• 【精子发生不需要局部产生卵泡抑素。】 复制标题 收藏 收藏
    DOI:10.1530/rep.1.01172 复制DOI
    作者列表:Lin SY,Morrison JR,Matzuk MM,de Kretser DM
    BACKGROUND & AIMS: :It has been proposed that follistatin can modulate the actions of activins and/or other members of the transforming growth factor-beta superfamily of proteins on testicular function, since mice overexpressing follistatin showed spermatogenic disruption. However, since mice with targeted disruption of the follistatin gene die soon after birth, it is not feasible to determine the effect of the absence of follistatin on testicular function using this model. To further understand the role of follistatin on the development and maintenance of spermatogenesis, fetal testes, collected by Caesarean section at day 18 of gestation from follistatin null mice, were transplanted to the external ear of castrated recombination activating gene 1 immunocompromised male mice. The testicular grafts were then analysed 7-8 weeks after transplantation and showed that full spermatogenesis developed in both the testes of wild-type and follistatin null mice. This study indicates that, if follistatin is required to modulate spermatogenic development, it is not supplied by local testicular production but by circulating follistatin from the host mouse.
    背景与目标: : 已经提出,卵泡抑素可以调节激活素和/或蛋白质的转化生长因子-β 超家族的其他成员对睾丸功能的作用,因为过度表达卵泡抑素的小鼠表现出生精破坏。但是,由于具有靶向破坏卵泡抑素基因的小鼠在出生后不久就死亡,因此使用该模型确定不存在卵泡抑素对睾丸功能的影响是不可行的。为了进一步了解卵泡抑素在精子发生的发展和维持中的作用,将卵泡抑素无效小鼠在妊娠第18天通过剖腹产收集的胎儿睾丸移植到去势重组激活基因1免疫功能低下的雄性小鼠的外耳。然后在移植后7-8周对睾丸移植物进行分析,结果表明,野生型和卵泡抑制素无效小鼠的睾丸均发育了完全的精子发生。这项研究表明,如果需要卵泡抑素来调节生精发育,则不是由本地睾丸产生而是由宿主小鼠循环卵泡抑素提供的。
  • 【瘦素通过下丘脑控制脂联素的产生。】 复制标题 收藏 收藏
    DOI:10.1016/j.mehy.2006.06.031 复制DOI
    作者列表:Huypens P
    BACKGROUND & AIMS: :Adipocyte generated endocrine signals, including leptin and adiponectin, control systemic insulin sensitivity as part of a broader control mechanism in energy balance. Leptin and adiponectin are inversely regulated in vivo, but not in vitro, suggesting that the inverse relationship is mediated via indirect mechanisms. The cytokine TNF-alpha has been proposed as a putative candidate in the reciprocal regulation of adiponectin and leptin. However, several recent findings, including the observation that adiponectin production is paradoxically increased in mouse models with selective hypothalamic leptin resistance, indicate that part of the inverse relationship between leptin and adiponectin is mediated via a neural interface. Therefore, we propose that adiponectin production is, at least in part, controlled by the hypothalamic actions of leptin.
