Dynamic changes in serum angiopoietin-1, angiopoietin-2, and angiopoietin-2/angiopoietin-1 ratio in acute myocardial infarction patients treated with primary percutaneous coronary intervention

Context: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play divergent roles in myocardial ischemia and reperfusion injury.

Objective: To investigate serum Ang-1 and Ang-2 levels in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI).

Methods: Serum Ang-1 and Ang-2 were measured in 85 STEMI patients in the first week after PCI.

Results: Ang-1, Ang-2 and Ang-2/Ang-1 ratio (Ang-2/1) were all increased at admission, and had dynamic changes after PCI. Ang-2 and Ang-2/1 at admission and 2 h after PCI were positively correlated with peak cardiac troponin T levels.

Conclusion: The extent of myocardial damage may be linked to circulating Ang-2 and Ang-2/1.     

Changes and significance of serum angiopoietin-2 levels in patients with coronary heart disease

Coronary heart disease (CHD) is characterized by inflammatory process and endothelial dysfunction. To investigate angiopoietin-2 (Ang-2) profiles, we evaluated serum Ang-2 levels in different types of CHD in 166 subjects. Ang-2 was measured by enzyme-linked immunosorbent assay. Serum Ang-2 levels were significantly elevated in patients with CHD and gradually increased with advance of CHD. Ang-2 was positively correlated with Gensini scores and hs-CRP. Ang-2 might have potential implication in detecting and monitoring the progression of CHD.     

血浆血管生成素-2与ANCA相关性血管炎疾病活动性的相关性研究

目的探讨血浆血管生成素-2(Ang2)与ANCA相关性血管炎疾病活动的相关关系。方法将我院收治的41例ANCA相关性血管炎患者分为缓解期组(BVAS评分3分,n=18)和活动期组(BVAS评分≥15分,n=23),采用酶联免疫吸附试验(ELISA)比较两组血浆Ang2水平。结果活动期组ANCA相关性血管炎患者血浆Ang2水平明显升高,与缓期解组比较差异有统计学意义(P0.05);血浆Ang2水平与BVAS评分成明显正相关(r=-0.278,P0.01)。结论血浆Ang2有望成为评价ANCA相关性血管炎疾病活动的生物学标记物指标。     

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity

BACKGROUND: Psoriatic plaques have been shown to contain increased levels of proinflammatory cytokines. Serum levels of interleukin (IL)-6, IL-7, IL-8, and interferon (IFN)-gamma have been reported elevated in psoriatic patients. AIM: To evaluate serum cytokine profiles in psoriasis patients by improved enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. METHODS: We analyzed single serum samples from 10 patients with active untreated psoriasis, two patients with active treated psoriasis, and five healthy volunteers for major T helper type 1 and T helper type 2 cytokines using the LINCOplex ELISA multi-analyte detection system that permits simultaneous detection of multiple cytokines from a single sample. The disease severity, including erythema, induration, scale, and surface area, was assessed. RESULTS: IFN-gamma was markedly elevated in all sera from psoriasis patients, 33.8 +/- 1.3 pg/ml (mean +/- standard error) versus 8 +/- 1.5 pg/ml for normal controls (p < 0.01), and positively correlated with all indices of disease severity (Spearman r > 0.6). IL-8 was also increased in psoriasis patients (24.4 +/- 1.8 pg/ml) versus normal controls (3.6 +/- 1.2 pg/ml) (p < 0.05) and positively correlated with the degree of erythema (Spearman r > 0.6). Mean IL-12 levels were decreased in sera from psoriasis patients (8.5 +/- 1.2 pg/ml) compared with normal controls (42.2 +/- 5.3 pg/ml) (p < 0.01). Also, serum IL-10 levels were below detection levels in psoriatics compared with controls (6.4 +/- 1.3 pg/ml). CONCLUSIONS: This new ELISA system allowed rapid and reliable detection of numerous cytokines in single serum samples from patients with psoriasis. We observed that IFN-gamma and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased.     

Early increase of serum angiopoietin-2 are associated with early progression to death in experimental injury

Severe trauma induces systemic inflammatory response syndrome (SIRS) through the release of proinflammatory mediators. Angiopoietin-2 (Ang-2) is over-produced in sepsis and leads to dysfunction of endothelial cells and subsequent multiple organ dysfunction. In order to define the role of Ang-2 in lethal injury, 45 rabbits were studied; eight were administered anesthesia; 11 were sham-operated and 26 were subject to femoral injury. Concentrations of Ang-2, malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα) and endotoxins (LPS) were determined in serum and of Ang-2 in tissues; vital signs and overall survival were recorded. Bacterial growth was quantitatively assessed in liver, spleen and lung of animal that died. Survival of injured animals was shorter than sham operated ones. Serum concentrations of Ang-2 at 4 h was greater among animals where death supervened early, i.e. within 48 h after injury than among rabbits that died later. That was also the case for systolic, diastolic and mean arterial pressures. Serum MDA and TNFα and tissue bacterial growth did not differ between rabbits that died early and rabbits that died late. Serum LPS remained below the limit of detection. These results suggest that circulating Ang-2 participates in the pathogenesis of SIRS after injury connected with early haemodynamic instability.     

Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes

Background

We recently identified selenoprotein P (SeP) as a liver-derived secretory protein that causes insulin resistance in the liver and skeletal muscle; however, it is unknown whether and, if so, how SeP acts on adipose tissue. The present study tested the hypothesis that SeP is related to hypoadiponectinemia in patients with type 2 diabetes.

Methodology/Principal Findings

We compared serum levels of SeP with those of adiponectin and other clinical parameters in 36 patients with type 2 diabetes. We also measured levels of blood adiponectin in SeP knockout mice. Circulating SeP levels were positively correlated with fasting plasma glucose (r = 0.35, P = 0.037) and negatively associated with both total and high-molecular adiponectin in patients with type 2 diabetes (r = −0.355, P = 0.034; r = −0.367, P = 0.028). SeP was a predictor of both total and high-molecular adiponectin, independently of age, body weight, and quantitative insulin sensitivity index (β = −0.343, P = 0.022; β = −0.357, P = 0.017). SeP knockout mice exhibited an increase in blood adiponectin levels when fed regular chow or a high sucrose, high fat diet.

Conclusions/Significance

These results suggest that overproduction of liver-derived secretory protein SeP is connected with hypoadiponectinemia in patients with type 2 diabetes.     

Procalcitonin and cellulitis: correlation of procalcitonin blood levels with measurements of severity and outcome in patients with limb cellulitis

Background: Procalcitonin levels may be raised in bacterial infections and have been used to guide antibiotic therapy. There is little data on procalcitonin and limb cellulitis.

Objectives: Within a clinical trial of antibiotic therapy, we examined the correlation between clinical observations, blood tests and local measurements of skin damage, with serum procalcitonin levels.

Methods: The data is from a subset of the patients recruited into a clinical trial of antibiotic therapy for cellulitis (clindamycin for cellulitis, NCT01876628) whose procalcitonin levels were correlated with clinical and laboratory measurements. We selected the variables strongly correlated with procalcitonin and evaluated the predictive value of the baseline procalcitonin on the primary trial outcome.

Results: 136 patients provided 307 procalcitonin levels which were correlated with 8 variables. The strongest correlations (correlation coefficient of >0.5) with procalcitonin were the affected skin area (0.537), C-reactive protein (0.574) and neutrophil:lymphocyte ratio (0.567). Receiver operator characteristic curves demonstrated poor sensitivity and specificity of procalcitonin in predicting primary outcome. Procalcitonin baseline levels were low but decreased as patients recovered.

Conclusions: Procalcitonin levels are generally low in limb cellulitis and cannot be used to confirm the diagnosis or the need for antibiotic therapy. Procalcitonin is a poor predictor of early improvement.     

益生菌对稳定性冠心病患者血清TMAO水平的影响及与血清炎性因子水平的相关性

目的 探究益生菌对稳定性冠心病（SCAD）患者血清氧化三甲胺（TMAO）水平的影响及其与血清炎性因子水平的相关性。方法 选取我院2017年6月至2018年1月间诊断及治疗的SCAD患者74例,采用随机数表法分为益生菌组（37例）与对照组（37例）,对照组予以稳定型冠心病标准治疗,益生菌组在对照组的基础上口服益生菌制剂,金双歧,2 g/次,3次/d,疗程均为2个月,比较治疗前后患者血液中TMAO、TNF-α、IL-6、IL-8、CRP水平及大便中双歧杆菌载量,使用Pearson相关性分析模型探究细菌载量与TMAO、TNF-α、IL-6、IL-8、CRP水平的相关性。结果 治疗前两组TMAO、TNF-α、IL-6、IL-8及CRP水平无明显差异（Ps＞0.05）,治疗后两组上述指标均显著下降（Ps＜0.05）,其中益生菌组TMAO、TNF-α及CRP水平显著低于对照组（t=2.702,4.301,2.632;P=0.009,0.000,0.010）。治疗前两组患者大便中双歧杆菌载量无明显差异（P＞0.05）,治疗后益生菌组双歧杆菌载量显著提高（t=4.382,P=0.000）,且显著高于对照组（P＜0.05）。Pearson相关性分析显示,双歧杆菌载量与TMAO、TNF-α水平存在显著负相关（r＝-0.706,-0.427;P＝0.000,0.017）。结论 益生菌可有效改善SCAD患者TMAO水平,其与TMAO、TNF-α水平呈显著负相关。     

