Blood pressure control predicts plasma matrix metalloproteinase-9 in diabetes mellitus type II

Introduction

Matrix metalloproteinase-9 (MMP-9) plays an important role in extracellular and vascular remodelling. We aimed therefore to assess the role of blood pressure (BP) control on plasma MMP-9 in relation to the presence of diabetes mellitus (DM) type II.

Material and methods

Plasma MMP-9 was measured in 61 patients who were divided into two groups depending on their BP control as follows: 49 patients with uncontrolled arterial hypertension (AH) defined as BP values > 130/80 mm Hg and 12 patients with optimal blood pressure values. Plasma MMP-9 levels were measured with immunoassay at discharge. Group comparisons were made with the independent t-test, Mann-Whitney U-test and χ² test where appropriate. The associations of the variables with MMP-9 were investigated with linear regression analyses.

Results

The diabetics made up 34.4% of the investigated patients. Frequency of DM did not differ between the two BP groups (30.0% vs. 36.6%, p > 0.05). Plasma MMP-9 concentrations differed significantly between the diabetics vs. non-diabetics (median: 1.9 ng/ml, range: 1.0–7.3 vs. 1.4 ng/ml, range: 0.5–4.7, p < 0.05). Stratification across the categories of BP control showed a significant correlation between plasma MMP-9 and DM type II only in the uncontrolled BP group. The significance of that relationship disappeared in the group of patients with optimal BP control.

Conclusions

Plasma values of MMP-9 are raised in patients with DM type II. The results revealed the impact of the combination of uncontrolled AH and DM type II on vascular remodelling processes.     

Plasma adiponectin concentration and its association with metabolic syndrome in patients with heart failure

Purpose

Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients.

Materials and Methods

One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8±11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured.

Results

Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7±7.0 vs. 15.8±10.9 µg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E'' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012).

Conclusion

Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF.     

Microalbuminuria is Independently Associated with Arterial Stiffness and Vascular Inflammation but not with Carotid Intima-Media Thickness in Patients with Newly Diagnosed Type 2 Diabetes or Essential Hypertension

The association between microalbuminuria (MAU) and the indices of macrovascular complication in patients with newly diagnosed type 2 diabetes (D) or essential hypertension (H) was evaluated. Total 446 patients were classified into four groups according to the urinary albumin-to-creatinine ratio: MAU-D (n = 104), normoalbuminuria (NAU)-D (n = 114), MAU-H (n = 116), and NAU-H (n = 112). The indices of macrovascular complication including arterial stiffness evaluated by pulse-wave-velocity (PWV), carotid intima-media thickness (IMT), and vascular inflammation marked by high-sensitivity C-reactive protein (hsCRP) were assessed. PWV, IMT, and hsCRP were higher in patients with MAU than in those with NAU in both diabetes and hypertension groups. In both MAU-D and MAU-H groups, PWV and hsCRP levels were positively correlated with MAU level (MAU-D: r = 0.47, 0.41, MAU-H: r = 0.36, 0.62, respectively, P < 0.05). Additionally, PWV and hsCRP were independent factors predicting MAU (diabetes group: OR 1.85, 1.54, hypertension group: OR 1.38, 1.51, respectively, P < 0.001), but not IMT. MAU is independently associated with arterial stiffness and vascular inflammation but not with IMT in patients with newly diagnosed type 2 diabetes or essential hypertension, which emphasizes the importance of proactive clinical investigations for atherosclerotic complications in patients with MAU, even in newly diagnosed diabetes or hypertension.     

Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

AIM: To evaluate the association between the levels of homocysteine (Hcy), folate, vitamin B12 in human immunodeficiency virus (HIV)-infected patients who were treated with antiretroviral therapy (ART) or not treated with ART.METHODS: The PubMed and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes (1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and; (2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevMan (version 5.2) was employed for data synthesis.RESULTS: A total of 12 studies were included in outcome 1 (1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy (2.05 µmol/L; 95%CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations (-2.74 ng/mL; 95%CI: -5.18 to -0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis (1167 participants; 404 HIV-infected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to non-ART HIV subjects (4.13 µmol/L; 95%CI: 1.34 to 6.92, P < 0.01).CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection.     

Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of Disease in Patients with Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) increases patient mortality and medical expenditure, and a real-time and reliable method for the rapid diagnosis of VAP may help reduce fatal complications. Matrix metalloproteinases-9 (MMP-9) is considered significant in the pathogenesis of lung inflammation and infection. Therefore, we examined its relationship with the clinical course of VAP. This retrospective observational study recruited 30 healthy volunteers, 12 patients who used mechanical ventilation without the development of VAP (hereafter, patients without VAP), and 30 patients with a clinical diagnosis of VAP (hereafter, patients with VAP). The activity and level of plasma MMP-9 were determined through a gelatin zymography assay and ELISA. Our results report that both plasma MMP-9 activity and concentration were significantly elevated in the acute stage of patients with VAP when compared with control group and patients without VAP (p < 0.001). Subsequently, the plasma MMP-9 of patients with VAP decreased significantly after antibiotic treatment. Furthermore, plasma MMP-9 concentration was positively correlated with the clinical pulmonary infection score (r = 0.409, p = 0.007), WBCs (r = 0.620, p < 0.001), and neutrophils counts (r = 0.335, p = 0.035). In addition, plasma MMP-9 is an excellent tool for recognizing VAP when the cutoff level is set to 92.62 ng/mL (AUC = 0.863, 95% CI = 0.761 to 0.932). In conclusions, we concluded that MMP-9 levels play a role in the development of VAP and might have the potential to be applied in the development of VAP therapies.     

Changes in the activity of connective tissue matrix enzymes in the metabolic syndrome

Introduction

Early atherosclerotic changes in the endothelium associated with metabolic syndrome are generated with the participation of inflammatory cells, cytokines and enzymes of the extracellular matrix. The study is aimed at a comparison between the activity of inflammatory agents, tumour necrosis factor α (TNF-α) and the enzymes of the connective tissue matrix in the blood of healthy female patients as well as those suffering from the metabolic syndrome.

Material and methods

The examination included 35 women with metabolic syndrome (MS). The control group (C) comprised 35 healthy women. Lipidogram, C-reactive protein level (CRP), fasting glucose level (FGL), matrix metalloproteinase (MMP)-8 and -9 activity, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TNF-α levels in blood were determined.

Results

As compared with the control group, the level of inflammatory factors and the activity of extracellular matrix enzymes in the metabolic syndrome were statistically higher (p < 0.05) and concerned the following parameters: TNF-α (pg/ml): MS 6.59 ±3.18, C 4.78 ±2.91; CRP (mg/dl): MS 2.18 ±2.04, C 1,26 ±1.35; TIMP-1 (ng/ml): MS 265.5 ±2.9, C 205.4 ±72.6; MMP-9 (ng/ml): MS 198.2 ±138.6, C 138.6 ±116.1. Statistically significant correlations were also found between TIMP-1 and the following factors: BMI (R = 0.400, p < 0.001), waist/hip ratio (WHR) (R = 0.278, p < 0.05), waistline (R = 0.417, p < 0.001), FGL (R = 0.290, p < 0.05), HDL cholesterol (R = –0.253, p < 0.05) and triglycerides (R = 0.269, p < 0.05).There were positive correlations of MMP-9 with FGL (R = 0.446, p < 0.001) and waistline (R = 0.260, p < 0.05); MMP-8 with FGL (R = 0.308, p < 0.05); and CRP with BMI (R = 0.370, p < 0.01), WHR (R = 0.325, p < 0.01) and waistline (R = 0.368, p < 0.01).

Conclusions

Metabolic syndrome is connected with higher activity of cytokines (TNF-α), inflammatory markers (CRP) and matrix enzymes (MMP-9, MMP-8, TIMP-1).     

Effect of atorvastatin therapy on borderline vulnerable lesions in patients with acute coronary syndrome

Introduction

It is still controversial whether borderline lesions with a vulnerable plaque should be stented early or simply treated pharmacologically. No data exist concerning the potential effects of statin therapy on borderline vulnerable lesions in patients with acute coronary syndrome (ACS).

Material and methods

Fifty patients with ACS whose culprit lesions were classified as “borderline lesions” were enrolled. All patients were treated with atorvastatin (20 mg) for 12 months. Intravascular ultrasound (IVUS) was performed and matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and high-sensitive C-reactive protein (hsCRP) levels were measured at baseline and 12-month follow-up.

Results

At 12-month follow-up, we found: 1) IVUS revealed that minimal lumen cross-sectional area (CSA) increased but plaque/media (P&M) area and plaque burden decreased. A total of 25 soft plaques (50%) were transformed into fibrous plaques. 2) ApoB, MMP-9 and hsCRP levels decreased, but TIMP-1 level increased. 3) Stepwise multivariate linear regression analysis showed that the independent predictors for changes in P&M area/year were the decrease in MMP-9 and hsCRP levels.

