• 【白藜芦醇通过阻断β细胞的K(ATP)和K(V)通道增强胰岛素分泌。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2007.04.062 复制DOI
    作者列表:Chen WP,Chi TC,Chuang LM,Su MJ
    BACKGROUND & AIMS: :The present study investigated the effect of resveratrol on the electrophysiology and insulin secretion of pancreatic beta cells, and examined resveratrol-induced alterations in insulin levels and plasma glucose of normal and streptozotocin-induced diabetic rats. Whole-cell voltage clamp study in the MIN6 cell, a mouse beta cell line, revealed that resveratrol significantly inhibited ATP-sensitive K(+) current at 3 micromol/l, and voltage-gated K(+) currents at 30 micromol/l. Ca(2+)-activated K(+) current was activated by resveratrol at 100 micromol/l. In MIN6 cells stained with membrane potential dye DiBAC(4)(5), resveratrol markedly depolarized membrane potential at the concentrations of 3-100 micromol/l. Insulin secretion was increased in the presence of resveratrol in MIN6, Hit-T15, and RIN-m5F cells. Resveratrol (3 mg/kg, i.p.) increased insulin secretion associated with a lowering in plasma glucose in normal rats, but not in streptozotocin-diabetic rats within the initial 60 min. In conclusion, resveratrol can act as an insulin-secretagogue through I(KATP) and I(KV) inhibition which can contribute to plasma glucose lowering effect in normal rats.
    背景与目标: :本研究调查了白藜芦醇对胰腺β细胞电生理和胰岛素分泌的影响,并研究了白藜芦醇诱导的正常和链脲佐菌素诱导的糖尿病大鼠胰岛素水平和血浆葡萄糖的变化。在MIN6细胞(一种小鼠​​β细胞系)中进行全细胞电压钳研究,发现白藜芦醇在3微摩尔/升时显着抑制ATP敏感的K()电流,在30微摩尔/升时抑制电压门控的K()电流。 Ca(2)激活的K()电流被白藜芦醇以100 micromol / l激活。在用膜电位染料DiBAC(4)(5)染色的MIN6细胞中,白藜芦醇在3-100 micromol / l的浓度下可显着去极化膜电位。在MIN6,Hit-T15和RIN-m5F细胞中存在白藜芦醇时,胰岛素分泌增加。在正常大鼠中,白藜芦醇(3 mg / kg,i.p.)在最初60分钟内胰岛素分泌增加与血浆葡萄糖降低有关,但在链脲佐菌素-糖尿病大鼠中却没有。总之,白藜芦醇可以通过I(KATP)和I(KV)抑制作用起胰岛素分泌的作用,这可以促进正常大鼠血浆葡萄糖的降低作用。
  • 【妊娠期唾液皮质醇分泌的模式及其对评估方案的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biopsycho.2006.07.005 复制DOI
    作者列表:Harville EW,Savitz DA,Dole N,Herring AH,Thorp JM,Light KC
    BACKGROUND & AIMS: :Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.
    背景与目标: :Cortisol在研究中用作心理压力的生物标记。物流方面的考虑认为应收集尽可能少的样本,并与昼夜节律和个体内部差异保持平衡。 100名孕妇在清醒,醒后30分钟和上午11:00,下午5:00和下午9:00每天提供五份唾液样本,为期3天。监控人员确认了收集时间。在诊所就诊时采集了另一个样本。使用15个度量作为金标准,将相关性和曲线下的平均面积(AUC)与子集和单个临床样本进行比较,以评估备用收集方案。 1天中的五个样本或涉及早晨和晚上样本的协议与平均AUC的相关性最高(相关系数范围从0.82到0.88)。将临床测量标准化为一天中的某个时间并不能显着改善与平均AUC的相关性。与报告的压力测量值的相关性也不强。
  • 【本文中的内容:霍勒斯·达文波特(Horace Davenport),碳酸酐酶和胃酸分泌。】 复制标题 收藏 收藏
    DOI:10.1152/advan.00083.2006 复制DOI
    作者列表:Rangachari PK
    BACKGROUND & AIMS: :Many standard textbooks of physiology have a diagram that shows the transporting elements that lead to the secretion of HCl by the parietal cell. The transporters are neatly aligned, and students see an elegant mechanism that neatly balances the ions to maintain electroneutrality. They little realize the time and effort required to tease out each of those steps bit by bit. This essay uses three papers by Horace Davenport to highlight the experimental evidence for a crucial step in that process: the generation of H(+) and HCO(3)(-) through the agency of carbonic anhydrase. All three papers form part of the classic papers available through the American Physiological Society Legacy Project.