    背景与目标: 脂肪细胞产生的内分泌信号,包括瘦素和脂联素,控制全身胰岛素敏感性,作为能量平衡更广泛控制机制的一部分。瘦素和脂联素在体内是反向调节的,但在体外不是反向调节的,这表明这种反向关系是通过间接机制介导的。已提出细胞因子TNF-α 作为脂联素和瘦素相互调节的假定候选者。然而,最近的一些发现,包括观察到在具有选择性下丘脑瘦素抵抗的小鼠模型中脂联素的产生反常增加,表明瘦素和脂联素之间的反比关系的一部分是通过神经界面介导的。因此,我们建议脂联素的产生至少部分受瘦素的下丘脑作用控制。
  • 【蛋白激酶D2通过NF-κ b介导溶血磷脂酸诱导的白细胞介素8在未转化的人结肠上皮细胞中产生。】 复制标题 收藏 收藏
    DOI:10.1152/ajpcell.00308.2006 复制DOI
    作者列表:Chiu TT,Leung WY,Moyer MP,Strieter RM,Rozengurt E
    BACKGROUND & AIMS: :The signaling pathways mediating lysophosphatidic acid (LPA)-stimulated PKD(2) activation and the potential contribution of PKD(2) in regulating LPA-induced interleukin 8 (IL-8) secretion in nontransformed, human colonic epithelial NCM460 cells were examined. Treatment of serum-deprived NCM460 cells with LPA led to a rapid and striking activation of PKD(2), as measured by in vitro kinase assay and phosphorylation at the activation loop (Ser706/710) and autophosphorylation site (Ser876). PKD(2) activation induced by LPA was abrogated by preincubation with selective PKC inhibitors GF-I and Ro-31-8220 in a dose-dependent manner. These inhibitors did not have any direct inhibitory effect on PKD(2) activity. LPA induced a striking increase in IL-8 production and stimulated NF-kappaB activation, as measured by NF-kappaB-DNA binding, NF-kappaB-driven luciferase reporter activity, and IkappaBalpha phosphorylation. PKD(2) gene silencing utilizing small interfering RNAs targeting distinct PKD(2) sequences dramatically reduced LPA-stimulated NF-kappaB promoter activity and IL-8 production. PKD(2) activation is a novel early event in the biological action of LPA and mediates LPA-stimulated IL-8 secretion in NCM460 cells through a NF-kappaB-dependent pathway. Our results demonstrate, for the first time, the involvement of a member of the PKD family in the production of IL-8, a potent proinflammatory chemokine, by epithelial cells.
    背景与目标: : 检测了介导溶血磷脂酸 (LPA) 刺激的PKD(2) 激活的信号通路,以及PKD(2) 在调节LPA诱导的白介素8 (IL-8) 分泌中的潜在作用。未转化的人结肠上皮NCM460细胞。用LPA处理血清剥夺的NCM460细胞导致PKD(2) 的快速和惊人的激活,如通过体外激酶测定和激活环 (Ser706/710) 和自磷酸化位点 (Ser876) 测量的。通过与选择性PKC抑制剂gf-i预孵育消除LPA诱导的PKD(2) 激活,并以剂量依赖性方式Ro-31-8220。这些抑制剂对PKD(2) 活性没有任何直接抑制作用。通过NF-κ b-DNA结合,NF-κ b驱动的荧光素酶报告活性和ikappaba磷酸化来测量,LPA诱导了IL-8产生的显着增加并刺激了NF-κ b活化。利用靶向不同PKD(2) 序列的小干扰rna沉默PKD(2) 基因显著降低LPA刺激的NF-κ b启动子活性和IL-8产生。PKD(2) 激活是LPA生物学作用中的一个新的早期事件,并通过NF-κ b依赖性途径介导NCM460细胞中LPA刺激的IL-8分泌。我们的结果首次证明了PKD家族成员参与了上皮细胞产生IL-8 (一种有效的促炎趋化因子)。
  • 【意大利北部地区的综合废物管理: 堆肥生产和使用以及堆肥,土壤和作物的分析控制。】 复制标题 收藏 收藏
    DOI:10.1080/03601230600857031 复制DOI
    作者列表:Guerini G,Maffeis P,Allievi L,Gigliotti C
    BACKGROUND & AIMS: :Agricultural soils of two Italian maize farms were treated for five years with an industrially produced high-quality compost. Cattle manure and the usual mineral fertilizer were used for comparison purposes. The effects of the organic and mineral fertilizer treatments were studied by analyzing the compost and manure, cultured soils, and harvested material. The grain yield was also determined. Organic fertilization improved soil pH, CEC, content of organic matter and NPK. Soil respiration and N mineralization were found to be higher than in the purely mineral-treated soil. Plant K take-up was improved, whereas grain yield was not affected. It was confirmed that organic fertilization, particularly compost use, maintained and increased soil fertility. The study demonstrated the feasibility of using in loco analytical facilities to follow the entire recycling process-from waste to compost production-and the use of the final product in the field.
