BACKGROUND & AIMS: :The distribution of calcitonin gene-related peptide (CGRP), enkephalin, galanin, neuropeptide Y (NPY), somatostatin, tachykinins and vasoactive intestinal polypeptide (VIP) was compared in cervical, thoracic, lumbar and sacral segmental levels of spinal cord and dorsal root ganglia of horse and pig. In both species, immunoreactivity for the peptides under study was observed at all segmental levels of the spinal cord. Peptide-immunoreactive fibres were generally concentrated in laminae I-III, the region around the central canal, and in the autonomic nuclei. A general increase in the number of immunoreactive nerve fibres was noted in the lumbosacral segments of the spinal cord, which was particularly exaggerated in the case of VIP immunoreactivity. In the horse, some CGRP-, somatostatin- or tachykinin-immunoreactive cell bodies were present in the dorsal horn. In the pig, cells immunoreactive for somatostatin, enkephalin or NPY were noted in a similar location. In the ventral horn most motoneurones were CGRP-immunoreactive in both species. However, in pig many other cell types were CGRP-immunoreactive not only in the ventral horn, but also in laminae V-VI of the dorsal horn. With the exception of enkephalin and NPY immunoreactivity, which was not seen in pig dorsal root ganglia, all peptides studied were localised to neuronal cell bodies and/or fibres in the dorsal root ganglia. In both species, immunolabeled cell bodies were observed in ganglia from cervical, thoracic, lumbar and sacral levels, with the exception of VIP-immunoreactive cells that were detected only in the lumbosacral ganglia. Numerous CGRP- and tachykinin-immunoreactive cell bodies were visualised in both species, while the cells immunolabeled with other peptide antisera were much lower in number. In both species, immunostaining of serial sections revealed that a subset of CGRP-immunoreactive cells co-expressed tachykinin, galanin or somatostatin immunoreactivity. In the horse some enkephalin-immunoreactive cells were also CGRP positive and occasionally combinations of three peptides, e.g. CGRP, tachykinin and galanin or CGRP, tachykinin and enkephalin were identified. The results obtained suggest that the overall pattern of distribution of peptide immunoreactivities is in general agreement with that so far described in other mammals, although some species variations have been observed, particularly regarding the presence of immunoreactive cell bodies in the dorsal horn of the spinal cord.

背景与目标： ：比较了降钙素基因相关肽（CGRP），脑啡肽，甘丙肽，神经肽Y（NPY），生长抑素，速激肽和血管活性肠多肽（VIP）在颈，胸，腰和部脊髓和背侧节段水平的分布马和猪的根神经节。在这两个物种中，在脊髓的所有节段水平上都观察到了所研究肽的免疫反应性。肽免疫反应性纤维通常集中在薄层I-III，中央管周围区域和自主神经核中。注意到在脊髓的腰s部中免疫反应性神经纤维的数量普遍增加，在VIP免疫反应性的情况下尤其明显。在马中，背角中存在一些CGRP，生长抑素或速激肽免疫反应性细胞体。在猪中，在相似的位置发现对生长抑素，脑啡肽或NPY具有免疫反应性的细胞。在腹角中，大多数运动神经元在这两个物种中均具有CGRP免疫反应活性。但是，在猪中，许多其他细胞类型不仅在腹角中而且在背角的层状V-VI中均具有CGRP免疫反应性。除了脑啡肽和NPY免疫反应性（在猪背根神经节中未见）外，所有研究的肽均位于背根神经节的神经元细胞体和/或纤维中。在这两个物种中，从颈部，胸部，腰部和部水平观察到的神经节中都有免疫标记的细胞体，只有在腰s神经节中才检测到VIP免疫反应性细胞。在这两个物种中都可以看到大量的CGRP和速激肽免疫反应性细胞体，而用其他肽抗血清进行免疫标记的细胞数量要低得多。在这两个物种中，连续切片的免疫染色显示，CGRP免疫反应性细胞的一部分共表达了速激肽，甘丙肽或生长抑素的免疫反应性。在马匹中，一些脑啡肽免疫反应性细胞也是CGRP阳性的，偶尔会结合三种肽，例如：确定了CGRP，速激肽和甘丙肽或CGRP，速激肽和脑啡肽。获得的结果表明，尽管已经观察到某些物种变异，特别是关于脊髓背角中免疫反应性细胞体的存在，但肽免疫反应性的总体分布模式与到目前为止在其他哺乳动物中描述的总体模式一致。 。