    背景与目标: :许多生理学标准教科书都有一张图表,显示了导致顶细胞分泌HCl的转运元素。转运蛋白排列整齐,学生们看到了一种优雅的机制,它可以平衡离子以保持电子中性。他们几乎没有一点一点地花时间来梳理每个步骤所需要的时间和精力。本文使用Horace Davenport的三篇论文来强调该过程中关键步骤的实验证据:通过碳酸酐酶的作用生成H()和HCO(3)(-)。所有这三篇论文都是可通过美国生理学会旧版计划获得的经典论文的一部分。
  • 【暴露于颗粒物2.5(PM2.5)会诱导巨噬细胞依赖性炎症,其特征是Th1 / Th17细胞因子分泌增加和细胞毒性增加。】 复制标题 收藏 收藏
    DOI:10.1016/j.intimp.2017.06.019 复制DOI
    作者列表:Ma QY,Huang DY,Zhang HJ,Wang S,Chen XF
    BACKGROUND & AIMS: :Particulate matter PM2.5 is a class of airborne particles and droplets with sustained high levels in many developing countries. Epidemiological studies have shown the association between sustained high level of PM2.5 and the risk of many diseases in the respiratory system, including lung cancer. However, the precise mechanisms through which PM2.5 induces respiratory diseases are still unclear. In this study, we demonstrated that CD4+ and CD8+ T cells following PM2.5 treatment demonstrated significantly elevated mRNA and protein levels of interferon (IFN)-γ, interleukin (IL)-10, IL-17, and IL-21 production. This increase in cytokines required the presence of macrophages, such that CD4+ and CD8+ T cells treated with PM2.5 in the absence of macrophages did not present higher IFN-γ, IL-10, or IL-21 expression. In contrast, PM2.5-treated macrophages could significantly upregulate T cell cytokine secretion, even when excess PM2.5 was removed from cell culture. We also observed a macrophage-dependent upregulation of granzyme A and granzyme B expression by CD4+ and CD8+ T cells following PM2.5 treatment. These PM2.5-stimulated CD4+ and CD8+ T cells potently induced the death of human bronchial epithelial (HBE) cells. Interestingly, the CD4+ and CD8+ T cells presented synergistic effects at inducing HBE cytotoxicity, such that CD4+ T cells and CD8+ T cells combined resulted in higher HBE cell death than the sum of the separate effects of CD4+ T cells and CD8+ T cells. While blocking cytotoxic molecule release significantly compromised the T cell-mediated cytotoxicity against HBE cells, blocking IFN-γ, but not IL-10, could also slightly but significantly reduce T cell-mediated cytotoxicity. Together, these data demonstrated that PM2.5 could promote the inflammation of cytotoxicity of T cells in a macrophage-dependent manner. In addition, PM2.5-treated macrophages presented long-lasting proinflammatory effects on T cells.
    背景与目标: :颗粒物PM2.5是一类在许多发展中国家持续高水平飞行的空气颗粒和小滴。流行病学研究表明,持续高水平的PM2.5与呼吸系统多种疾病(包括肺癌)的风险之间存在关联。然而,PM2.5诱发呼吸系统疾病的确切机制仍不清楚。在这项研究中,我们证明了PM2.5处理后的CD4和CD8 T细胞显示出干扰素(IFN)-γ,白介素(IL)-10,IL-17和IL-21产生的mRNA和蛋白质水平显着升高。细胞因子的这种增加需要巨噬细胞的存在,以致在没有巨噬细胞的情况下用PM2.5处理的CD4和CD8 T细胞不会表现出更高的IFN-γ,IL-10或IL-21表达。相反,即使从细胞培养物中去除了过量的PM2.5,经PM2.5处理的巨噬细胞也可以显着上调T细胞细胞因子的分泌。我们还观察到PM2.5处理后CD4和CD8 T细胞巨噬细胞依赖颗粒酶A和颗粒酶B表达的上调。这些PM2.5刺激的CD4和CD8 T细胞有效诱导人支气管上皮(HBE)细胞死亡。有趣的是,CD4和CD8 T细胞在诱导HBE细胞毒性方面表现出协同作用,因此与CD4 T细胞和CD8 T细胞单独作用的总和相比,CD4 T细胞和CD8 T细胞的结合导致更高的HBE细胞死亡。尽管阻断细胞毒性分子的释放显着损害了针对HBE细胞的T细胞介导的细胞毒性,但阻断IFN-γ(而非IL-10)也可以略微但显着降低T细胞介导的细胞毒性。总之,这些数据表明PM2.5可以以巨噬细胞依赖性方式促进T细胞的细胞毒性炎症。此外,经PM2.5处理的巨噬细胞对T细胞具有持久的促炎作用。
  • 【甲状腺功能亢进大鼠的胰岛素分泌和作用。】 复制标题 收藏 收藏
    DOI:10.1055/s-2007-1013553 复制DOI
    作者列表:Varnum B,Davidson MB,Venkatesan N
    BACKGROUND & AIMS: :To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.
