• 【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。
  • 【用于第二代生物燃料生产的宏基因组功能性纤维素酶的生物勘探: 综述。】 复制标题 收藏 收藏
    DOI:10.1080/1040841X.2017.1337713 复制DOI
    作者列表:Tiwari R,Nain L,Labrou NE,Shukla P
    BACKGROUND & AIMS: :Second generation biofuel production has been appeared as a sustainable and alternative energy option. The ultimate aim is the development of an industrially feasible and economic conversion process of lignocellulosic biomass into biofuel molecules. Since, cellulose is the most abundant biopolymer and also represented as the photosynthetically fixed form of carbon, the efficient hydrolysis of cellulose is the most important step towards the development of a sustainable biofuel production process. The enzymatic hydrolysis of cellulose by suites of hydrolytic enzymes underlines the importance of cellulase enzyme system in whole hydrolysis process. However, the selection of the suitable cellulolytic enzymes with enhanced activities remains a challenge for the biorefinery industry to obtain efficient enzymatic hydrolysis of biomass. The present review focuses on deciphering the novel and effective cellulases from different environmental niches by unculturable metagenomic approaches. Furthermore, a comprehensive functional aspect of cellulases is also presented and evaluated by assessing the structural and catalytic properties as well as sequence identities and expression patterns. This review summarizes the recent development in metagenomics based approaches for identifying and exploring novel cellulases which open new avenues for their successful application in biorefineries.
    背景与目标: : 第二代生物燃料生产已成为可持续和替代能源的选择。最终目的是开发一种工业上可行且经济地将木质纤维素生物质转化为生物燃料分子的过程。由于纤维素是最丰富的生物聚合物,也表示为光合固定形式的碳,因此纤维素的有效水解是发展可持续生物燃料生产过程的最重要步骤。通过一系列水解酶对纤维素进行酶促水解,突显了纤维素酶酶系统在整个水解过程中的重要性。然而,选择具有增强活性的合适的纤维素分解酶仍然是生物精炼工业获得生物质有效酶水解的挑战。本综述的重点是通过不可培养的宏基因组方法从不同的环境中破译新颖有效的纤维素酶。此外,还通过评估结构和催化特性以及序列同一性和表达模式来介绍和评估纤维素酶的综合功能方面。这篇综述总结了基于宏基因组学的方法在鉴定和探索新的纤维素酶方面的最新发展,为它们在生物精炼中的成功应用开辟了新的途径。
  • 【BAG-1抑制结直肠肿瘤细胞中关键调节细胞因子转化生长因子 β (TGF-β1) 的表达。】 复制标题 收藏 收藏
    DOI:10.1038/onc.2012.480 复制DOI
    作者列表:Skeen VR,Collard TJ,Southern SL,Greenhough A,Hague A,Townsend PA,Paraskeva C,Williams AC
    BACKGROUND & AIMS: :As colorectal cancer remains the second highest cause of cancer-related deaths in much of the industrialised world, identifying novel strategies to prevent colorectal tumour development remains an important challenge. BAG-1 is a multi-functional protein, the expression of which is up-regulated at relatively early stages in colorectal tumorigenesis. Importantly, BAG-1 is thought to enhance colorectal tumour progression through promoting tumour cell survival. Here, we report for the first time a novel role for BAG-1, establishing it as a suppressor of transforming growth factor β (TGF-β1) expression in colorectal tumour cells. Microarray analysis first highlighted the possibility that BAG-1 may regulate TGF-β1 expression, a key cytokine in normal colonic tissue homoeostasis. Q-RT-PCR and ELISA demonstrated TGFB1 mRNA and protein expression to be significantly increased when BAG1 levels were reduced by small interfering RNA; additionally, induction of BAG-1L caused suppression of TGFB1 mRNA in colorectal tumour cells. Using reporter and chromatin immunoprecipitation assays, a direct association of BAG-1 with the TGFB1 gene regulatory region was identified. Immunohistochemistry and Weiser fraction data indicated that the levels of BAG-1 and TGF-β1 are inversely correlated in the normal colonic epithelium in vivo, consistent with a role for BAG-1-mediated repression of TGF-β1 production. In vitro studies showed that the change in TGF-β1 production following manipulation of BAG-1 is functionally relevant; through induction of anchorage-independent growth in TGF-β1-dependent normal rat kidney fibroblasts and regulation of SMAD2 phosphorylation in TGF-β1-sensitive adenoma cells. Taken together, this study identifies the anti-apoptotic protein BAG-1 as a suppressor of the inhibitory growth factor TGF-β1, suggesting that high expression of BAG-1 can impact on a number of the hallmarks of cancer, of potential importance in promoting the early stages of colorectal tumorigenesis. Establishing BAG-1 as a repressor of TGF-β1 has important biological implications, and highlights a new role for BAG-1 in colorectal tumorigenesis.