    背景与目标: : 意大利两个玉米农场的农业土壤用工业生产的高质量堆肥处理了五年。牛粪和通常的矿物肥料用于比较目的。通过分析堆肥和肥料,培养的土壤和收获的材料,研究了有机和矿物肥料处理的效果。还确定了谷物产量。有机施肥改善了土壤pH,CEC,有机质和NPK的含量。发现土壤呼吸作用和氮矿化作用高于纯矿物处理的土壤。提高了植物的K用量,而不影响谷物产量。已经证实,有机施肥,特别是堆肥的使用,可以维持和提高土壤肥力。该研究证明了在loco分析设施中使用从废物到堆肥生产的整个回收过程以及在现场使用最终产品的可行性。
  • 【B细胞慢性淋巴细胞白血病患者T细胞中的信号分子和细胞因子产生: 氟达拉滨和阿仑单抗治疗的长期影响。】 复制标题 收藏 收藏
    DOI:10.1080/10428190600565503 复制DOI
    作者列表:Kiaii S,Choudhury A,Mozaffari F,Rezvany R,Lundin J,Mellstedt H,Osterborg A
    BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.
    背景与目标: : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链,p56lck,p59fyn,ZAP-70,PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少,但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比,接受治疗的患者中大多数信号分子的强度相对不受影响,但低于未经治疗的惰性患者。然而,在患者中表达每种信号分子的T细胞总数减少,而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中,T细胞对PHA的反应降低,但对PPD的反应降低。结果表明,尽管信号分子发生了一些变化,T细胞数量减少,但在用氟达拉滨和阿仑单抗治疗后,总体T细胞功能可能长期保持良好。
  • 【慢性伤口愈合过程中趋化因子和炎性细胞因子的变化。】 复制标题 收藏 收藏
    DOI:10.1046/j.1524-475X.1997.50405.x 复制DOI
    作者列表:Fivenson DP,Faria DT,Nickoloff BJ,Poverini PJ,Kunkel S,Burdick M,Strieter RM
    BACKGROUND & AIMS: :Wound healing is a complex process resulting from an interplay of processes including coagulation, inflammation, angiogenesis, and epithelialization. The chemokine family has been shown to contain members that are potent regulators of many of these pathways. Because we have previously shown that chemokines "pool" in biologic wound dressings, we studied the levels of CXC and CC chemokines, along with key inflammatory mediators, serially from a group of patients undergoing therapy for chronic venous leg ulcers. After 8 weeks, all patients had marked clinical healing of their ulcers (median 63.3% reduction in size) with two of 10 completely healed. Wound fluids extracted from dressings showed high levels of platelet factor-4 and interferon-gamma-inducible protein, with a trend toward increases in the ratio of the sums of the angiogenic versus angiostatic CXC chemokines (p = 0.082) in the tissues collected from the center of the ulcers during wound closure. Neutrophil-activating peptide-2 and interleukin-8 accounted for the most changes in wound fluid angiogenic chemokines, with significant differences both as compared with baseline levels and with patients' plasma level noted at various time points between weeks 0 and 8. The level of angiostatic chemokines, interferon-y inducible protein 10 and platelet-activating-4, fell most significantly between weeks 0 and 3 as compared with plasma levels. The observed shift toward angiogenic CXC chemokines suggests that effective healing in chronic venous insufficiency ulcers appears to "move" the ulcer bed toward a state more conducive to epithelialization,characteristic of the proliferative phase of wound healing. CC chemokines were also elevated at baseline in the wound fluid samples as compared with the patients' plasma levels. Macrophage inflammatory protein-1 (3 and regulated on activation, normal T expressed and secreted (RANTES) levels decreased with healing, whereas there were significant increases in the tissue levels of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 a over the first 4 weeks of therapy (p< or = 0.05 for both). Coincident with these changes was a steady increase in the ratio of interleukin-1 R/interleukin-1 receptor antagonist protein in the ulcer center tissues, which also correlated with healing (p < 0 .05) as compared with a decreasing ratio at the ulcer edge, and a biphasic response in the wound fluids. These findings suggest that advanced wound care techniques help move the ulcer from a chronic inflammatory state into one more characteristic of the late inflammatory/early proliferative phase of wound healing. Chemokines may play a critical role in the pathogenesis of chronic venous ulcers through their effects on angiogenesis and/or the progression of inflammatory reactions at the site of injury.