    背景与目标: :为了深入了解甲状腺毒症中碳水化合物代谢改变的机理,对甲亢大鼠(0.1 mg / kg T4 X 5天)进行了静脉葡萄糖耐量试验(IVGTT)和胰腺抑制试验(PST),以评估胰岛素的分泌和作用体内。甲状腺激素注射显着提高了T4水平(182.8 nM /-11.6(SEM)对50.2 /-6.4; P小于0.001)和基线葡萄糖浓度(9.3 mM /-0.2对7.1 /-0.2; P小于0.001)。体重,基础胰岛素浓度,IVGTT期间的葡萄糖浓度,葡萄糖消失率和稳态血浆葡萄糖水平(SSPG)正常。葡萄糖耐量试验期间和PST期间的胰岛素浓度显着降低。在甲状腺功能亢进的大鼠中,胰岛素的代谢清除率(ml / min / kg /-SEM)显着提高(P小于0.01)(54.4 /-3.5对41.6 /-2.3)。如果从两次测试中获得的葡萄糖浓度中减去不同的基线葡萄糖值,则注射T4的动物的葡萄糖消失率和SSPG水平的下降均显着增强。因此,在甲状腺功能亢进的大鼠中,胰岛素分泌减少,胰岛素清除率增加,胰岛素敏感性正常或可能增强。
  • 【从东方红腹蟾蜍Bombina Orientalis的皮肤分泌物中发现两种具有抗菌和抗癌活性的Bombinin肽。】 复制标题 收藏 收藏
    DOI:10.1111/cbdd.13055 复制DOI
    作者列表:Zhou C,Wang Z,Peng X,Liu Y,Lin Y,Zhang Z,Qiu Y,Jin M,Wang R,Kong D
    BACKGROUND & AIMS: :Amphibian skin secretions are known to contain numerous peptides with a large array of biological activities. Bombinins are a group of amphibian-derived peptides with broad spectrum antimicrobial activities that have been only identified from the ancient toad species, Bombina. In this study, we described the identification and characterization of a novel bombinin precursor which encoded a bombinin-like peptide (BLP-7) and a novel bombinin H-type peptide (named as Bombinin H-BO) from the skin secretion of Oriental fire-bellied toad, Bombina orientalis. The primary structures of both mature peptides were determined by combinations of molecular cloning of peptide precursor-encoding cDNAs and mass spectrometry techniques. Secondary structure prediction revealed that both peptides had cationic amphipathic α-helical structural features. The synthetic replicate of BLP-7 displayed more potent antimicrobial activity than Bombinin H-BO against Gram-positive and Gram-negative bacteria and yeast. Also, in vitro antitumour assay showed that both peptides possessed obvious antiproliferative activity on three human hepatoma cells (Hep G2/SK-HEP-1/Huh7) at the non-toxic doses. These results indicate the peptide family of bombinins could be a potential source of drug candidates for anti-infection and anticancer therapy.
    背景与目标: 已知两栖动物的皮肤分泌物中含有许多具有多种生物活性的肽。 Bombinins是一组具有广谱抗菌活性的两栖动物衍生肽,仅从古老的蟾蜍物种Bombina中鉴定出来。在这项研究中,我们描述了一种从东方火的皮肤分泌物中鉴定出一种新的蛙新蛋白前体的鉴定和表征,该前体编码了一种蛙新蛋白样肽(BLP-7)和一种新颖的蛙新蛋白H型肽(称为蛙新蛋白H-BO)。腹蟾蜍,Bombina Orientalis。通过结合肽前体编码cDNA的分子克隆和质谱技术确定两种成熟肽的一级结构。二级结构预测表明,两种肽均具有阳离子两亲性α-螺旋结构特征。与Bombinin H-BO相比,BLP-7的合成复制品对革兰氏阳性和革兰氏阴性细菌和酵母菌显示出更强的抗菌活性。同样,体外抗肿瘤试验表明,两种肽均以无毒剂量对三种人肝癌细胞(Hep G2 / SK-HEP-1 / Huh7)具有明显的抗增殖活性。这些结果表明,蛙皮素的肽家族可能是抗感染和抗癌治疗候选药物的潜在来源。
  • 【心脏手术前我们应该抑制胃酸分泌吗?】 复制标题 收藏 收藏
    DOI:10.1213/00000539-199002000-00010 复制DOI
    作者列表:Lehot JJ,Deleat-Besson R,Bastien O,Brun Y,Adeleine P,Robin J,Estanove S
    BACKGROUND & AIMS: :Stress can decrease intragastric pH and cause erosion of gastric mucosa. Because cardiac surgery and cardiopulmonary bypass represent a major stress, the effects on intragastric pH of an H2-receptor antagonist, ranitidine, and an M1-muscarinic antagonist, pirenzepine, were evaluated. Intragastric pH was measured throughout elective cardiac surgery in 60 patients by a digital pH-meter during fentanyl-diazepam-nitrous oxide (50%) anesthesia. The gastric content was sampled at closure of the chest for bacterial count. Oral preoperative medication given randomly included (n = 20 in each group) 0.3 mg/kg diazepam 1 h before induction (group 1); diazepam plus ranitidine (150 mg) 1 h before induction (group 2); and diazepam plus pirenzepine (50 mg) on the evening before surgery and 1 h before induction of anesthesia (group 3). At induction intragastric pH was higher in group 2 (mean +/- SD = 7.42 +/- 1.07) than in group 1 (5.28 +/- 2.14) (P less than 0.01) but was not significantly different in group 3 (5.78 +/- 1.89) than in group 1. In no group did intragastric pH change significantly during surgery. Gastric juice was sterile in 92% of group 1, in 25% of group 2, and in 71% of group 3 patients (P less than 0.01). Postoperatively no gastrointestinal complications occurred, but there was a trend toward more patients developing nosocomial pneumonias in groups 2 and 3 (15%) than in group 1 (0%) (P = 0.06). Intraoperative intragastric pH is relatively high after diazepam premedication, thus the preoperative addition of ranitidine or pirenzepine would not be necessary and may possibly be hazardous.