女性2型糖尿病患者尿液细菌分布及其与血清IL-6的相关性

目的检测女性2型糖尿病(T2DM)患者尿液细菌多样性特征,分析其与白细胞介素-6(IL-6)水平的相关性。方法选择2016年1月至2019年6月于本院诊治的女性T2DM患者60例作为T2DM组。选择同期于本院行尿液细菌检测的健康女性60例作为健康组。收集两组对象尿液样本,采用细菌DNA测序法对样本内细菌16S rRNA-cDNA高可变区进行测序,比较两组对象尿液细菌分布特征。采用ELISA法测定血清IL-6水平,根据IL-6检出情况分为IL-6组和非IL-6组,比较两组对象尿液细菌的组成情况及其与IL-6的关系。结果 T2DM组患者尿液微生物多样性、Shannon指数、谱系多样性、菌种丰富度指数均低于健康组(均P0.05)。共发现35个细菌门,其中T2DM组33个,健康组35个。T2DM组患者相对丰度较多的细菌为变形菌门(50.77%)、拟杆菌门(21.62%)和厚壁菌门(14.46%)。健康组相对丰度较多的细菌为变形菌门(54.49%)、拟杆菌门(22.81%)和厚壁菌门(10.02%)。T2DM组患者尿液中绿弯菌门、硝化螺旋菌门、疣微菌门相对丰度均低于健康组(均P0.05),其他菌门差异无统计学意义(均P0.05)。共发现438个细菌属,其中T2DM组438个,健康组421个。T2DM组和健康组共有30个菌属水平差异有统计学意义(均P0.05)。IL-6组和非IL-6组患者尿液微生物多样性、Shannon指数、谱系多样性、菌种丰富度指数比较差异均无统计学意义(均P0.05)。多元回归分析显示,共有15种细菌属与血清IL-6水平有线性相关关系。结论女性T2DM患者尿液菌群紊乱且与IL-6互为影响,应关注患者尿液菌群和膀胱炎症情况。     

Residue-level determinants of angiopoietin-2 interactions with its receptor Tie2

We combined computational and experimental methods to interrogate the binding determinants of angiopoietin-2 (Ang2) to its receptor tyrosine kinase (RTK) Tie2—a central signaling system in angiogenesis, inflammation, and tumorigenesis. We used physics-based electrostatic and surface-area calculations to identify the subset of interfacial Ang2 and Tie2 residues that can affect binding directly. Using random and site-directed mutagenesis and yeast surface display (YSD), we validated these predictions and identified additional Ang2 positions that affected receptor binding. We then used burial-based calculations to classify the larger set of Ang2 residues that are buried in the Ang2 core, whose mutations can perturb the Ang2 structure and thereby affect interactions with Tie2 indirectly. Our analysis showed that the Ang2-Tie2 interface is dominated by nonpolar contributions, with only three Ang2 and two Tie2 residues that contribute electrostatically to intermolecular interactions. Individual interfacial residues contributed only moderately to binding, suggesting that engineering of this interface will require multiple mutations to reach major effects. Conversely, substitutions in substantially buried Ang2 residues were more prevalent in our experimental screen, reduced binding substantially, and are therefore more likely to have a deleterious effect that might contribute to oncogenesis. Computational analysis of additional RTK-ligand complexes, c-Kit-SCF and M-CSF-c-FMS, and comparison to previous YSD results, further show the utility of our combined methodology.     

Follistatin-like protein 1: a serum biochemical marker reflecting the severity of joint damage in patients with osteoarthritis

Introduction  

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been implicated in arthritis pathogenesis in a mouse model. The aim of this study is to detect FSTL1 expression and to further assess its potential utility as a biomarker of joint damage in osteoarthritis (OA) patients.     

Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial cells and recently discovered progenitor cells, named as endothelial progenitor cells (EPCs). Up to now, many attempts have been made to understand the dynamic balance of pro- and anti-angiogenic factors on EPCs on different milieu. It has been accepted that Ang-1, -2 and Tie-1, -2 signaling play a key role on angiogenesis pathways in endothelial lineage cells. In the current experiment, the angiogenic/angio-modulatory potency of Ang-1 and -2 was investigated on isolated EPCs. Freshly isolated EPCs were exposed to different concentrations of Ang-1 and -2 (25 and 50?ng/ml) over a course of 7 and 14 days. Corroborating to our results, a superior effect of Ang-1 on angiogenic properties, including an increased concentration of vascular endothelial growth factor, in vitro tubulogenesis, EPC migratory, Tie-2 expression and clonogenicity, was determined. A large amount of positive mature endothelium markers was achieved in EPCs being-exposed to Ang-1 peptide. Nonetheless, the number of CD133 positive cells increased in the presence of Ang-2. Collectively, we conclude that Ang-1 potentially induces functional and mature vascular-like behavior in EPCs more than Ang-2.     