    背景与目标: 伤口愈合是一个复杂的过程,由凝血、炎症、血管生成和上皮形成等过程的相互作用产生。趋化因子家族已被证明包含许多这些途径的有效调节剂。因为我们以前已经表明趋化因子在生物伤口敷料中 “聚集”,所以我们连续研究了一组接受慢性静脉腿部溃疡治疗的患者的CXC和CC趋化因子以及关键炎症介质的水平。8周后,所有患者的溃疡临床愈合明显 (中位63.3% 缩小),其中10例中有2例完全愈合。从敷料中提取的伤口液显示出高水平的血小板因子-4和干扰素-γ 诱导蛋白,在伤口闭合期间从溃疡中心收集的组织中,血管生成与血管抑制CXC趋化因子 (p = 0.082) 的总和比率呈增加趋势。中性粒细胞激活肽-2和interleukin-8占伤口流体血管生成趋化因子的最大变化,与基线水平和患者血浆水平相比,在第0周和第8周之间的不同时间点存在显着差异。与血浆水平相比,血管抑制趋化因子,干扰素y诱导蛋白10和血小板活化4的水平在第0周和第3周之间下降最明显。观察到的向血管生成CXC趋化因子的转变表明,慢性静脉功能不全溃疡的有效愈合似乎使溃疡床 “移至” 更有利于上皮形成的状态,这是伤口愈合增生期的特征。与患者血浆水平相比,伤口液体样品中的CC趋化因子在基线时也升高。巨噬细胞炎性蛋白-1 (3) 和受激活调节,正常T表达和分泌 (RANTES) 水平随愈合而降低,而在治疗的前4周内,单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1 a的组织水平显着增加 (两者p <或 = 0.05)。与这些变化同时发生的是,interleukin-1 R/interleukin-1受体拮抗剂蛋白的比例在溃疡中心组织,与溃疡边缘的比率降低相比,这也与愈合相关 (p <0.05),和伤口液体中的双相反应。这些发现表明,先进的伤口护理技术有助于将溃疡从慢性炎症状态转移到伤口愈合的晚期炎症/早期增生期的另一个特征。趋化因子可能通过其对血管生成的影响在慢性静脉溃疡的发病机理中发挥关键作用和/或损伤部位炎症反应的进展。
  • 【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。
  • 【JTE-607是一种多种细胞因子产生抑制剂,可改善SCID小鼠异种移植急性髓细胞性白血病模型中的疾病。】 复制标题 收藏 收藏
    DOI:10.1016/j.exphem.2006.05.016 复制DOI
    作者列表:Uesato N,Fukui K,Maruhashi J,Tojo A,Tajima N
    BACKGROUND & AIMS: OBJECTIVE:Accumulating findings suggest that in acute myeloid leukemia (AML) patients, proinflammatory cytokines and growth factors play important roles in the proliferation and survival of AML cells in an autocrine and paracrine manner, leading to deterioration of AML. JTE-607 is a multiple cytokine inhibitor that potently suppresses production of proinflammatory cytokines. In the present study, we investigated the potency of JTE-607 as an antileukemic agent by exploiting a SCID mouse acute leukemia model. METHODS:SCID mice injected with anti-asialo-GM1 antibody were exposed to sublethal total-body irradiation at a dose of 3 Gy and then inoculated intravenously with AML cells. JTE-607 was administered using osmotic minipumps. The effects of JTE-607 on mouse survival time, human interleukin (IL)-8 levels in mouse plasma, and proportion of human CD45(+) cells in the bone marrow were studied. RESULTS:The survival time of the mice was strictly dependent on the number of U-937 cells proliferating in vivo. Administration of JTE-607 during the initial 7 days significantly prolonged survival of the mice, suggesting killing activity of JTE-607 against AML cells in vivo. Delayed administration of JTE-607 also prolonged the survival of mice bearing established leukemia with an effect comparable to the maximum tolerable dose of cytarabine. Flow cytometer analysis of bone marrow cells revealed decreased number of human CD45(+) cells. Human IL-8 level was also reduced by JTE-607. CONCLUSION:Our results indicate that JTE-607 has potential to be a new class of antileukemic drug that exerts inhibitory activities against both the proliferation and proinflammatory cytokine production of AML cells.