BACKGROUND & AIMS: Molecular dynamics simulations have been carried out with four polypeptides, Ala13, Val(13), Ser13, and Ala4Gly5Ala4, in vacuo and with explicit hydration. The unfolding of the polypeptides, which are initially fully alpha-helix in conformation, has been monitored during trajectories of 0.3 ns at 350 K. A rank of Ala < Val < Ser < Gly is found in the order of increasing rate of unwinding. The unfolding of Ala13 and Val(13) is completed in hundreds of picoseconds, while that of Ser13 is about one order of magnitude faster. The helix content of the peptide containing glycine residues falls to zero within a few picoseconds. Ramachandran plots indicate quite distinct equilibrium distributions and time evolution of dihedral angles in water and in vacuum for each residue type. The unfolding of polyalanine and polyvaline helices is accelerated due to solvation. In contrast, polyserine is more stable in water compared to vacuum, because its side chains can form intramolecular hydrogen bonds with the backbone more readily in vacuum, which disrupts the helix. Distribution functions of the spatial and angular position of water molecules in the proximity of the polypeptide backbone polar groups reveal the stabilization of the coiled structures by hydration. The transition from helix to coil is characterized by the appearance of a new peak in the probability distribution at a specific location characteristic of hydrogen bond formation between water and backbone polar groups. No significant insertion of water molecules is observed at the precise onset of unwinding, while (i, i+3) hydrogen bond formation is frequently detected at the initiation of alpha-helix unwinding.

背景与目标： 分子动力学模拟已经在真空和显着水合条件下用四种多肽Ala13，Val（13），Ser13和Ala4Gly5Ala4进行了。在350 K下0.3 ns的轨迹期间，已监测到最初完全为α-螺旋构型的多肽的解链。发现Ala

BACKGROUND & AIMS: :Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical. We have previously shown that 16-kDa fragments of the human prolactin/growth hormone (PRL/GH) family members are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments possess a 14-aa sequence having the characteristics of a tilted peptide. The tilted peptides of human prolactin and human growth hormone induce endothelial cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary formation both in vitro and in vivo. These antiangiogenic effects are abolished when the peptides' hydrophobicity gradient is altered by mutation. We further demonstrate that the well known tilted peptides of simian immunodeficiency virus gp32 and Alzheimer's beta-amyloid peptide are also angiogenesis inhibitors. Taken together, these results point to a potential new role for tilted peptides in regulating angiogenesis.

背景与目标： ：血管生成是包括肿瘤生长和转移在内的许多病理学中至关重要的一步。在这里，我们表明倾斜的肽发挥抗血管生成活性。倾斜（或倾斜定向）的肽是已知的使膜和脂质核心不稳定的短肽，其特征是当螺旋状时，疏水性残基沿轴不对称分布。我们以前已经表明，人类催乳激素/生长激素（PRL / GH）家族成员的16 kDa片段是有效的血管生成抑制剂。在这里，我们证明所有这些片段均具有具有倾斜肽特征的14-aa序列。人催乳激素和人生长激素的倾斜肽在体外和体内均可诱导内皮细胞凋亡，抑制内皮细胞增殖和抑制毛细血管形成。当肽的疏水性梯度因突变而改变时，这些抗血管生成作用被消除。我们进一步证明了猿猴免疫缺陷病毒gp32和阿尔茨海默氏β-淀粉样蛋白肽的众所周知的倾斜肽也是血管生成抑制剂。综上所述，这些结果表明倾斜的肽在调节血管生成中具有潜在的新作用。