    背景与目标: :压力可降低胃内pH值并引起胃粘膜糜烂。因为心脏手术和体外循环是主要的压力,所以评估了H2受体拮抗剂雷尼替丁和M1毒蕈碱拮抗剂哌仑西平对胃内pH的影响。在芬太尼-地西p-一氧化二氮(50%)麻醉期间,通过数字式pH计在整个择期心脏手术中对60例患者的胃内pH进行了测量。在胸部闭合时取样胃内容物以进行细菌计数。诱导前1小时随机给予口服术前药物(每组20例)0.3 mg / kg地西epa(第1组);诱导前1小时地西epa加雷尼替丁(150 mg)(第2组);在手术前的晚上和麻醉诱导前的1小时(第3组)和地西epa加哌仑西平(50 mg)。诱导时,第2组的胃内pH高于第1组(平均SD = 7.42 /-1.07)(第5.28 /-2.14)(P小于0.01),但第3组无明显差异(5.78 /-1.89)。与第1组相比。在手术期间,没有任何组的胃内pH发生显着变化。第1组的92%,第2组的25%和第3组的71%的患者的胃液是无菌的(P小于0.01)。术后未发生胃肠道并发症,但第2组和第3组(15%)比第1组(0%)有更多的患者发生医院内肺炎(P = 0.06)。地西epa预处理后,术中胃内pH值相对较高,因此术前不必添加雷尼替丁或哌仑西平,可能会很危险。
  • 【烯丙基硫醇和各种洋葱来源的化合物对Hep-G2细胞胆固醇合成和分泌的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0742-8413(00)00106-7 复制DOI
    作者列表:Cho BH,Xu S
    BACKGROUND & AIMS: :The present study was undertaken to compare the effects of allyl mercaptan (AM), a major metabolite of garlic, with several garlic constituents and extracts on cytotoxicity, cholesterol synthesis and its secretion in Hep-G2 cells. The cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), and treated with 5, 25, 50, 125, 250 and 500 microg/ml of AM, diallyl disulfide (DD), diallyl trisulfide (DT), steam-distilled garlic oil (SD) or vinyl-dithiin oil of garlic (VD) for 4 h. At concentrations up to 50 microg/ml, no significant cytotoxic effect was found in any group, but at concentrations above 250 microg/ml, the cell viability decreased drastically in all groups compared to the control. The treatment of cells with 25 microg/ml (non-cytotoxic concentration) of AM, DD, DT, SD for 4 h significantly inhibited [3H]acetate incorporation into cholesterol compared to that of the control (P < 0.05). The secretion of cholesterol into the medium was also significantly decreased in all groups except for VD. The treatment of cells with those allium constituents had no effect on either [3H]acetate incorporation into fatty acids or [3H]glycerol incorporation into triglyceride or phospholipid.