    背景与目标:
  • 【未能启动: 促进iNKT细胞的细胞因子分泌。】 复制标题 收藏 收藏
    DOI:10.1016/j.immuni.2006.08.012 复制DOI
    作者列表:Locksley RM
    BACKGROUND & AIMS: :In this issue of Immunity, Bezbradica et al., (2006) uncover an unsuspected role for the cytokine GM-CSF in the thymic development of invariant NKT cells, a role that licenses these cells to secrete effector cytokines upon activation in the periphery.
    背景与目标: : 在本期《免疫》中,bezbratica等人 (2006) 揭示了细胞因子gm-csf在不变NKT细胞的胸腺发育中不可怀疑的作用,该作用允许这些细胞在外围激活时分泌效应细胞因子。
  • 【粟酒裂殖酵母CBS 356细胞外麦芽糖酶的生理表征和补料批量生产。】 复制标题 收藏 收藏
    DOI:10.1111/j.1567-1364.2006.00091.x 复制DOI
    作者列表:Jansen ML,Krook DJ,De Graaf K,van Dijken JP,Pronk JT,de Winde JH
    BACKGROUND & AIMS: :The fission yeast Schizosaccharomyces pombe CBS 356 exhibits extracellular maltase activity. This activity may be of commercial interest as it exhibited a low pH optimum (3.5) and a high affinity for maltose (Km of 7.0+/-1.8 mM). N-terminal sequencing of the protein indicates that it is the product of the AGL1 gene. Regulation of this gene occurs via a derepression/repression mechanism. In sugar- or nitrogen-limited chemostat cultures, the specific rate of enzyme production (q(p)) was independent of the nature of the carbon source (i.e. glucose or maltose), but synthesis was partially repressed by high sugar concentrations. Furthermore, q(p) increased linearly with specific growth rate (mu) between 0.04 and 0.10 h(-1). The enzyme is easily mass-produced in aerobic glucose-limited fed-batch cultures, in which the specific growth rate is controlled to prevent alcoholic fermentation. In fed-batch cultures in which biomass concentrations of 83 g L(-1) were attained, the enzyme concentration reached 58,000 Units per liter culture supernatant. Extracellular maltase may be used as a dough additive in order to prevent mechanisms such as maltose-induced glucose efflux and maltose-hypersensitivity that occur in maltose-consuming Saccharomyces cerevisiae.