Conclusions

Atorvastatin therapy stabilized borderline vulnerable plaques and reversed atherosclerosis progression in patients with ACS. Reversal of this progression was accompanied by a decrease in the levels of plasma MMP-9 and hsCRP. Changes in MMP-9 and hsCRP could predict vulnerable plaque stabilization.     

血浆同型半胱氨酸、超敏C反应蛋白与脑部大动脉粥样硬化性狭窄的相关性

目的探讨血浆总同型半胱氨酸（homocysteine，Hcy）、超敏C反应蛋白（high-sensitivity C-reactive protein，hs-CRP）水平与脑大动脉粥样硬化性（atherosclerosis，AS）狭窄的关系。方法对行数字减影全脑血管造影（digital subtraction angiography，DSA）的94例缺血性脑血管病患者进行分组，其中具有颅内外大动脉粥样硬化性狭窄（至少1支血管狭窄率〉50％）的68例患者为狭窄组，无狭窄或轻度狭窄（狭窄率≤50％）患者26例为对照组。对两组患者血浆总Hcy水平、hs-CRP及脑卒中的常规危险因素如年龄、性别、高血压、糖尿病、长期吸烟、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平等进行了分析。结果狭窄组血浆Hcy及hsCRP水平及升高的比例明显大于对照组；多元回归分析显示Hcy、hsCRP、高血压、糖尿病、吸烟与脑大动脉狭窄密切相关；血浆Hcy及hsCRP随大动脉硬化性狭窄程度加重而增高。结论血浆Hcy及hs-CRP水平升高与脑部动脉粥样硬化性狭窄密切相关，是脑大动脉粥样硬化性狭窄病变形成的危险因子。     

Chemopreventive Effect of Cousinia Shulabadensis Attar & Ghahraman Ethanol Extract

Matrix metalloprotainases (MMPs) play an important role in several pathologic processes such as malignancy in which they facilitate invasion and metastasis and can be targets for anticancer therapies. Here, in this study, we investigated the cytotoxicity effect of Cousinia shulabadensis Attar & Ghahraman extract as well as its impact on MMPs activity using a model of cell line (Fibrosarcoma-Wehi164). To assess anti-invasiveness potentials, a modified zymoanalysis method was used to measure MMP-2 and MMP-9 activities in the conditioned-media. The concentration necessary to produce 50% cell death was >80µg/ml for ethanol extract of Cousinia shulabadensis, while a 23 µg/ml concentration of the diclofenac sodium produced the same effect. The invasion of WEHI 164 cells was considerably inhibited at concentrations > 20 µg/ml by total plant extract. The total extract of the plant did not show high toxicity at all tested concentrations, but demonstrated significant inhibition of MMP activity in dose-response fashion.     

Expression of the reversion‐inducing cysteine‐rich protein with Kazal motifs and matrix metalloproteinase‐14 in neuroblastoma and the role in tumour metastasis

Neuroblastoma is the most common malignant tumour in infancy; the reversion-inducing cysteine-rich protein with Kazal motifs gene (RECK) is a tumour suppressor gene. Previous studies show that RECK inhibits tumour invasion and metastasis through negative regulation of the matrix metalloproteinase (MMP)-2, MMP-9 and MMP-14. Therefore, we wanted to detect the expression of RECK and MMP-14 in neuroblastomas to assess the correlation between the expression levels of these proteins, and to investigate the roles in the metastasis and development of the tumour. PV-6000 immunohistochemistry method was used to detect the expression levels of RECK and MMP-14 in 36 samples of neuroblastoma tissue. Samples from paraffin wax-embedded specimens and the complete clinicopathological data of 36 neuroblastoma and 10 ganglioneuroma patients were collected. The rate of expression of the RECK protein in the neuroblastoma was low (16.7%). Furthermore, it reduced with the increase in the invasive depth and distant metastasis (P=0.015; P<0.05). The rate of expression of the MMP-14 protein in the neuroblastoma was high (58.3%) and increased with the increase in the extent of invasive depth and distant metastasis (P=0.002; P<0.05). The expression of the RECK protein correlated negatively with that of MMP-14 (r =−0.418; P<0.05). Low levels of the RECK protein are expressed in the neuroblastoma, while the MMP-14 protein is expressed at high levels. The RECK and MMP-14 proteins may serve as markers in the estimation of the extent of metastasis and dissemination of the neuroblastoma.     