    背景与目标: : 由于大肠癌仍然是许多工业化国家中癌症相关死亡的第二大原因,因此确定预防大肠癌发展的新策略仍然是一项重要挑战。BAG-1是一种多功能蛋白,其表达在结直肠肿瘤发生的相对早期阶段上调。重要的是,BAG-1被认为可以通过促进肿瘤细胞存活来促进结直肠肿瘤的进展。在这里,我们首次报道了BAG-1的新作用,将其确立为大肠肿瘤细胞中转化生长因子 β (TGF-β1) 表达的抑制因子。微阵列分析首先强调了BAG-1可能调节TGF-β1表达的可能性,TGF-β1是正常结肠组织平衡中的关键细胞因子。Q-rt-pcr和ELISA证明,当小干扰RNA降低BAG1水平时,TGFB1 mRNA和蛋白表达显着增加; 此外,BAG-1L的诱导引起大肠肿瘤细胞中TGFB1 mRNA的抑制。使用报告基因和染色质免疫沉淀测定法,鉴定了BAG-1与TGFB1基因调控区的直接关联。免疫组织化学和Weiser分数数据表明,体内正常结肠上皮中BAG-1和TGF-β1的水平呈负相关,这与BAG-1介导的TGF-β1产生抑制作用一致。体外研究表明,操纵BAG-1后TGF-β1产生的变化在功能上是相关的; 通过诱导TGF-β1依赖性正常大鼠肾脏成纤维细胞中的锚定依赖性生长以及调节TGF-β1敏感性腺瘤细胞中的SMAD2磷酸化。总之,这项研究确定了抗凋亡蛋白BAG-1作为抑制性生长因子TGF-β1的抑制因子,表明BAG-1的高表达可以影响许多癌症的特征,在促进结直肠肿瘤发生的早期阶段具有潜在的重要性。建立BAG-1作为TGF-β1的阻遏物具有重要的生物学意义,并突出了BAG-1在结直肠肿瘤发生中的新作用。
  • 【中间链球菌中通过血液成分产生中间菌素的阳性和阴性控制途径。】 复制标题 收藏 收藏
    DOI:10.1128/IAI.00379-17 复制DOI
    作者列表:Tomoyasu T,Yamasaki T,Chiba S,Kusaka S,Tabata A,Whiley RA,Nagamune H
    BACKGROUND & AIMS: :Streptococcus intermedius is an opportunistic bacterial pathogen secreting a human-specific cytolysin called intermedilysin (ILY) as a major pathogenic factor. This bacterium can degrade glycans into monosaccharides using two glycosidases, multisubstrate glycosidase A (MsgA) and neuraminidase (NanA). Here, we detected a stronger hemolytic activity mediated by ILY when S. intermedius PC574 was cultured in fetal bovine serum (FBS) than when it was grown in the standard culture medium. FBS-cultured cells also showed higher MsgA and NanA activity, although overproduction of ILY in FBS was undetectable in mutants nanA-null and msgA-null. Addition of purified MsgA and NanA to the FBS resulted in a release of 2.8 mM galactose and 4.3 mM N-acetylneuraminic acid; these sugar concentrations were sufficient to upregulate the expression of ILY, MsgA, and NanA. Conversely, when strain PC574 was cultured in human plasma, no similar increase in hemolytic activity was observed. Moreover, addition of human plasma to the culture in FBS appeared to inhibit the stimulatory effect of FBS on ILY, MsgA, and NanA, although there were individual differences among the plasma samples. We confirmed that human plasma contains immunoglobulins that can neutralize ILY, MsgA, and NanA activities. In addition, human plasma had a neutralizing effect on cytotoxicity of S. intermedius toward HepG2 cells in FBS, and a higher concentration of human plasma was necessary to reduce the cytotoxicity of an ILY-high-producing strain than an ILY-low-producing strain. Overall, our data show that blood contains factors that stimulate and inhibit ILY expression and activity, which may affect pathogenicity of S. intermedius.
