Nutritional Immunity: S100 Proteins at the Host-Pathogen Interface

The S100 family of EF-hand calcium (Ca²⁺)-binding proteins is essential for a wide range of cellular functions. During infection, certain S100 proteins act as damage-associated molecular patterns (DAMPs) and interact with pattern recognition receptors to modulate inflammatory responses. In addition, these inflammatory S100 proteins have potent antimicrobial properties and are essential components of the immune response to invading pathogens. In this review, we focus on S100 proteins that exhibit antimicrobial properties through the process of metal limitation, termed nutritional immunity, and discuss several recent advances in our understanding of S100 protein-mediated metal sequestration at the site of infection.     

Myeloperoxidase-dependent Lipid Peroxidation Promotes the Oxidative Modification of Cytosolic Proteins in Phagocytic Neutrophils

Phagocytic neutrophils generate reactive oxygen species to kill microbes. Oxidant generation occurs within an intracellular phagosome, but diffusible species can react with the neutrophil and surrounding tissue. To investigate the extent of oxidative modification, we assessed the carbonylation of cytosolic proteins in phagocytic neutrophils. A 4-fold increase in protein carbonylation was measured within 15 min of initiating phagocytosis. Carbonylation was dependent on NADPH oxidase and myeloperoxidase activity and was inhibited by butylated hydroxytoluene and Trolox, indicating a role for myeloperoxidase-dependent lipid peroxidation. Proteomic analysis of target proteins revealed significant carbonylation of the S100A9 subunit of calprotectin, a truncated form of Hsp70, actin, and hemoglobin from contaminating erythrocytes. The addition of the reactive aldehyde 4-hydroxynonenal (HNE) caused carbonylation, and HNE-glutathione adducts were detected in the cytosol of phagocytic neutrophils. The post-translational modification of neutrophil proteins will influence the functioning and fate of these immune cells in the period following phagocytic activation, and provides a marker of neutrophil activation during infection and inflammation.     

Isolation and characterization of latent and active polyphenoloxidase in BRS Clara (CNPUV 154-147 × Centennial seedless) and BRS Morena (Marroo seedless × Centennial seedless) seedless table grapes

The seedless grapes BRS Clara and BRS Morena, developed in Brazil, are currently growing in popularity due to their premium texture and taste. However, there are no reports on the polyphenoloxidase (PPO) from these cultivars. In this paper, active and latent PPO from BRS Clara and BRS Morena seedless grapes were extracted using the non-ionic detergents Triton-X-100 (active) and Triton-X-114 (latent), and their catecholase activities were characterized. The PPO extracted using Triton-X-110 exhibited maximum activities at pH 6.0 and at 25 °C. Above 30 °C, a gradual decline in activities was noted, with complete inactivation at 60 °C. The PPO from grapes extracted with Triton-X-114 was activated with 0.2% of the ionic detergent sodium dodecyl sulfate (SDS), and exhibited maximum activities at pH 5.5 and at 30 °C. It was stable until the temperature reached 60 °C.     

血S100B蛋白和尿乳酸/肌酐比值对门静脉高压症术后肝性脑病发生的早期预测价值

目的评价血S100B蛋白和尿乳酸/肌酐对乙肝肝硬化门脉高压症术后肝性脑病发生的早期预测价值。方法回顾性分析65例乙肝肝硬化门脉高压症患者的临床资料,动态检测术后24、48和72h的血S100B蛋白和尿乳酸/肌酐比值水平,根据是否发生术后肝性脑病将受试者分为肝性脑病组与非肝性脑病组,并对肝性脑病组患者进行临床分度。结果乙肝肝硬化门脉高压症患者术后发生肝性脑病组72h内血S100B蛋白含量和24 h内尿乳酸/肌酐比值水平明显高于非肝性脑病组(P<0.001);72h内血S100B蛋白含量和24 h内尿乳酸/肌酐比值之间及与肝性脑病的临床分度呈正相关(P<0.001);当血S100B水平在28ng/L,尿乳酸/肌酐比值在0.47时,单独检测72h血S100B蛋白的敏感度、特异度分别为91.2%、93.6%;尿乳酸/肌酐比值预测肝性脑病的敏感度和特异性度以术后24h最高,分别为89.3%和91.7%;如检测72h血S100B蛋白的同时监测术后24h尿乳酸/肌酐比值可显著提高肝性脑病诊断的准确性,联合应用两项指标进行检测,诊断的敏感度和特异度分别为95.7%和98.6%,较两种方法单独应用敏感度和特异度均提高。结论对门静脉高压症患者术后以临床表现为基础,同时监测72h内血S100B蛋白和24h尿乳酸/肌酐比值,对提高术后肝性脑病的早期诊断和临床分度具有一定应用价值。     

Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease

Background

The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4. These cells are also present in the basal epithelium. Such changes are likely hallmarks of epithelial mesenchymal transition (EMT). We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.

Methods

Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells). The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope". Slides were double stained for S100A4 and cytokeratin(s).

Results

In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003. Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003. Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.