    背景与目标: :本研究旨在比较大蒜的主要代谢产物烯丙基硫醇(AM)与几种大蒜成分和提取物对Hep-G2细胞的细胞毒性,胆固醇合成及其分泌的影响。细胞在补充有10%胎牛血清(FBS)的Dulbecco改良Eagle培养基(DMEM)中生长,并用5、25、50、125、250和500 microg / ml AM,二烯丙基二硫化物(DD),二烯丙基处理将三硫化物(DT),蒸汽蒸馏的大蒜油(SD)或大蒜的乙烯基二硫精油(VD)搅拌4小时。在最高浓度为50微克/毫升的情况下,任何组均未发现明显的细胞毒性作用,但在浓度高于250微克/毫升的情况下,与对照组相比,所有组的细胞活力均急剧下降。与对照组相比,用25 microg / ml(无细胞毒性浓度)的AM,DD,DT,SD处理细胞4小时可显着抑制[3H]乙酸盐掺入胆固醇。除VD外,所有组中胆固醇向培养基中的分泌也显着减少。用那些葱属成分处理细胞对[3H]乙酸酯掺入脂肪酸或[3H]甘油掺入甘油三酸酯或磷脂均无影响。
  • 【放线放线杆菌放线杆菌分泌RTX白毒素。】 复制标题 收藏 收藏
    DOI:10.1128/iai.68.11.6094-6100.2000 复制DOI
    作者列表:Kachlany SC,Fine DH,Figurski DH
    BACKGROUND & AIMS: :Actinobacillus actinomycetemcomitans, the etiologic agent for localized juvenile periodontitis and certain other human infections, such as endocarditis, expresses a leukotoxin that acts on polymorphonuclear leukocytes and macrophages. Leukotoxin is a member of the highly conserved repeat toxin (RTX) family of bacterial toxins expressed by a variety of pathogenic bacteria. While the RTX toxins of other bacterial species are secreted, the leukotoxin of A. actinomycetemcomitans is thought to remain associated with the bacterial cell. We have examined leukotoxin production and localization in rough (adherent) and smooth (nonadherent) strains of A. actinomycetemcomitans. We found that leukotoxin expressed by the rough, adherent, clinical isolate CU1000N is indeed cell associated, as expected. However, we were surprised to find that smooth, nonadherent strains of A. actinomycetemcomitans, including Y4, JP2 (a strain expressing a high level of toxin), and CU1060N (an isogenic smooth variant of CU1000N), secrete an abundance of leukotoxin into the culture supernatants during early stages of growth. After longer times of incubation, leukotoxin disappears from the supernatants, and its loss is accompanied by the appearance of a number of low-molecular-weight polypeptides. The secreted leukotoxin is active, as evidenced by its ability to kill HL-60 cells in vitro. We found that the growth phase and initial pH of the growth medium significantly affect the abundance of secreted leukotoxin, and we have developed a rapid (<2 h) method to partially purify large amounts of leukotoxin. Remarkably, mutations in the tad genes, which are required for tight nonspecific adherence of A. actinomycetemcomitans to surfaces, cause leukotoxin to be released from the bacterial cell. These studies show that A. actinomycetemcomitans has the potential to secrete abundant leukotoxin. It is therefore appropriate to consider a possible role for leukotoxin secretion in the pathogenesis of A. actinomycetemcomitans.
    背景与目标: 放线杆菌放线杆菌(Actinobacillus actinomycetemcomitans)是局部性青少年牙周炎和某些其他人类感染(如心内膜炎)的病原体,其表达的白细胞毒素作用于多形核白细胞和巨噬细胞。白细胞毒素是多种致病细菌表达的细菌毒素的高度保守重复毒素(RTX)家族的成员。虽然其他细菌物种的RTX毒素被分泌出来,但认为放线放线杆菌的白细胞毒素仍与细菌细胞结合。我们已经检查了粗毒素(粘附)和光滑(非粘附)菌株放线放线杆菌中白细胞毒素的产生和定位。我们发现,如预期的那样,由粗糙的,粘附的临床分离株CU1000N表达的白细胞毒素确实与细胞相关。但是,我们惊讶地发现光滑的,非粘附性的放线放线杆菌菌株,包括Y4,JP2(表达高水平毒素的菌株)和CU1060N(CU1000N的同基因光滑变体),向其中分泌了大量白细胞毒素。在生长的早期培养上清液。经过较长时间的培养,白细胞毒素从上清液中消失,其丢失伴随着许多低分子量多肽的出现。分泌的白细胞毒素具有活性,其体外杀伤HL-60细胞的能力证明了这一点。我们发现,生长培养基的生长期和初始pH值会显着影响分泌的白细胞毒素的丰度,因此,我们开发了一种快速(<2小时)方法来部分纯化大量白细胞毒素。值得注意的是,tad基因中的突变是放线放线杆菌紧密粘附于表面所需的突变,导致白细胞毒素从细菌细胞中释放出来。这些研究表明,放线放线杆菌有可能分泌丰富的白细胞毒素。因此,有必要考虑白细胞毒素分泌在放线放线杆菌的发病机理中的可能作用。
  • 【作为分子注射器,在大肠杆菌K-12菌株中功能副溶血弧菌III型分泌系统1的功能性克隆。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbrc.2012.09.018 复制DOI
    作者列表:Akeda Y,Kimura T,Yamasaki A,Kodama T,Iida T,Honda T,Oishi K
    BACKGROUND & AIMS: :The type III secretion system (T3SS) of gram-negative bacteria involves dedicated protein translocation machinery that directly injects proteins into target cells. Pathogenic bacteria already benefit from this unique system. The successful functional cloning of this useful tool into non-pathogenic bacteria would help establish novel clinical and basic biotechnology strategies in areas such as vaccine administration, the development of screening systems for anti-T3SS drugs and the target-specific delivery of bioactive compounds. In this study, we successfully cloned the Vibrio parahaemolyticus T3SS1 genetic locus into a non-pathogenic Escherichia coli K-12 strain. Assays performed here revealed that the T3SS1 cloned into the E. coli K-12 strain has the ability to translocate V. parahaemolyticus T3SS1 secreted proteins. Importantly, we also observed this system to allow the E. coli K-12 strain to inject foreign protein, as well as the V. parahaemolyticus T3SS effector, into cultured cells. These results demonstrate a prospective useful tool with experimental and therapeutic applications.