    背景与目标: : 裂殖酵母粟酒裂殖酵母CBS 356表现出细胞外麦芽糖酶活性。该活性可能具有商业意义,因为它表现出低的最适pH (3.5) 和对麦芽糖的高亲和力 (Km为7.0 +/-1.8 mM)。蛋白质的N端测序表明它是AGL1基因的产物。该基因的调节是通过抑制/抑制机制发生的。在糖或氮限制的恒化器培养物中,酶产生的特定速率 (q(p)) 与碳源的性质 (即葡萄糖或麦芽糖) 无关,但高糖浓度会部分抑制合成。此外,在0.04和0.10 h(-1) 之间,q(p) 随特定生长速率 (mu) 线性增加。该酶很容易在需氧葡萄糖限制的分批补料培养物中大量生产,其中控制特定的生长速率以防止酒精发酵。在生物量浓度为83g L(-1) 的分批补料培养物中,酶浓度达到每升培养上清液58,000单位。细胞外麦芽糖酶可以用作面团添加剂,以防止在消耗麦芽糖的酿酒酵母中发生的诸如麦芽糖诱导的葡萄糖外排和麦芽糖超敏反应的机制。
  • 【电刺激通过肝素生物激活的导电支架调节成骨细胞的增殖和骨蛋白的产生。】 复制标题 收藏 收藏
    DOI:10.1002/bem.21766 复制DOI
    作者列表:Meng S,Rouabhia M,Zhang Z
    BACKGROUND & AIMS: :Electrical fields are known to interact with human cells. This principle has been explored to regulate cellular activities for bone tissue regeneration. In this work, Saos-2 cells were cultured on conductive scaffolds made of biodegradable poly(L-lactide) and the heparin-containing, electrically conducting polypyrrole (PPy/HE) to study their reaction to electrical stimulation (ES) mediated through such scaffolds. Both the duration and intensity of ES enhanced cell proliferation, generating a unique electrical intensity and temporal "window" within which osteoblast proliferation was upmodulated in contrast to the downmodulation or ineffectiveness in other ES regions. The favourable ES intensity (200 mV/mm) was further investigated in terms of the gene activation and protein production of two important osteoblast markers characterised by extracellular matrix maturation and mineralisation, that is alkaline phosphatase (ALP) and osteocalcin (OC). Both genes were found activated and the relevant protein production increased significantly following ES. In contrast, ES in the down-modulation region (400 mV/mm) suppressed the production of both ALP and OC. This work demonstrated that important osteoblast markers can be modulated with specific ES parameters mediated through conductive polymer substrates, providing a unique strategy for bone tissue engineering.
    背景与目标: 已知电场与人类细胞相互作用。已探索此原理来调节骨组织再生的细胞活性。在这项工作中,将Saos-2细胞培养在由可生物降解的聚 (L-丙交酯) 和含肝素的导电聚吡咯 (PPy/HE) 制成的导电支架上,以研究它们对通过此类支架介导的电刺激 (ES) 的反应。ES的持续时间和强度都增强了细胞增殖,产生了独特的电强度和时间 “窗口”,与其他ES区域的下调或无效相反,在该窗口内对成骨细胞增殖进行了上调。进一步研究了有利的ES强度 (200  mV/mm),即两种重要的成骨细胞标志物的基因活化和蛋白质生产,其特征是细胞外基质成熟和矿化,即碱性磷酸酶 (ALP) 和骨钙素 (OC)。发现两个基因都被激活,并且在ES之后相关的蛋白质产量显着增加。相反,下调制区域 (400  mV/mm) 中的ES抑制了ALP和OC的产生。这项工作表明,重要的成骨细胞标志物可以通过导电聚合物底物介导的特定ES参数进行调节,为骨组织工程提供了独特的策略。
  • 【体外CO2-induced的ROS产生会损害SH-SY5Y神经母细胞瘤细胞的细胞周期。】 复制标题 收藏 收藏
    DOI:10.1007/s00383-012-3206-3 复制DOI
    作者列表:Montalto AS,Currò M,Russo T,Visalli G,Impellizzeri P,Antonuccio P,Arena S,Borruto FA,Scalfari G,Ientile R,Romeo C
    BACKGROUND & AIMS: PURPOSE:We evaluated in vitro the role of CO(2)-induced oxidative stress on the expression of proteins involved in cell-cycle regulation of neuroblastoma cells. METHODS:SH-SY5Y cells were exposed to CO(2) at 15 mmHg pressure (100 %) for 4 h and then moved to normal condition for 24 h. Control cells were maintained in 5 % CO(2) for the same time. ROS production was determined by fluorescent staining with H2DCF-DA. DNA damage was measured by COMET assay. p53 protein expression was analyzed by western blot and confocal laser scanning microscopy was used to evaluate its sub-cellular localization. Cyclin expression was quantified by real-time PCR and western blot. Cell-cycle analysis was performed by FACS. RESULTS:CO(2) incubation was associated with an increase in ROS production (p < 0.01), cell DNA damage mainly after 24 h (12 % increase of tail DNA content and 4-fold increase of tail length) and a significant up-regulation in p53 expression at 24 h with an intense nuclear staining. In CO(2)-treated cells, we observed an S-phase arrest in correlation with a reduction of cyclin B1 expression. CONCLUSIONS:In vitro-simulated pneumoperitoneum environment with CO(2) induces oxidative stress and cell DNA damage, leading to p53 up-regulation involved in cell-cycle arrest of neuroblastoma cells.