BACKGROUND & AIMS: :Molecular dynamics simulations in explicit water were carried out for two stacks, each composed of six 10-strand antiparallel β-sheets for two peptides corresponding to the diverging turn of two homologous Abl-SH3 domains. The first system, referred to as 10×6×MK contained the DLSFMKGE sequence from the Drosophila, while the second one, referred to as 10×6×KK, contained the human DLSFKKGE sequence. It was found that the 10×6×MK β-sheet stack is stable, but the 10×6×KK β-sheet stack is not. The stability of the 10×6×MK β-sheet stack results from the hydrophobic interactions of the methionine and phenylalanine residues and the leucine residues of the neighboring sheets. The Met, Phe, and Leu hydrophobic units make a hydrophobic core for the stack of β-sheets. During the MD run, the Met, Phe, and Leu residues of the neighboring β-sheets acted as a conformational switch moving the β-sheets so that the Phe residue interacted with the Met residue from the neighboring β-sheet. Replacement of Met by Lys destroys the hydrophobic core, which is the stability factor of the β-sheet stack. For the 10×6×KK system, individual β-sheets were preserved during simulations, but the interactions between the β-sheets were lost. The calculations of a six β-sheet stack confirm the conclusion drawn from our earlier studies of single β-sheet systems that the β-sheets must form stacks to be stabilized. These results suggest that the two conserved basic residues at the diverging turn of SH3 domains could act as gatekeepers to avoid aggregation.

背景与目标： ：在显式水中对两个堆叠进行分子动力学模拟，每个堆叠由六个肽的十链反平行β-折叠组成，对应于两个同源Abl-SH3结构域的发散转向的两个肽。第一个系统称为10×6×MK，包含来自果蝇的DLSFMKGE序列，而第二个系统称为10×6×KK，包含人的DLSFKKGE序列。发现10×6×MKβ-折叠堆叠是稳定的，但是10×6×KKβ-折叠堆叠不是稳定的。 10×6×MKβ-折叠叠层的稳定性是由蛋氨酸和苯丙氨酸残基与相邻薄片的亮氨酸残基之间的疏水相互作用产生的。 Met，Phe和Leu疏水单元构成β-折叠堆叠的疏水核心。在MD运行期间，相邻β-折叠的Met，Phe和Leu残基充当构象开关，移动β-折叠，使Phe残基与来自相邻β-折叠的Met残基相互作用。 Lys取代Met会破坏疏水核，这是β-折叠堆叠的稳定性因素。对于10×6×KK系统，在模拟过程中保留了单独的β-折叠，但丢失了β-折叠之间的相互作用。六个β-折叠电池堆的计算证实了我们先前对单个β-折叠系统的研究得出的结论，即β-折叠必须形成要稳定的电池堆。这些结果表明，在SH3结构域的不同转弯处的两个保守的碱性残基可以充当看门人以避免聚集。

BACKGROUND & AIMS: :The ability of three primary amphipathic Cell-Penetrating Peptides (CPPs) CH3-CO-GALFLGFLGAAGSTMGAWSQPKKKRKV-NH-CH2-CH2-SH, CH3-CO-GALFLAFLAAALS LMGLWSQPKKKRKV-NH-CH2-CH2-SH, and CH3-CO-KETWWETWWTEWSQPKKKRKV-NH-CH2-CH2-SH called Pbeta, Palpha and Pep-1, respectively, to promote pore formation is examined both in Xenopus oocytes and artificial planar lipid bilayers. A good correlation between pore formation and their structural properties, especially their conformational versatility, was established. This work shows that the cell-penetrating peptides Pbeta and Pep-1 are able to induce formation of transmembrane pores in artificial bilayers and that these pores are most likely at the basis of their ability to facilitate intracellular delivery of therapeutics. In addition, their behaviour provides some information concerning the positioning of the peptides with respect to the membrane and confirms the role of the membrane potential in the translocation process.