Association of Plasma Levels of Resistin with Subcutaneous Fat Mass and Markers of Inflammation but not with Metabolic Determinants or Insulin Resistance

The aim of the present study was to investigate the relationship of plasma resistin levels with determinants of the metabolic syndrome (MetS) and anthropometric parameters in healthy Korean subjects. Plasma resistin levels were determined in 276 subjects. In subjects with MetS, the plasma resistin levels were not significantly increased compared to those without MetS (8.3±4.3 ng/mL vs. 8.5±3.6 ng/mL, respectively, P=0.84). In addition, the plasma resistin levels were not correlated with the body mass index, the waist circumference, homeostasis model assessment-insulin resistance (HOMA-IR), fasting plasma glucose or insulin levels. However, the plasma resistin levels were positively correlated with the abdominal subcutaneous fat (r=0.18, P<0.01) in all subjects and correlated with TNF α(r=-0.16, P<0.05) and hsCRP (r=0.15, P<0.05) in subjects without MetS but not with MetS. With multiple linear regression analysis, these linear associations remained to be significant. The results of this study show that plasma resistin levels in humans were not associated with markers of insulin resistance, obesity or other determinants of the MetS.     

Phosphorylation of AKT and Abdominal Aortic Aneurysm Formation

It is hypothesized that differential AKT phosphorylation between sexes is important in abdominal aortic aneurysm (AAA) formation. Male C57BL/6 mice undergoing elastase treatment showed a typical AAA phenotype (80% over baseline, P < 0.001) and significantly increased phosphorylated AKT-308 (p308) and total-AKT (T-AKT) at day 14 compared with female mice. Elastase-treated Raw cells produced increased p308 and significant amounts of matrix metalloproteinase 9 (MMP-9), and these effects were suppressed by {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 treatment, a known AKT inhibitor. Male and female rat aortic smooth muscle cells treated with elastase for 1, 6, or 24 hours demonstrated that the p308/T-AKT and AKT-Ser-473/T-AKT ratios peaked at 6 hours and were significantly higher in the elastase-treated cells compared with controls. Similarly, male cells had higher phosphorylated AKT/T-AKT levels than female cells. {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 also inhibited elastase-induced p308 formation more in female smooth muscle cells than in males, and the corresponding cell media had less pro–MMP-9. AKT siRNA significantly decreased secretion of pro–MMP-9, as well as pro–MMP-2 and active MMP-2 from elastase-treated male rat aortic smooth muscle cells. IHC of male mice AAA aortas showed increased p308, AKT-Ser-473, and T-AKT compared with female mice. Aortas from male AAA patients had a significantly higher p308/T-AKT ratio than female AAA tissues. These data suggest that AKT phosphorylation is important in the upstream regulation of MMP activity, and that differential phosphorylation may be important in sex differences in AAA.Abdominal aortic aneurysm (AAA) formation is accompanied by chronic inflammation of the aorta wall, with males four times more likely to develop the disease than females.¹ The activation of matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, has long been known to play a vital role in the destruction of the aortic wall, leading to AAA development.^2–6 However, little is known about upstream modulation of the MMPs during AAA formation. Activation of the molecules of the mitogen-activated protein (MAP) kinase pathways is often observed in inflammatory diseases, such as in AAAs. Two MAP kinases in particular, c-Jun N-terminal kinase (JNK) and extracellular signal–regulated kinase (ERK), have been shown to be important in the activation of MMP-2 and MMP-9 in the aorta.^7–10 In addition to the MAP kinase cascade, the molecules of the phosphoinositide 3-kinase pathway are also known to be important for the modulation of MMPs.^9,11–15 Moreover, AKT, a key molecule in the phosphoinositide 3-kinase pathway, has been shown to play an important role in sex-specific differences of various diseases.^16–20 The role of AKT in the modulation of MMPs has not been studied in AAA formation. Therefore, using an in vivo mouse model of AAA and human AAA tissue, as well as in vitro experiments with rat aortic smooth muscle cells (RASMCs) and Raw cells, we show increased phosphorylation of AKT in males compared with females.     

Association between Serotype-Specific Antibody Response and Serotype Characteristics in Patients with Pneumococcal Pneumonia,with Special Reference to Degree of Encapsulation and Invasive Potential

We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.     