    背景与目标: : 中间链球菌是一种机会性细菌病原体,分泌一种称为intermedilysin (ILY) 的人类特异性溶细胞素作为主要致病因子。该细菌可以使用两种糖苷酶,多底物糖苷酶A (MsgA) 和神经氨酸酶 (NanA) 将聚糖降解为单糖。在这里,与在标准培养基中生长时相比,当在胎牛血清 (FBS) 中培养中间S. intermedius PC574时,我们检测到由ILY介导的溶血活性更强。FBS培养的细胞也显示出较高的MsgA和NanA活性,尽管在突变体nanA-null和msgA-null中无法检测到FBS中ILY的过量产生。将纯化的MsgA和NanA添加到FBS中导致释放2.8 mM半乳糖和4.3 mM N-乙酰神经氨酸; 这些糖浓度足以上调ILY,MsgA和NanA的表达。相反,当在人血浆中培养PC574菌株时,未观察到类似的溶血活性增加。此外,尽管血浆样品之间存在个体差异,但将人血浆添加到FBS的培养物中似乎抑制了FBS对ILY,MsgA和NanA的刺激作用。我们证实人血浆中含有免疫球蛋白,可以中和ILY,MsgA和NanA活性。此外,人血浆对FBS中中间S. intermedius对HepG2细胞的细胞毒性具有中和作用,并且需要更高浓度的人血浆来降低ILY高产菌株的细胞毒性比ILY低产菌株的细胞毒性。总体而言,我们的数据表明,血液中含有刺激和抑制ILY表达和活性的因子,这可能会影响中间S. intermedius的致病性。
  • 【通过用细胞表面工程酵母菌株减轻纤维素酶的不可逆吸附,同时改善了结晶纤维素的糖化和乙醇生产。】 复制标题 收藏 收藏
    DOI:10.1007/s00253-012-4587-x 复制DOI
    作者列表:Matano Y,Hasunuma T,Kondo A
    BACKGROUND & AIMS: :Enzymatic hydrolysis of cellulosic material is an essential step in the bioethanol production process. However, complete cellulose hydrolysis by cellulase is difficult due to the irreversible adsorption of cellulase onto cellulose. Thus, part of the cellulose remains in crystalline form after hydrolysis. In this study, after 96-h hydrolysis of Avicel crystalline cellulose, 47.1 % of the cellulase was adsorbed on the cellulose surface with 10.8 % crystalline cellulose remaining. In simultaneous saccharification and fermentation of 100 g/L Avicel with 1.0 filter paper unit/mL cellulase, a wild-type yeast strain produced 44.7 g/L ethanol after 96 h. The yield of ethanol was 79.7 % of the theoretical yield. On the other hand, a recombinant yeast strain displaying various cellulases, such as β-glucosidase, cellobiohydrolase, and endoglucanase, produced 48.9 g/L ethanol, which corresponds to 87.3 % of the theoretical yield. Higher ethanol production appears to be attributable to higher efficiency of cellulase displayed on the cell surface. These results suggest that cellulases displayed on the yeast cell surface improve hydrolysis of Avicel crystalline cellulose. Indeed, after the 96-h simultaneous saccharification and fermentation using the cellulase-displaying yeast, the amount of residual cellulose was 1.5 g/L, one quarter of the cellulose remaining using the wild-type strain, a result of the alleviation of irreversible adsorption of cellulases on the crystalline cellulose.