背景与目标： ：三种主要两亲性细胞穿透肽（CPP）CH3-CO-GALFLGFLGAAGSTMGAWSQPKKKRKV-NH-CH2-CH2-CH，CH3-CO-GALFLAFLAAALS LMGLWSQPKKKRKV-NH-CH2-CH2-SH和CH3-CO-KETWWETWWTEWSQPKKKRKV-CPP的能力分别在非洲爪蟾卵母细胞和人工平面脂质双层中检测了分别称为Pbeta，Palpha和Pep-1的NH-CH2-CH2-SH来促进孔形成。建立了孔的形成与它们的结构特性，特别是它们的构象通用性之间的良好关联。这项工作表明细胞穿透肽Pbeta和Pep-1能够诱导人工双层中跨膜孔的形成，并且这些孔最有可能是基于其促进治疗剂向细胞内递送的能力。另外，它们的行为提供了有关肽相对于膜的定位的一些信息，并证实了膜电位在转运过程中的作用。

BACKGROUND & AIMS: Hemorphins are endogenous peptides belonging to the family of "nonclassical" or "atypical" opioid peptides. They are generated by enzymatic hydrolysis of the beta-, kappa-, delta-, or epsilon-chain of the blood protein hemoglobin. Originally, the hemorphins were isolated from enzymatically treated bovine blood. In recent years hemorphin structures have been identified as naturally occurring peptides in brain, plasma, and cerebrospinal fluid. This article will review recent studies of the hemorphins regarding their structures, mechanisms for their release, and their biological actions. A particular emphasis will be directed to their role in exercising human and their clinical relevance.

背景与目标： 血红蛋白是属于“非经典”或“非典型”阿片样肽家族的内源性肽。它们是通过酶水解血蛋白血红蛋白的β，κ，δ或ε链产生的。最初，血红素是从经酶处理的牛血中分离出来的。近年来，已将hemorphin结构鉴定为脑，血浆和脑脊髓液中的天然存在的肽。本文将回顾有关血红素的最新研究，涉及其结构，释放机理及其生物学作用。特别强调它们在锻炼人类中的作用及其临床意义。

BACKGROUND & AIMS: :Synthetic peptides, peptides A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)) and B (Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)), derived from the beetle Allomyrina dichotoma defensin, have antimicrobial activities. Immunotoxicological effect of these peptides was evaluated by cytotoxicity of mouse peritoneal macrophages. In addition, antigenicity of these peptides was studied by evaluating antibody responses in mice immunized with these peptides. The toxicity of peptide A toward mouse peritoneal cells was less than that of polymyxin B, when morphologically evaluated in a cytotoxicity test. Almost all of mice injected intraperitoneally (i.p.) with either peptide A or B at 50-150 mg/kg survived, whereas all mice injected i.p. with polymyxin B at the doses of more than 25 mg/kg died within 24 h. Interestingly, almost all of mice injected intravenously with these peptides at the doses of 10 and 25 mg/kg also survived. Furthermore, mice immunized with these peptides conjugated with keyhole limpet hemocyanin (KLH) showed little or negligible anti-peptide A or B antibody production, although anti-KLH antibody was significantly produced. The results indicated that peptides A and B were less cytotoxic than polymyxin B and also had poor antigenicity to produce specific antibody in mice.

背景与目标： ：合成肽，肽A（Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH（2））和B（Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg -NH（2）），源自甲虫Allomyrina dichotoma防御素，具有抗菌活性。通过小鼠腹膜巨噬细胞的细胞毒性评估了这些肽的免疫毒性作用。另外，通过评估用这些肽免疫的小鼠中的抗体应答来研究这些肽的抗原性。当在细胞毒性试验中进行形态学评估时，肽A对小鼠腹膜细胞的毒性小于多粘菌素B的毒性。几乎所有腹膜内（i.p.）注射50-150 mg / kg肽A或B的小鼠均存活，而所有腹膜内注射的小鼠均以50-150 mg / kg的剂量存活。剂量超过25 mg / kg的多粘菌素B在24小时内死亡。有趣的是，几乎所有以10和25 mg / kg的剂量静脉注射这些肽的小鼠都存活了下来。此外，用这些与锁孔戚血蓝蛋白（KLH）缀合的肽免疫的小鼠显示出很少或可忽略的抗肽A或B抗体产生，尽管产生了明显的抗KLH抗体。结果表明，肽A和B的细胞毒性低于多粘菌素B，并且在小鼠中产生特异性抗体的抗原性也较差。