    背景与目标: :革兰氏阴性细菌的III型分泌系统(T3SS)涉及专用的蛋白质转运机制,可直接将蛋白质注射到靶细胞中。致病细菌已经从这种独特的系统中受益。将该有用工具成功地功能克隆到非致病性细菌中,将有助于在疫苗管理,抗T3SS药物筛选系统的开发以及生物活性化合物的靶标特异性递送等领域建立新颖的临床和基础生物技术策略。在这项研究中,我们成功地将副溶血弧菌T3SS1遗传基因座克隆到了非致病性大肠杆菌K-12菌株中。此处进行的分析表明,克隆到大肠杆菌K-12菌株中的T3SS1具有转移副溶血弧菌T3SS1分泌蛋白的能力。重要的是,我们还观察到该系统允许大肠杆菌K-12菌株向培养的细胞中注入外源蛋白以及副溶血弧菌T3SS效应子。这些结果证明了具有实验和治疗应用前景的有用工具。
  • 【母羊LH的搏动性分泌和潮涌性分泌均激活了KNDy(kisspeptin /神经激肽B /强啡肽)神经元。】 复制标题 收藏 收藏
    DOI:10.1210/en.2012-1357 复制DOI
    作者列表:Merkley CM,Porter KL,Coolen LM,Hileman SM,Billings HJ,Drews S,Goodman RL,Lehman MN
    BACKGROUND & AIMS: :KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) appear to mediate the negative feedback actions of estradiol and are thought to be key regulators of pulsatile LH secretion. In the ewe, KNDy neurons may also be involved with the positive feedback actions of estradiol (E(2)) to induce the LH surge, but the role of kisspeptin neurons in the preoptic area (POA) remains unclear. The goal of this study was to identify which population(s) of kisspeptin neurons is (are) activated during the LH surge and in response to the removal of E(2)-negative feedback, using Fos as an index of neuronal activation. Dual-label immunocytochemistry for kisspeptin and Fos was performed on sections containing the ARC and POA from ewes during the luteal phase of the estrous cycle, or before or after the onset of the LH surge (experiment 1), and from ovary-intact, short-term (24 h) and long-term (>30 d) ovariectomized (OVX) ewes in anestrus (experiment 2). The percentage of kisspeptin neurons expressing Fos in both the ARC and POA was significantly higher during the LH surge. In contrast, the percentage of kisspeptin/Fos colocalization was significantly increased in the ARC, but not POA, after both short- and long-term E(2) withdrawal. Thus, POA kisspeptin neurons in the sheep are activated during, and appear to contribute to, E(2)-positive feedback, whereas ARC kisspeptin (KNDy) neurons are activated during both surge and pulsatile modes of secretion and likely play a role in mediating both positive and negative feedback actions of E(2) on GnRH secretion in the ewe.
    背景与目标: 弓形核(ARC)的:KNDy(kisspeptin /神经激肽B / dynorphin)神经元似乎介导雌二醇的负反馈作用,被认为是脉动性LH分泌的关键调节因子。在母羊中,KNDy神经元也可能参与了雌二醇的正反馈作用(E(2))以诱导LH激增,但尚不清楚视蛋白在视前区(POA)中的作用。这项研究的目的是使用Fos作为神经元激活的指标,确定在LH激增过程中激活了哪些基肽素神经元群体,并响应于去除E(2)负反馈而被激活。在发情周期的黄体期,LH激增发作之前或之后(实验1)以及卵巢完整,短时,对包含ARC和POA的母羊切片进行kisseptin和Fos的双标记免疫细胞化学分析期(24小时)和长期(> 30 d)卵巢切除卵巢(OVX)母羊(实验2)。在LH激增期间,在ARC和POA中表达Fos的Kisspeptin神经元的百分比显着较高。相反,在短期和长期撤出E(2)后,ARC中kisepteptin / Fos共定位的百分比显着增加,但POA没有显着增加。因此,绵羊中的POA Kisspeptin神经元在E(2)阳性反馈过程中被激活,并且似乎有助于E(2)阳性反馈,而ARC Kisspeptin(KNDy)神经元在激增和搏动性分泌模式下均被激活,并且可能在介导中发挥作用E(2)对母羊GnRH分泌的正反馈和负反馈作用。
  • 【洛哌丁胺在人体内对胰胆管分泌的抑制作用。】 复制标题 收藏 收藏
    DOI:10.1002/hep.510260201 复制DOI
    作者列表:Thimister PW,Hopman WP,van Roermund RF,Willems HL,Rosenbusch G,Woestenborghs R,Jansen JB
    BACKGROUND & AIMS: Loperamide, a peripherally acting opiate receptor agonist with antidiarrheal action, inhibits ileal and colonic motor function. It was determined whether loperamide also affects gallbladder emptying and pancreatic enzyme secretion in humans. Plasma cholecystokinin (radioimmunoassay), gallbladder volume (ultrasonography), and intraduodenal bilirubin and amylase output (spot sampling) were measured at regular intervals before and during intraduodenal perfusion of an amino acid meal in 8 healthy subjectsonce without and once with pretreatment of 8 mg loperamide, ingested 13 and 4 hours before the start of the meal. Loperamide decreased basal amylase output from 3.2 +/- 0.5 to 1.0 +/- 0.5 kU/h (P < .005) and abolished basal bilirubin output (21 +/- 5 vs. 0 +/- 0 micromol/h; P < .005) into the duodenum. Loperamide increased basal gallbladder volume from 28 +/- 4 to 39 +/- 4 mL (P < .0001) but was without effect on basal plasma cholecystokinin (2.7 +/- 0.3 vs. 3.0 +/- 0.3 pmol/L). During the amino acid meal, pretreatment with loperamide inhibited amylase output from 5.1 +/- 0.8 to 1.6 +/- 0.4 kU/h (P < .001), bilirubin output from 39 +/- 6 to 18 +/- 6 micromol/h (P < .0005) and gallbladder contraction from 47% +/- 3% to 26% +/- 6% (P < .05), whereas loperamide enhanced amino acid-stimulated plasma cholecystokinin from 4.5 +/- 1.6 to 7.6 +/- 1.0 pmol/L (P < .05). It is concluded that loperamide inhibits basal and amino acid-stimulated gallbladder motility and intraduodenal output of bilirubin and amylase, despite an enhanced postprandial cholecystokinin release.

