 induction by TGF-beta1 and suggest that inhibition of EGFR signaling should be investigated further for lung cancer prevention.

背景与目标： : Cyclooxygenase-2 (COX-2) 是从游离花生四烯酸生产前列腺素和血栓素的关键酶。越来越多的证据表明，COX-2在肿瘤发生中起作用。多种刺激可诱导COX-2，并且在许多肿瘤中过度表达，包括非小细胞肺癌 (NSCLC)。我们研究了转化生长factor-beta1 (TGF-beta1) 和表皮生长因子 (EGF) 对永生化人支气管上皮细胞 (hbec) 中COX-2表达的调节，因为这两种生长因子存在于肺癌风险人群的肺环境中以及肿瘤微环境中。EGF显着增强了TGF-beta1-mediated诱导的COX-2和相应的前列腺素E2 (PGE2) 产生。TGF-beta1和EGF在转录和转录后水平诱导COX-2。EGF受体 (EGFR) 抑制、抗双调蛋白中和抗体或丝裂原活化蛋白激酶激酶 (MEK) 抑制TGF-beta1-mediated COX-2诱导阻断。TGF-beta1诱导的COX-2依赖于Smad3信号传导，需要EGFR或其下游介质的活性。自分泌双调蛋白信号在hbec中维持EGFR处于组成型活性状态，允许TGF-beta1诱导COX-2。因此，EGFR配体 (其在具有肺癌风险的那些人的肺微环境中丰富) 增强并且是通过HBEC中的TGF-beta1诱导COX-2所必需的。这些发现强调了EGFR信号在TGF-beta1诱导COX-2中的核心作用，并表明应进一步研究EGFR信号的抑制作用以预防肺癌。