BACKGROUND & AIMS: AIM:Biomarkers predicting sustained virological response (SVR) to pegylated interferon-α plus ribavirin (PEG IFN-α/RBV) were investigated. METHODS:Peptides in pretreatment sera from 107 patients with hepatitis C virus (HCV) genotype 1 were comprehensively analyzed by mass spectrometry. Ion intensity of the peptides was used to generate discriminant models between the responders who achieved SVR (R) and the non-responders (NR) to PEG IFN-α/RBV. RESULTS:In total, 107 peptides were detected in a training set (n = 23). A discriminant model using a peptide, complement 3f des-arginine (C3f-dR), showed sensitivity of 35% and specificity of 94% for SVR prediction in a testing set (n = 68). In all the R and NR (n = 96), an area under the receiver-operator curve (AUROC) of 0.64 in the C3f-dR model was increased to 0.78 by addition of platelet (PLT) counts (C3f-dR/PLT model). Another model using the 107 peptides (AUROC, 0.77) also showed higher AUROC (0.79) by addition of hemoglobin (Hb), body mass index (BMI) and age (107P/Hb/BMI/Age model). The sensitivity and specificity of the C3f-dR/PLT model were 59% and 88%, and those of the 107P/Hb/BMI/Age model were 70% and 92%, respectively. The C3f-dR/PLT model showed high AUROC (0.82), similar to that of interleukin-28B rs8099917 genotype analysis (0.86) in the 45 tested patients. Prediction by the combination of the C3f-dR/PLT model, the 107P/Hb/BMI/Age model and the rs8099917 genotype analysis was accurate in 44 out of the 45 patients (AUROC, 0.95). CONCLUSION:Serum peptides, especially C3f-dR, would be useful predictors for SVR to PEG IFN-α/RBV. The complements may be involved in the HCV elimination.

背景与目标： 目的：研究了预测对聚乙二醇化干扰素-α和利巴韦林（PEGIFN-α/ RBV）持续病毒学应答（SVR）的生物标志物。
方法：采用质谱法对107例丙型肝炎病毒（HCV）基因1型患者血清中的多肽进行了综合分析。肽的离子强度用于在获得SVR（R）的应答者和对PEGIFN-α/ RBV的无应答者（NR）之间生成判别模型。
结果：在一个训练集中总共检测到107个肽（n = 23）。使用肽补体3f des-精氨酸（C3f-dR）的判别模型在测试集中对SVR的预测显示35％的敏感性和94％的特异性（n = 68）。在所有R和NR（n = 96）中，通过添加血小板（PLT）计数（C3f-dR / PLT模型），在C3f-dR模型中，接收者-操作者曲线下的面积（AUROC）为0.64。 ）。另一种使用107种肽的模型（AUROC，0.77）通过添加血红蛋白（Hb），体重指数（BMI）和年龄（107P / Hb / BMI / Age模型）也显示出较高的AUROC（0.79）。 C3f-dR / PLT模型的敏感性和特异性分别为59％和88％，而107P / Hb / BMI / Age模型的敏感性和特异性分别为70％和92％。 C3f-dR / PLT模型在45位接受测试的患者中显示出较高的AUROC（0.82），与白细胞介素28B rs8099917基因型分析（0.86）相似。通过对C3f-dR / PLT模型，107P / Hb / BMI / Age模型和rs8099917基因型分析的组合进行的预测在45例患者中有44例是准确的（AUROC，0.95）。
结论：血清肽，特别是C3f-dR，将成为SVR转化为PEGIFN-α/ RBV的有用预测因子。补体可能参与HCV的消除。

BACKGROUND & AIMS: :An experimentally based, quantitative understanding of the entrapment and function of small peptides within PEO brush layers does not currently exist. Earlier work provided a rationale for expecting that an ordered, compact peptide will enter the PEO phase more readily than a peptide of similar size that adopts a less ordered, less compact form, and that amphiphilicity will promote peptide retention within the hydrophobic region of the PEO brush. Here we more deliberately describe criteria for peptide integration and structural change within the PEO brush, and discuss the reversibility of peptide entrapment with changing solvent conditions. For this purpose, circular dichroism (CD) was used to record the adsorption and conformational changes of (amphiphilic) WLBU2 and (non-amphiphilic) polyarginine peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. Peptide conformation was controlled between disordered and α-helical forms by varying the concentration of perchlorate ion. We show an initially more ordered (α-helical) structure promotes peptide adsorption into the PEO layer. Further, a partially helical peptide undergoes an increase in helicity after entry, likely due to concomitant loss of capacity for peptide-solvent hydrogen bonding. Peptide interaction with the PEO chains resulted in entrapment and conformational change that was irreversible to elution with changing solution conditions in the case of the amphiphilic peptide. In contrast, the adsorption and conformational change of the non-amphiphilic peptide was reversible. These results indicate that responsive drug delivery systems based on peptide-loaded PEO layers can be controlled by modulation of solution conditions and peptide amphiphilicity.