    背景与目标: Loperamide是一种具有抗腹泻作用的外周作用阿片受体激动剂,可抑制回肠和结肠运动功能。已确定洛哌丁胺是否还会影响人的胆囊排空和胰腺酶的分泌。在8位健康受试者中,在未进行或未进行8 mg洛哌丁胺预处理的情况下,定期对十二指肠内进行氨基酸餐前和期间进行血浆胆囊收缩素(放射免疫分析),胆囊体积(超声检查),十二指肠内胆红素和淀粉酶输出量(现场取样)的测量。 ,在用餐开始前13和4小时摄入。洛哌丁胺将基础淀粉酶的输出量从3.2 /-0.5降低至1.0 /-0.5 kU / h(P <.005),并废除了基础胆红素输出量(21 /-5 vs. 0 /-0 micromol / h; P <.005)十二指肠。洛哌丁胺将基础胆囊体积从28 /-4增加到39 /-4 mL(P <.0001),但对基础血浆胆囊收缩素没有影响(2.7 /-0.3对3.0 /-0.3 pmol / L)。在氨基酸餐期间,用洛哌丁胺预处理可将淀粉酶的输出量从5.1 /-0.8降低到1.6 /-0.4 kU / h(P <.001),将胆红素的输出量从39 /-6抑制到18 /-6 micromol / h(P < .0005)和胆囊收缩从47%/-3%增至26%/-6%(P <.05),而洛哌丁胺将氨基酸刺激的血浆胆囊收缩素从4.5 /-1.6增至7.6 /-1.0 pmol / L( P <.05)。结论是尽管餐后胆囊收缩素释放增强,洛哌丁胺抑制基础和氨基酸刺激的胆囊运动以及十二指肠内胆红素和淀粉酶的输出。

  • 【通过A(3)受体和CaMKII刺激2-Cl-IB-MECA分泌ANP。】 复制标题 收藏 收藏
    DOI:10.1016/j.peptides.2008.09.003 复制DOI
    作者列表:Yuan K,Bai GY,Park WH,Kim SZ,Kim SH
    BACKGROUND & AIMS: :Adenosine is a potent mediator of myocardial protection against hypertrophy via A(1) or A(3) receptors that may be partly related to atrial natriuretic peptide (ANP) release. However, little is known about the possible involvement of the A(3) receptor on ANP release. We studied the effects of the A(3) receptor on atrial functions and its modification in hypertrophied atria. A selective A(3) receptor agonist, 2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (2-CI-IB-MECA), was perfused into isolated, beating rat atria with and without receptor modifiers. 2-CI-IB-MECA dose-dependently increased the ANP secretion, which was blocked by the A(3) receptor antagonist, but the increased atrial contractility and decreased cAMP levels induced by 30muM 2-CI-IB-MECA were not affected. The 100muM 2-(1-hexylnyl)-N-methyladenosine (HEMADO) and N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (IB-MECA), A(3) receptor agonist, also stimulated the ANP secretion without positive inotropy. The potency for the stimulation of ANP secretion was 2-CI-IB-MECA>IB-MECA=HEMADO. The inhibition of the ryanodine receptor or calcium/calmodulin-dependent kinase II (CaMKII) attenuated 2-CI-IB-MECA-induced ANP release, positive inotropy, and translocation of extracellular fluid. However, the inhibition of L-type Ca(2+) channels, sarcoplasmic reticulum Ca(2+)-reuptake, phospholipase C or inositol 1,4,5-triphosphate receptors did not affect these parameters. 2-CI-IB-MECA decreased cAMP level, which was blocked only with an inhibitor of CaMKII or adenylyl cyclase. These results suggest that 2-CI-IB-MECA increases the ANP secretion mainly via A(3) receptor activation and positive inotropy by intracellular Ca(2+) regulation via the ryanodine receptor and CaMKII.