Clinical Effects of Calcium Channel Blocker and Angiotensin Converting Enzyme Inhibitor on Endothelial Function and Arterial Stiffness in Patients with Angina Pectoris

To evaluate the effects of calcium channel blocker (CCB) and angiotensin converting enzyme inhibitor (ACEI) on endothelial function and arterial stiffness in stable angina pectoris (SAP), 87 patients with SAP (57.6±10.0 yr, 52 males) were divided into two groups; CCB group (group I: n=44, 57.9±9.7 yr, 23 males) vs. CCB plus ACEI group (group II: n=43, 57.2±10.5 yr, 29 males). Flow mediated vasodilation (FMD) of the brachial artery, pulse wave velocity (PWV), urinary albumin excretion (UAE), and high sensitivity C-reactive protein (hsCRP) were compared. FMD, PWV, UAE, and hsCRP were not different between the groups at baseline. After 6 months of treatment, FMD were significantly improved in group II (7.5±3.7 to 8.8±2.7%, p<0.001), but not in group I (7.9±2.7 to 8.2±2.8%, p=0.535). Brachial-ankle PWV were significantly improved in both groups (1,621.3±279.4 to 1,512.1±225.0 cm/sec in group I, p<0.001, 1,586.8±278.5 to 1,434.5±200.5 cm/sec in group II, p<0.001). However, heart-femoral PWV were significantly improved (1,025.7±145.1 to 946.2±112.2 cm/sec, p<0.001) and UAE were significantly decreased (20.19±29.92 to 13.03±16.42 mg/g Cr, p=0.019) in group II only. In conclusion, combination therapy with CCB and ACEI improves endothelial function, arterial stiffness, and UAE than CCB mono-therapy more effectively in patients with SAP.     

CD147 and MMP-9 expressions in type II/III adenocarcinoma of esophagogastric junction and their clinicopathological significances

Objectives: To investigate CD147 and matrix metalloproteinase-9 (MMP-9) expressions in type II/III adenocarcinoma of esophagogastric junction (AEG), and their clinicopathological significances. Methods: Seventy-four patients clinically and pathologically diagnosed with type II/III AEG were analyzed, each undergoing radical total gastrectomy and Roux-en-Y esophagojejunostomy. The avidin streptavidin-perosidase immunohistochemistry technique was used to detect CD147 and MMP-9 in type II/III AEGs and 20 para-tumor controls, and their correlations with clinicopathological data and their reciprocal relationship were then analyzed. Kaplan-Meier survival analysis was conducted to reveal their prognostic significances. SPSS 20.0 was used for data analysis. A difference was statistically significant with P < 0.05, and very significant with P < 0.01. Results: In type II/III AEG CD147 and MMP-9 were mainly expressed on cellular membrane of in tumor cell cytoplasm. MMP-9 expression was significantly stronger at tumor-stroma junction and front edge of invasion. Their positive rates were significantly higher in malignant tissues than para-tumor tissues (P < 0.01 for both). There existed a significant positive correlation between both expressions (P < 0.05). They were significantly more highly expressed in cancers with lymphatic metastasis (P < 0.01 for both), at TNM III/IV stages (P < 0.01 for both), and with poor differentiation grade (P < 0.05 for both). Higher CD147 and MMP-9 expression rates were correlated with inferior postsurgical survivals (P < 0.05 for both). Conclusions: CD147 and MMP-9 could be novel biomarkers for type II/III AEG, and potentially predict tumor progression and prognosis. They are worth further investigation.     

Elevated serum C-reactive protein as a prognostic marker in small cell lung cancer

Purpose

Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC).

Materials and Methods

The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox''s proportional hazards model.

Results

The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001).

Conclusion

High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.     

Effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model

Objective: Our objective is to explore the effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. Methods: 45 healthy male Wistar rats of clean grade were selected and divided into treatment group, model control group and blank control group. The rats in the treatment group and model control group received high-fat diet for 12 weeks and intraperitoneal injection of VD₃ to establish rat coronary atherosclerosis heart disease model. After modeling, the rats in the treatment group received gavage of 100 mg/(kg·d) curcimin, and the rats in the model control group and blank control group received gavage of 5 ml/(kg·d) distilled water, the intervention time was 4 weeks. After intervention, the rats were killed, and the hearts were dissected to obtain the samples of coronary artery. After embedding and frozen section, immunofluorescence method was used to detect the change of endarterium permeability in 3 groups, Western blot was used to detect matrix metalloproteinase-9 (MMP-9) and CD40L in coronary artery tissue, and enzyme linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α) and C reaction protein (CRP). Results: After modeling, compared with the blank control group, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-c) in the treatment group and model control group were significantly higher (P<0.05), however, high density lipoprotein cholesterin (HDL-c) was significantly lower. The pathological sections showed that there was lipidosis in rat coronary artery in treatment group and model control group, indicating that the modeling was successful. Immunofluorescence showed that there was only a little fluorochrome permeability in artery in blank control group, there was some fluorochrome permeability in artery in the treatment group and there was a lot of fluorochrome permeability in artery in the model control group. MMP-9 and CD40L in coronary artery tissue in the model control group were significantly higher than the treatment group (P<0.05), MMP-9 and CD40L in coronary artery tissue in the treatment group were significantly higher than the blank control group (P<0.05); serum TNF-α and CRP in the model control group were significantly higher than the treatment group (P<0.05), which were significantly higher in the treatment group than the blank control group (P<0.05). Conclusion: Rat coronary atherosclerosis heart disease model can be successfully established by feeding with high-fat diet and intraperitoneal injection of VD₃, the permeability of coronary artery in coronary heart disease rat model is significantly increased, which may be related to up-regulation of MMP-9, CD40L, TNF-α and CRP expression. Application of curcumin can inhibit expression of MMP-9, CD40L, TNF-α and CRP to improve the permeability of coronary artery.     

Inflammatory aortic aneurysm: possible manifestation of IgG4-related sclerosing disease

In this study, we investigate the hypothesis that IgG4-related autoimmune reaction is involved in the formation of inflammatory aortic aneurysms (IAA). We obtained 23 cases of IAA and 11 cases of atherosclerotic aortic aneurysms (AAA) as control group. We evaluated the expression of IgG4 in both IAA study cases and AAA control cases. In addition, immunohistochemical expression of C-Kit, CD21, CD34, S-100 protein, SMA, vimentin, p53, beta-catenin, and ALK-1, and EBV-LMP1 expression by in situ hybridization were performed only in IAA cases. Of the 23 patients, 20 were males and 3 were females (M: F ratio 6.7:1); age ranged from 43 to 81 years (average 64.3 years). Histologically, all 23 cases of IAA formed a mass that displayed inflammatory myofibroblastic tumor-like features. All lesions stained strongly and diffusely for vimentin and SMA (100%); 17 stained strongly and focally for CD34 (74%); and all were negative for C-Kit, CD21, S-100 protein, p53, beta-catenin, EBV-LMP1, and ALK-1. The numbers of infiltrating IgG4-positive plasma cells in IAA cases exceed that of AAA cases. Score 3 (>50 plasma cells/one 40X field) of IgG4-positive plasma cells was only seen in IAA cases (13/23, 57%), whereas none of the 11 cases of AAA showed score 3 IgG4-positive plasma cells (P=0.0018, Fischer‘s exact test). Our findings suggest that IAA may be an aortic manifestation of the IgG4-related sclerosing disease. The high number of positive plasma cells, >50 plasma cells/one 40X field is more specific for the IAA than for AAA; however, lesser number can be seen in both IAA and AAA patients.     

Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease

Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. Subjects and methods: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. Results: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (β = 0.392; t =2.226, P < 0.01). Conclusions: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.     

Correlation between matrix metalloproteinase-9 and endometriosis

Endometrial implantation is the major cause of endometriosis (EMS). Matrix metalloproteinase (MMPs) can degrade multiple extracellular matrix and has been postulated to be related with EMC occurrence. This study thus investigated serum and ascites levels of MMP-9 in EMS patients, in an attempt to discuss the correlation between MMP-9 and EMS. A total of 100 EMS patients, including eutopic endometrium and ectopic endometrium, were recruited in this study along with hysteromyoma patients as the control group. Peripheral blood and ascites samples were collected and tested for MMP-9 levels using gelatin zymogram and enzyme-linked immunosorbent assay (ELISA). In EMS patients, MMP-9 levels in serum and ascites were 6.24±0.53 mM and 38.57±4.93 mM, respectively. Both of them were significantly higher than those in control group (P<0.05). Eutopic endometrium group had higher MMP-9 levels compared to those in ectopic endometrium ones (P<0.05). With advancement of disease stage, EMS patients had progressively elevated MMP-9 levels (P<0.05). Patients at proliferative stage had higher MMP-9 secretion (P<0.05). In summary, site of endometrium, clinical stage and proliferative cycle were independent risk factors for EMS. The elevation of serum and ascites MMP-9 existed in EMS patients, of which those had ectopic endometrium, advanced stage and at proliferative stage had higher MMP-9 expression.