背景与目标： ：目前尚不存在基于实验的定量了解PEO刷层中小肽的捕获和功能的方法。较早的工作提供了一个理由，可以预期有序的紧凑型肽会比采用无序的，紧凑型形式的类似大小的肽更容易进入PEO相，并且两亲性将促进肽保留在PEO的疏水区内刷子。在这里，我们更加刻意地描述了PEO刷内肽整合和结构变化的标准，并讨论了随着溶剂条件的变化，肽截留的可逆性。为此，使用圆二色性（CD）记录了（两亲）WLBU2和（非两亲）聚精氨酸肽在未包被（疏水）和PEO包被的二氧化硅纳米粒子上的吸附和构象变化。通过改变高氯酸根离子的浓度，可以控制无序和α-螺旋形式之间的肽构象。我们显示出最初更有序的（α螺旋）结构可促进肽吸附到PEO层中。此外，部分螺旋的肽进入后螺旋度增加，这可能是由于肽-溶剂氢键合能力的同时丧失。肽与PEO链的相互作用导致截留和构象变化，在两亲性肽的情况下，随着溶液条件的变化，洗脱是不可逆的。相反，非两亲性肽的吸附和构象变化是可逆的。这些结果表明，可以通过调节溶液条件和肽两亲性来控制基于载有肽的PEO层的响应性药物递送系统。

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。

BACKGROUND & AIMS: BACKGROUND:N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict cardiovascular outcome in many settings. There are very few data assessing the utility of NT-proBNP concentrations in the prediction of long-term outcome after cardiac surgery. We assessed the ability of NT-proBNP to predict 3 yr mortality compared with validated clinical risk prediction tools. METHODS:A secondary analysis of a prospectively recruited patient cohort of 1010 patients undergoing cardiac surgery. Baseline clinical details were obtained including EuroSCORE. Multi-variable modelling, area under the receiver operating characteristic curves (AUCs), and net reclassification improvement were utilized. RESULTS:NT-proBNP was a univariable predictor of 3 yr mortality but was no longer a significant predictor in a multivariable model (hazard ratio 1.00 per 250 ng litre(-1), 95% confidence interval 0.98-1.02, P=0.80). The relative and additive predictive values of the preoperative EuroSCORE (both additive and logistic versions) and NT-proBNP concentrations were compared. All were predictive of 3 yr mortality (P<0.001) with almost identical AUCs (0.71 for EuroSCORE, 0.70 for NT-proBNP). When either the EuroSCORE or NT-proBNP concentrations are known, the addition of the other does not improve the ability to predict 3 yr mortality. CONCLUSIONS:Preoperative NT-proBNP concentrations and the EuroSCORE have equivalent, and moderate, predictive accuracy for mortality 3 yr after cardiac surgery. EuroSCORE uses clinical data but is not routinely used for individual clinical risk prediction. NT-proBNP measurement would incur additional costs but can be measured quickly and objectively. With such similar predictive accuracy, factors such as the ease of calculation and cost will likely determine their use in clinical practice.

