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。