    背景与目标:
  • 【将非结构化的 α-突触核蛋白转化为其 α-螺旋构象会显着减弱活性氧的产生。】 复制标题 收藏 收藏
    DOI:10.1016/j.jinorgbio.2012.09.001 复制DOI
    作者列表:Zhou B,Hao Y,Wang C,Li D,Liu YN,Zhou F
    BACKGROUND & AIMS: :The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson's disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV-visible spectroscopic experiments reveal that both Cu (I) and Cu (II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured α-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194-196), α-helical α-syn stabilizes Cu (I) by more than three orders of magnitude. Through the measurements of H(2)O(2) and hydroxyl radicals (OH) in solutions containing different forms of Cu (II) (free and complexed by unstructured or α-helical α-syn), we demonstrate that the significantly enhanced Cu (I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured α-syn to its α-helical conformation in vivo could significantly attenuate the copper-modulated ROS production.
    背景与目标: : 细胞内 α-突触核蛋白 (α-syn) 蛋白的构象变化和聚集与Parkingson病 (PD) 的病理密切相关,在突触前末端高度聚集,并保留在 α-螺旋构象中。在这项研究中,圆二色性证实,加入三氟乙醇 (TFE) 后,水溶液中的原生非结构化 α-syn转化为其 α-螺旋构象。电化学和紫外可见光谱实验表明,Cu (I) 和Cu (II) 都是稳定的,前者稳定了大约两个数量级。与非结构化 α-syn (Binolfi等人,J. Am. Chem. Soc. 133 (2011) 194-196) 相比,α-螺旋 α-syn使Cu (I) 稳定超过三个数量级。通过测量含有不同形式的Cu (II) (游离并通过非结构化或 α-螺旋 α-syn络合) 的溶液中的H(2)O(2) 和羟基自由基 (OH),我们证明了显着增强的Cu (I) 结合亲和力有助于抑制高毒性活性氧的产生,尤其是羟基自由基。我们的研究提供了有力的证据,表明作为防止神经元细胞损伤的一种可能手段,在体内将非结构化的 α-syn转化为其 α-螺旋构象可以显着减弱铜调节的ROS的产生。
  • 【从Jharia煤层的地层水中分离出的stutzeri假单胞菌诱导了煤产生鼠李糖脂生物表面活性剂。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2012.10.127 复制DOI
    作者列表:Singh DN,Tripathi AK
    BACKGROUND & AIMS: :A strain of Pseudomonas stutzeri was isolated form an enrichment of perchlorate reducing bacteria from the formation water collected from an Indian coalbed which solubilized coal and produced copious amount of biosurfactant when coal was added to the medium. It produced maximum biosurfactant with lignite coal followed by olive oil and soybean oil which was able to emulsify several aromatic hydrocarbons including kerosene oil, diesel oil, hexane, toluene etc. Haemolytic test, growth inhibition of Bacillus subtilis and FTIR analysis showed rhamnolipid nature of the biosurfactant. The stability of the coal induced biosurfactant in pH range of 4-8 and up to 25% NaCl concentration and 100 °C temperature suggests that due to its ability to produce biosurfactant and solubilize coal P. stutzeri may be useful in the coalbed for in situ biotransformation of coal into methane and in the bioremediation of PAHs from oil contaminated sites including marine environments.