Conclusions

These data provide additional support for active EMT in COPD airways.     

S100A4在胰腺癌中的研究进展

胰腺癌最重要的生物学特性是容易发生转移和侵袭,致使很多患者无法得到根治性治疗。外科手术是胰腺癌惟一可能治愈的手段,但仅有10-20%的患者有机会手术治疗。错过早期诊断、常规疗法普遍不明显及快速肿瘤扩散共同导致患者的预后不良。胰腺癌的发生、发展受多基因调控。S100A4基因是近几年发现的一种具有促肿瘤作用的基因,目前研究认为该蛋白在胰腺癌的侵袭和转移中起重要作用.本文主要就S100A4与胰腺癌的有关研究进展加以综述。     

S100A11在结肠癌的表达及其与临床特征的关系

目的:探讨S100A11在结肠癌和正常肠粘膜组织中的表达及其与患者临床特征的的关系。方法:采用RT-PCR、WesternBlotting技术,检测S100A11在24例结肠癌及正常肠粘膜中的表达,并分析S100A11与患者年龄,性别,临床病理分型之间的关系。结果:S100A11mRNA在结肠癌组织的表达量(0.944+0.032)高于正常肠粘膜组织中的表达量(0.828+0.079),两组比较差异有统计学意义(p<0.05)。S100A11蛋白在结肠癌组织中的表达量(0.951+0.02)高于在正常肠粘膜组织中的表达量(0.860+0.05),两组比较差异有统计学意义(p<0.05)。但与患者临床特征之间比较差异无统计学意义(p>0.05)。结论:S100A11在结肠癌组织中表达量高于正常肠粘膜组织,提示其与结肠癌的发生和发展有关.是判断结肠癌生物学行为的有价值的参考指标。     

新生儿缺氧缺血性脑病血清S-100B蛋白与NBNA评分动态监测 的临床研究

目的:观察新生儿缺氧缺血性脑病(hypoxic-ischemicencephalopathy,HIE)血清S-100B蛋白的动态变化规律,探讨其在HIE早期诊断中的价值,以及其浓度变化与病情严重程度及预后的关系。同时研究围产期高危因素以及NBNA评分在HIE发生发展与预后中的作用。方法:30例住院正常新生儿作为对照组,于出生后采血,55例HIE患儿(HIE组)分别于出生后1天、2天、7天采血,采用酶联免疫吸附试验、双抗体夹心法检测。收集并分析两组围产期相关资料。HIE组并于采血同时进行NBNA评分。结果:(1)HIE患儿生后第一天与第二天血清S-100B蛋白浓度明显高于对照组(P<0.05),生后第七天轻度HIE与对照组比较没有统计意义,中、重度HIE与对照组比较有统计学意义。(2)生后第一天与第二天不同病情组HIE患儿NBNA评分相互比较差异具有统计学意义(P<0.05),第七天轻、中和重度患儿NBNA评分<35分的患儿分别占33.3%,47.1%,100%。结论:动态监测HIE患儿血清S-100B蛋白浓度和NBNA评分的变化,对HIE的早期诊断,严重程度的判断以及预后的估计有重要意义。     

S100A4与肿瘤细胞增殖及凋亡的研究进展

转移相关蛋白S100A4属于S100钙离子结合蛋白超家族,有着共同的EF手型功能区来介导其活性。S100A4在众多肿瘤生物学行为中起着调节作用。而且,S100A4在不同类型的肿瘤患者扮演着判断预后的角色。目前研究认为其与肿瘤细胞运动、增殖、刺激血管生成及基质重建有关系。本文就S100A4生物学特性及其对肿瘤细胞增殖、凋亡中的作用和可能机制作一综述。     

Life-Cycle Assessment of Biosolids Processing Options

Biosolids, also known as sewage sludge, are reusable organic materials separated from sewage during treatment. They can be managed in a variety of ways. Different options for biosolids handling in Sydney, Australia, are compared in this study using life-cycle assessment. Two key comparisons are made: of system scenarios (scenario 1 is local dewatering and lime amendment; scenario 2 is a centralized drying system) and of technologies (thermal drying versus lime amendment). The environmental issues addressed are energy consumption, global warming potential (GWP), and human toxicity potential (HTP).
Scenario 2 would consume 24% more energy than scenario 1. This is due to the additional electricity for pumping and particularly the petrochemical methane that supplements biogas in the drier. A centralized system using the same technologies as scenario 1 has approximately the same impacts. The GWP and HTP of the different scenarios do not differ significantly.
The assessment of technology choices shows significant differences. The ample supply of endogenous biogas at North Head sewage treatment plant for the drying option allows reductions, relative to the lime-amendment option, of 68% in energy consumption, 45% in GWP, and 23% in HTP.
Technology choices have more significant influence on the environmental profile of biosolids processing than does the choice of system configurations. Controlling variables for environmental improvement are the selection of biogas fuel, avoidance of coalsourced electrical energy, minimization of trucking distances, and raising the solids content of biosolids products.