背景与目标： 背景：N末端前B型利钠肽（NT-proBNP）的浓度可预测许多情况下的心血管预后。很少有数据评估NT-proBNP浓度在预测心脏手术后的长期预后方面的效用。与经过验证的临床风险预测工具相比，我们评估了NT-proBNP预测3年死亡率的能力。
方法：对1010名接受心脏手术的患者的前瞻性患者队列进行二次分析。获得了包括EuroSCORE在内的基线临床详细信息。利用多变量建模，接收器工作特征曲线（AUC）下方的面积以及净重分类改进。
结果：NT-proBNP是3年死亡率的单变量预测指标，但在多变量模型中已不再是重要的预测指标（每250 ng升（-1）的危险比1.00，95％置信区间0.98-1.02，P = 0.80）。比较术前EuroSCORE（相加版本和逻辑版本）和NT-proBNP浓度的相对和相加预测值。所有这些都可以预测3年死亡率（P <0.001）和几乎相同的AUC（EuroSCORE为0.71，NT-proBNP为0.70）。当已知EuroSCORE或NT-proBNP浓度时，添加其他浓度并不能提高预测3年死亡率的能力。
结论：术前NT-proBNP浓度和EuroSCORE对心脏手术后3年死亡率具有同等的，中等的预测准确性。 EuroSCORE使用临床数据，但通常不用于个别临床风险预测。 NT-proBNP测量会产生额外费用，但可以快速而客观地进行测量。在具有类似的预测准确性的情况下，诸如易计算性和成本之类的因素很可能会决定其在临床实践中的用途。

BACKGROUND & AIMS: UNLABELLED:Heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. Serum B-type natriuretic peptide (BNP) plays an important role in the diagnosis of HF. Therefore, we hypothesized that BNP would be useful in the differential diagnosis of ascites. Consecutive patients with new onset ascites were prospectively enrolled in this cross-sectional study. All patients had measurements of serum-ascites albumin gradient (SAAG), total protein concentration in ascitic fluid, serum, and ascites BNP. We enrolled 218 consecutive patients with ascites resulting from HF (n = 44), cirrhosis (n = 162), peritoneal disease (n = 10), and constrictive pericarditis (n = 2). Compared to SAAG and/or total protein concentration in ascites, the test that best discriminated HF-related ascites from other causes of ascites was serum BNP. A cutoff of >364 pg/mL (sensitivity 98%, specificity 99%, and diagnostic accuracy 99%) had the highest positive likelihood ratio (168.1); that is, it was the best to rule in HF-related ascites. Conversely, a cutoff ≤ 182 pg/mL had the lowest negative likelihood ratio (0.0) and was the best to rule out HF-related ascites. These findings were confirmed in a 60-patient validation cohort. CONCLUSIONS:Serum BNP is more accurate than ascites analyses in the diagnosis of HF-related ascites. The workup of patients with new onset ascites could be streamlined by obtaining serum BNP as an initial test and could forego the need for diagnostic paracentesis, particularly in cases where the cause of ascites is uncertain and/or could be the result of HF.

背景与目标： 肝硬化后，心力衰竭（HF）是引起腹水的第二大常见原因。血清B型利钠肽（BNP）在HF的诊断中起重要作用。因此，我们假设BNP在腹水的鉴别诊断中将是有用的。连续有新发腹水的患者前瞻性地参与了这项横断面研究。所有患者均测量血清腹水白蛋白梯度（SAAG），腹水，血清和腹水BNP中的总蛋白浓度。我们招募了218位连续的因HF（n = 44），肝硬化（n = 162），腹膜疾病（n = 10）和缩窄性心包炎（n = 2）引起的腹水患者。与SAAG和/或腹水中的总蛋白浓度相比，最能区分HF相关性腹水与其他腹水原因的测试是血清BNP。 > 364 pg / mL的临界值（灵敏度98％，特异性99％和诊断准确度99％）具有最高的阳性似然比（168.1）；也就是说，这是最好的HF相关腹水。相反，临界值≤182 pg / mL具有最低的负似然比（0.0），是排除HF相关腹水的最佳方法。这些发现在60名患者的验证队列中得到了证实。
结论：血清BNP在腹水相关性腹水的诊断中比腹水分析更准确。可以通过获取血清BNP作为初始检测来简化新发腹水患者的检查工作，并且可以放弃诊断性穿刺术的需要，尤其是在腹水原因不确定和/或可能是HF的情况下。

BACKGROUND & AIMS: :Members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors have been reported to be up-regulated in Alzheimer's disease. In the present study, we have investigated the effects of amyloid-beta (Abeta) peptides on C/EBPbeta and C/EBPdelta, previously shown to be induced by inflammatory stimuli in glial cells. Surprisingly, electrophoretic mobility shift assay showed that both Abeta(1-42) and Abeta(25-35) blocked C/EBP activation induced by the inflammatory cytokine interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS) in mixed primary glial cell cultures from rat. Abeta also blocked IL-1beta- or LPS-induced C/EBP protein levels. The most prominent effects were observed on DNA binding activity and protein levels of C/EBPdelta. Our results demonstrate a dysregulation of C/EBP when glial cells are activated in the presence of Alzheimer Abeta peptides.