    背景与目标: : 从印度煤层收集的地层水中分离出一株stutzeri假单胞菌,富集高氯酸盐还原细菌,当将煤添加到培养基中时,该地层水溶解了煤并产生了大量的生物表面活性剂。它用褐煤和橄榄油和大豆油产生最大的生物表面活性剂,能够乳化几种芳香烃,包括煤油,柴油,己烷,甲苯等。溶血试验,枯草芽孢杆菌的生长抑制和FTIR分析显示了生物表面活性剂的鼠李糖脂性质。煤诱导的生物表面活性剂在4-8的pH范围内以及高达25% 的NaCl浓度和100 °C的温度下的稳定性表明,由于其能够产生生物表面活性剂和溶解煤P. stutzeri可能在煤层中用于将煤原位生物转化为甲烷以及在PAHs的生物修复中石油污染场地,包括海洋环境。
  • 【UPD3细胞因子通过调节干细胞微环境中的JAK/STAT信号来耦合环境挑战和肠道干细胞分裂。】 复制标题 收藏 收藏
    DOI:10.1016/j.ydbio.2012.10.023 复制DOI
    作者列表:Zhou F,Rasmussen A,Lee S,Agaisse H
    BACKGROUND & AIMS: :In Drosophila, the replacement of spent enterocytes (ECs) relies on division of intestinal stem cells (ISCs) and differentiation of their progeny, the enteroblasts (EBs). Recent studies have revealed a role for JAK/STAT signaling in the modulation of the rate of ISC division in response to environmental challenge. Here, we demonstrate the critical role of the UPD3 cytokine in the JAK/STAT-dependent response to enteric infection. We show that upd3 expression is activated in ECs and in EBs that massively differentiate in response to challenge. We show that the UPD3 cytokine, which is secreted basally and accumulates at the basement membrane, is required for stimulation of JAK/STAT signaling in EBs and visceral muscles (VMs). We further show that stimulation of ISC division requires active JAK/STAT signaling in EBs and VMs, but apparently not in ISCs. Our results suggest that EBs and VMs modulate the rate of the EGFR-dependent ISC division through upd3-dependent production of the EGF ligands Spitz and Vein, respectively. This study therefore supports the notion that the production of the UPD3 cytokine in stem cell progeny (ECs and EBs) stimulates intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment (EBs and VMs).
    背景与目标: : 在果蝇中,用过的肠细胞 (ECs) 的替代依赖于肠干细胞 (isc) 的分裂及其后代,肠成细胞 (EBs) 的分化。最近的研究表明,JAK/STAT信号在响应环境挑战的ISC划分速率调节中的作用。在这里,我们证明了UPD3细胞因子在JAK/STAT依赖性肠道感染反应中的关键作用。我们证明了upd3表达在ECs和EBs中被激活,这些响应挑战而发生了巨大分化。我们表明,UPD3细胞因子是基底分泌并积聚在基底膜上的,是刺激EBs和内脏肌肉 (VMs) 中JAK/STAT信号传导所必需的。我们进一步表明,刺激ISC分区需要在EBs和vm中发出主动的JAK/STAT信号,但显然不在ISC中。我们的结果表明,EBs和VMs分别通过upd3-dependent产生EGF配体Spitz和静脉来调节EGFR依赖性ISC分裂的速率。因此,这项研究支持以下观点: 干细胞后代 (ECs和EBs) 中UPD3细胞因子的产生通过调节干细胞微环境 (EBs和VMs) 中的JAK/STAT信号来刺激肠道干细胞分裂。

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