    背景与目标: :腺苷是心肌通过A(1)或A(3)受体对抗肥大的有效保护介质,而A(1)或A(3)受体可能与心钠素的释放有关。但是,关于A(3)受体可能参与ANP释放的消息鲜为人知。我们研究了A(3)受体对心房功能及其在肥大心房中的修饰的影响。将选择性A(3)受体激动剂2-氯-N(6)-(3-碘苄基)腺苷5'-N-甲基脲酰胺(2-CI-IB-MECA)灌注到孤立的,搏动的大鼠心房中而且没有受体修饰剂。 2-CI-IB-MECA剂量依赖性地增加了ANP的分泌,ANP的分泌被A(3)受体拮抗剂所阻断,但由30μM2-CI-IB-MECA诱导的心房收缩力的增加和cAMP水平的降低均未受到影响。也刺激了100μM的2-(1-己基)-N-甲基腺苷(HEMADO)和N(6)-(3-碘苄基)腺苷-5'-N-甲基脲酰胺(IB-MECA),A(3)受体激动剂。 ANP分泌无正性变质现象。刺激ANP分泌的效力为2-CI-IB-MECA> IB-MECA = HEMADO。 ryanodine受体或钙/钙调蛋白依赖性激酶II(CaMKII)的抑制作用减弱了2-CI-IB-MECA诱导的ANP释放,正性肌力和细胞外液易位。但是,L型Ca(2)通道,肌质网Ca(2)重新摄取,磷脂酶C或肌醇1,4,5-三磷酸受体的抑制不影响这些参数。 2-CI-IB-MECA降低了cAMP水平,仅被CaMKII或腺苷酸环化酶抑制剂所阻断。这些结果表明,2-CI-IB-MECA主要通过A(3)受体激活和通过胞内Ca(2)调控通过利安诺定受体和CaMKII来增加ANP分泌。
  • 【精囊少尿症:尿苷分泌低是脊柱神经创伤不育的生物标志物。】 复制标题 收藏 收藏
    DOI:10.1373/clinchem.2008.112219 复制DOI
    作者列表:Maher AD,Patki P,Lindon JC,Want EJ,Holmes E,Craggs M,Nicholson JK
    BACKGROUND & AIMS: BACKGROUND:Compromised sexual health is a major rehabilitative barrier for men with lower-spinal cord injury (SCI). Although studies have revealed decreased sperm motility, the quantitative biochemical changes that underlie the infertility mechanism remain poorly understood. METHODS:We employed a nontargeted approach combining 800 MHz hydrogen nuclear magnetic resonance ((1)H NMR) spectroscopy and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) with pattern recognition methods to analyze seminal fluid metabolite profiles in 10 men with and 8 without SCI above thoracic vertebra 10 (T10). RESULTS:The metabolic phenotype for SCI could be predicted from the (1)H NMR data. The median concentration of uridine in fertile controls was 1.55 mmol/L (range 1.0-5.0 mmol/L), but was undetectable by both NMR and MS in all but 2 individuals from the SCI group, one who later fathered a child without assisted fertility techniques. CONCLUSIONS:We hypothesize that uridine is likely to be an essential precursor to metabolites required for capacitation and is a potential marker for the prognosis of post-SCI functional fertility recovery. We derived the term "seminal oligouridinosis" to describe this newly identified condition.
    背景与目标: 背景:性健康受损是下脊髓脊髓损伤(SCI)男性的主要康复障碍。尽管研究表明精子活力下降,但不孕机制背后的定量生化变化仍知之甚少。
    方法:我们采用了一种非靶向方法,结合了800 MHz氢核磁共振波谱((1)H NMR)和超高效液相色谱-质谱(UPLC-MS)以及模式识别方法,以分析10名男性的精液代谢产物概况。 8在胸椎10(T10)上方没有SCI。
    结果:可以通过(1)H NMR数据预测SCI的代谢表型。受精对照中尿苷的中位浓度为1.55 mmol / L(范围为1.0-5.0 mmol / L),但除了SCI组的2名患者外,其他所有患者均无法通过NMR和MS检测到,该患者后来生下了一个没有辅助生育能力的孩子技术。
    结论:我们假设尿苷可能是获能所需代谢产物的重要前体,并且是SCI后功能生育能力恢复的预后指标。我们衍生出术语“先天性寡尿尿症”来描述这种新发现的疾病。
  • 【新兴范例?效应子分泌前的RxLR切割。】 复制标题 收藏 收藏
    DOI:10.1105/tpc.17.00454 复制DOI
    作者列表:Hofmann NR
    BACKGROUND & AIMS: -2
    背景与目标: -2

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