背景与目标： ：据报道，转录因子CCAAT /增强子结合蛋白（C / EBP）家族的成员在阿尔茨海默氏病中被上调。在本研究中，我们已经研究了淀粉样β（Abeta）肽对C / EBPbeta和C / EBPdelta的影响，先前已证明是由神经胶质细胞中的炎症刺激诱导的。出乎意料的是，电泳迁移率变动分析表明，Abeta（1-42）和Abeta（25-35）均阻断了混合性原代神经胶质细胞中炎性细胞因子白介素-1β（IL-1beta）或脂多糖（LPS）诱导的C / EBP活化来自大鼠的文化。 Abeta还阻断了IL-1beta或LPS诱导的C / EBP蛋白水平。在DNA结合活性和C / EBPdelta的蛋白质水平上观察到最显着的影响。我们的结果证明，在存在Alzheimer Abeta肽的情况下激活神经胶质细胞时，C / EBP失调。

BACKGROUND & AIMS: BACKGROUND:Uroguanylin and guanylin are intestinal peptides that activate a receptor-guanylate cyclase, which is also a receptor for Escherichia coli heat-stable enterotoxin (STa). These peptides may have a role in the body's regulation of fluid and electrolytes.

METHODS:STa, bioactive guanylin, and bioactive uroguanylin were evaluated for effects in: 1) the suckling mouse intestinal fluid secretion assay; 2) an in vitro suckling mouse intestinal loop assay; 3) an intestinal receptor autoradiography assay; 4) a control or agonist-stimulated assay for cGMP response in T84 cells; and 5) an in vivo renal function assay in mice.

RESULTS:In vivo, orally administered uroguanylin and STa but not guanylin, stimulated intestinal fluid secretion. All three peptides activated intestinal guanylate cyclase and had common intestinal receptors. In vitro, after pretreatment with chymotrypsin, only uroguanylin and STa retained agoinst activity. Chymostatin preserved guanylin activity. STa and uroguanylin induced diuresis, natriuresis, and kaliuresis. Guanylin was less potent than uroguanylin and STa.

CONCLUSIONS:The results suggest that the endogenous intestinal peptides, uroguanylin and guanylin, regulate water and electrolyte homeostasis both through local effects on intestinal epithelia and endocrine effects on the kidney.

背景与目标： 背景：尿鸟嘌呤和鸟嘌呤是激活受体鸟苷酸环化酶的肠肽，鸟苷酸环化酶也是大肠杆菌热稳定肠毒素（STa）的受体。这些肽可能在人体对液体和电解质的调节中起作用。

方法：评估了STa，生物活性鸟苷和生物活性尿鸟苷在以下方面的作用：1）乳鼠肠道液体分泌测定； 2）体外乳鼠肠道环测定； 3）肠受体放射自显影测定； 4）T84细胞中cGMP应答的对照或激动剂刺激测定； 5）在小鼠体内进行肾功能测定。

结果：体内口服尿鸟苷和STa而非鸟苷刺激肠道液体分泌。所有这三种肽均激活肠鸟苷酸环化酶并具有共同的肠受体。在体外，用胰凝乳蛋白酶预处理后，仅尿鸟苷和STa保留了先前的活性。胰凝乳蛋白酶抑制蛋白保留了鸟苷蛋白活性。 STa和尿鸟苷蛋白可引起利尿，利钠和利尿。结论：结果表明，内源性肠肽尿鸟苷和鸟苷能通过局部作用于肠上皮细胞和内皮细胞来调节水和电解质的体内稳态。内分泌对肾脏的影响。