    背景与目标: : 纤维素材料的酶水解是生物乙醇生产过程中必不可少的步骤。然而,由于纤维素酶不可逆地吸附在纤维素上,纤维素酶很难完全水解纤维素。因此,部分纤维素在水解后保持结晶形式。在这项研究中,在Avicel结晶纤维素水解96小时后,纤维素酶的47.1% 吸附在纤维素表面,剩余10.8% 结晶纤维素。在用1.0滤纸单位/mL纤维素酶同时糖化和发酵100g/L Avicel的过程中,野生型酵母菌株在96小时后产生44.7g/L乙醇。乙醇的产率是理论产率的79.7%。另一方面,显示各种纤维素酶 (例如 β-葡萄糖苷酶、纤维二糖水解酶和内切葡聚糖酶) 的重组酵母菌株产生48.9g/L乙醇,这相当于理论产量的87.3%。较高的乙醇产量似乎归因于细胞表面显示的纤维素酶效率较高。这些结果表明,酵母细胞表面显示的纤维素酶可改善Avicel结晶纤维素的水解。实际上,在使用显示纤维素酶的酵母进行96小时的同时糖化和发酵之后,残留纤维素的量为1.5g/L,为使用野生型菌株剩余纤维素的四分之一,这是纤维素酶在结晶纤维素上不可逆吸附的减轻的结果。
  • 【在空运生物反应器中大规模培养紫锥菊不定根,用于生产菊科酸,绿原酸和茶多酸。】 复制标题 收藏 收藏
    DOI:10.1007/s10529-007-9399-1 复制DOI
    作者列表:Wu CH,Murthy HN,Hahn EJ,Paek KY
    BACKGROUND & AIMS: :Adventitious roots of Echinacea purpurea were cultured in airlift bioreactors (20 l, 500 l balloon-type, bubble bioreactors and 1,000 l drum-type bubble bioreactor) using Murashige and Skoog (MS) medium with 2 mg indole butyric acid l(-1) and 50 g sucrose l(-1) for the production of chichoric acid, chlorogenic acid and caftaric acid. In the 20 l bioreactor (containing 14 l MS medium) a maximum yield of 11 g dry biomass l(-1) was achieved after 60 days. However, the amount of total phenolics (57 mg g(-1) DW), flavonoids (34 mg g(-1) DW) and caffeic acid derivatives (38 mg g(-1) DW) were highest after 50 days. Based on these studies, pilot-scale cultures were established and 3.6 kg and 5.1 kg dry biomass were achieved in the 500 l and 1,000 l bioreactors, respectively. The accumulation of 5 mg chlorogenic acid g(-1) DW, 22 mg chichoric acid g(-1) DW and 4 mg caftaric acids g(-1) DW were achieved with adventitious roots grown in 1,000 l bioreactors.
    背景与目标: : 紫锥菊不定根在气举生物反应器 (20 l,500 l球囊型,气泡生物反应器和1,000 l鼓式气泡生物反应器),使用具有2 mg吲哚丁酸l(-1) 和50 g蔗糖l(-1) 的Murashige和Skoog (MS) 培养基来生产菊苣酸、绿原酸和茶多酸。在20 l生物反应器 (包含14 l MS培养基) 中,60天后最大产量为11g干生物质l(-1)。然而,50天后总酚 (57 mg g(-1) DW),类黄酮 (34 mg g(-1) DW) 和咖啡酸衍生物 (38 mg g(-1) DW) 的含量最高。基于这些研究,建立了中试规模的培养物,并分别在500 l和1,000 l生物反应器中实现了3.6千克和5.1千克干生物质。通过在1,000 l生物反应器中生长的不定根,实现了5 mg绿原酸g(-1) DW,22 mg菊科酸g(-1) DW和4 mg咖啡酸g(-1) DW的积累。

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