Regulation of the expression balance of angiopoietin-1 and angiopoietin-2 by Shh and FGF-2

Sonic hedgehog (Shh) is a typical morphogen to regulate epithelial–mesenchymal interactions during embryonic development. Shh is also an indirect angiogenic agent upregulating other angiogenic factors, including angiopoietin-1 (Ang-1). Recent studies revealed that angiogenesis induced by Shh is characterized by distinct large-diameter vessels with less branching. Ang-1 promotes blood vessel maturation, and angiopoietin-2 (Ang-2) counteracts Ang-1 activity and regulates vascular branching. Thus, we hypothesized that Shh-induced angiogenesis is affected by expression of Ang-1 and Ang-2, and we investigated the regulatory system of angiopoietins by Shh in vitro. Shh enhanced Ang-1 expression but did not enhance vascular endothelial growth factor in fibroblasts. The upregulation of Ang-1 expression by Shh was significantly decreased by fibroblast growth factor-2 (FGF-2), a potent angiogenic factor. Furthermore, FGF-2 increased the expression of Ang-2 in endothelial cells. These findings suggest that Shh and FGF-2 regulate the expression balance of vascular morphogens Ang-1 and Ang-2 and are involved in angiogenesis.     

Increased serum pancreatic polypeptide and serum gastrin secretion in patients with functional dyspepsia: correlation to the shape of the duodenal loop

Simultaneous measurement of food-stimulated serum pancreatic polypeptide and serum gastrin was carried out in 18 patients with functional dyspepsia and correlated to the shape of the duodenal loop. Significantly higher serum concentrations of pancreatic polypeptide and gastrin were encountered in patients with an abnormal shape of the duodenal loop compared to patients with a normal shape. Although no cause could be given to the phenomenon it may be taken into account when evaluating hormone profiles in patients with functional dyspepsia.     

Relationship of serum adiponectin and resistin levels with the severity of liver fibrosis in patients with chronic hepatitis B

BackgroundRecent research has closely linked adipocytokines to liver inflammation and fibrosis progression in patients with non-alcoholic liver disease. This study aimed to determine the relationship of serum adiponectin and resistin levels with the severity of liver fibrosis in patients with chronic hepatitis B (CHB), depending on the duration of antiviral therapy.MethodsThe cross-sectional study included 75 patients with CHB divided into two groups: the T1 group (undergoing antiviral therapy for up to 2 years) and the T2 group (undergoing antiviral therapy over 2 years). The control group consisted of 40 healthy people. Serum concentrations of adiponectin and resistin were estimated with the ELISA method, while the degree of liver fibrosis was determined using FIB-4 and APRI score.ResultsThere were no statistically significant differences in the mean serum adiponectin levels in relation to the duration of antiviral therapy. Higher values of serum resistin concentration were confirmed in patients of the T1 group compared to healthy controls (p=0.001) and to the T2 group (p=0.031). The mean level of serum resistin concentration was significantly higher in the group of patients with a higher FIB-4 score (9.12±3.39 vs 5.58±3.36 ng/mL, p=0.001) and higher APRI score (17.45±3.96 ng/mL vs 4.82±1.11 ng/mL, p=0.001). A positive correlation was found between serum resistin levels and the degree of liver fibrosis (p<0.001). There was no significant difference between mean serum adiponectin levels according to the values of FIB-4 and APRI scores.ConclusionsProgression of liver fibrosis estimated by FIB4 and APRI scores as well as the length of antiviral treatment had a significant effect on serum resistin values in CHB patients on antiviral therapy.     

肛周脓肿和肛瘘患者的病原菌分布及其与血清MMP 2、IL 17A水平的相关性

目的 分析肛周脓肿与肛瘘患者的病原菌分布及其与血清基质金属蛋白酶 2(MMP 2)、白细胞介素 17A(IL 17A)的相关性。 方法 收集2017年3月至2019年11月在我院收治的肛周脓肿和肛瘘患者共69例,分为肛周脓肿组(n=23)、肛瘘病程180 d组(n=9)。收集患者脓液或瘘管分泌物进行细菌培养,同时采集血清标本检测MMP 2、IL 17A水平,分析病原菌分布与MMP 2、IL 17A表达的相关性。 结果 69份标本中有66份标本培养出细菌,阳性率为95.65%(66/69)。共分离出68株细菌,其中有2份标本出现2种细菌同时生长,混合感染率为3.03%,其余64份标本均为单一细菌生长。68株细菌中革兰阴性菌58株(85.29%),革兰阳性菌8株(11.76%),真菌2株(2.94%)。各组患者血清MMP 2、IL 17A阳性率比较差异有统计学意义(均P0.05)。血清MMP 2与IL 17A水平呈正相关(r=0.325,P=0.009)。 结论 肛周脓肿与肛瘘患者以单一病原菌感染为主。患者血清MMP 2与IL 17A水平呈正相关。