Additional diagnostic value of the monocyte to red blood cell count ratio and the product of lymphocyte count and albumin concentration in lung cancer management.

The present study aimed to evaluate the potential of the monocyte to red blood cell count ratio (MRR), the neutrophil to red blood cell count ratio (NRR), the lymphocyte to red blood cell count ratio (LRR) and the product of lymphocyte count and albumin concentration (LA) for the diagnosis of lung cancer. The cases of 216 patients with newly diagnosed lung cancer and 184 healthy volunteers were retrospectively analysed. The MRR and NRR were found to be higher in patients with lung cancer compared with those in healthy controls, while the LRR and LA were lower. The receiver operating characteristic curve analysis revealed that of the four markers, the MRR and LA yielded a higher area under the curve (AUC) (MRR: AUC, 0.810; 95% CI, 0.768-0.847; and LA: AUC, 0.721; 95% CI, 0.674-0.764). The combination of MRR, LA, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) achieved the highest diagnostic value when compared with other single or combined markers (AUC, 0.882; 95% CI, 0.846-0.912; sensitivity, 81.9%; specificity, 81.0%). As the disease progressed, the MRR tended to increase, while LA exhibited a decreasing trend. Binary logistic regression analysis revealed an increase in the MRR, as well as in CEA and CYFRA21-1 concentrations, and a decrease in the LA, which could all be possible risk factors for lung cancer. Differences in the MRR and LA between patients with early stage (IA-IIIA) lung cancer and healthy controls were observed. Further analysis revealed that the MRR also exhibited the potential to detect early stage (IA-IIIA) lung cancer in the model. The present findings demonstrated that the MRR and LA may be used as auxiliary biomarkers for the diagnosis of lung cancer and could partly indicate disease progression.

Application of Monocyte-to-Albumin Ratio and Neutrophil Percentage-to-Hemoglobin Ratio on Distinguishing Non-Small Cell Lung Cancer Patients from Healthy Subjects.

Objective: This study aims at assessing the potential benefits of observation of monocyte-to-albumin ratio (MAR) and neutrophil percentage-to-hemoglobin ratio (NPHR) in the detection of non-small cell lung cancer (NSCLC). Methods: This study retrospectively involved 195 NSCLC patients and 204 healthy volunteers. The correlations between the clinicopathological characteristics of NSCLC and the two ratios including MAR and NPHR were assessed. The diagnostic efficiency of NSCLC patients by MAR and NPHR, alone or in combination with carcinoembryonic antigen (CEA), was assessed by receiver operating characteristic (ROC) curve. The risk factors for NSCLC were analyzed with binary logistic regression. Results: Compared to healthy controls, the levels of MAR and NPHR in NSCLC patients were elevated. MAR and NPHR were related to clinicopathologic characteristics and increased significantly along with the progression of NSCLC. The area under the curve (AUC) for 95% confidence interval (95% CI) of MAR and NPHR in the diagnosis of NSCLC was 0.812 (0.769-0.854) and 0.724 (0.675-0.774), respectively. The combination of MAR, NPHR, and CEA achieved the highest diagnostic utility compared to each individually or combined markers (AUC, 0.86; 95% CI, 0.824-0.896; sensitivity, 72.8%; specificity, 87.3%). Further analysis showed that MAR combined with NPHR presented the potential to detect early-stage (IA-IIB) NSCLC (AUC, 0.794; 95% CI, 0.743-0.845; sensitivity, 55.1%; specificity, 87.7%). The result indicated that MAR and NPHR might be risk factors for NSCLC. Conclusion: MAR and NPHR could be novel and effective auxiliary indexes in the detection of NSCLC, especially when combined with CEA.

miR­625­5p suppresses inflammatory responses by targeting AKT2 in human bronchial epithelial cells.

Asthma is a common chronic inflammatory airway disease; however, whether microRNAs (miRs) could be used in the treatment of asthma remains unclear. The aim of the present study was to investigate the role of miR­625­5p in the inflammatory response of human bronchial epithelial cells (HBECs). Inflammation in the HBEC line, 16HBEC, was induced using different concentrations of lipopolysaccharide (LPS), which demonstrated that 1 µg/ml LPS was an appropriate concentration for further experiments. The association between protein kinase B2 (AKT2) and miR­625­5p was verified using a luciferase reporter assay. LPS was added to 16HBECs following the administration of miR­625­5p mimics or miR­625­5p inhibitors, and cells with silenced or overexpressed AKT2 levels. miR­625­5p was expressed at a high level in LPS­activated 16HBECs. Overexpression of miR­625­5p inhibited interleukin (IL)­6 and tumor necrosis factor (TNF)­α secretion in 16HBECs. Inhibition of miR­625­5p enhanced LPS­induced IL­6 and TNF­α secretion. miR­625­5p negatively regulated the expression of AKT2 in 16HBECs. A dual­luciferase reporter assay system confirmed that miR­625­5p directly targeted the 3'untranslated region of AKT2. Transfection with a small interfering RNA against AKT2 inhibited inhibitor of κB phosphorylation. In brief, miR­625­5p may protect LPS­induced HBECs by targeting AKT2 and inhibiting the nuclear factor­κB signaling pathway. Therefore, miR­625­5p may function as an inhibitor of asthma airway inflammation in HBECs by targeting AKT2.

High-sensitivity C-reactive protein: a predicative marker in severe asthma.

BACKGROUND AND OBJECTIVE: Serum levels of high-sensitivity CRP (hs-CRP) are associated with asthma but the relationship between higher levels of hs-CRP and the degree of asthma severity remains unclear. This study investigated whether hs-CRP is associated with asthma severity as well as with other clinical indices of asthma activity (pulmonary function, total serum IgE, and peripheral blood eosinophil counts). METHODS: Levels of hs-CRP and clinical indices of asthma were determined among 177 control subjects and 281 asthmatic patients (84 intermittent, 30 mild, 63 moderate and 104 severe). RESULTS: The level of hs-CRP was examined as both a continuous variable and by quartiles (<0.23, 0.23-0.51, 0.51-1.42 and >or=1.42 mg/L) in the five groups. Compared with the first quartile of hs-CRP, patients with higher levels were at increased risk of severe asthma independently of other clinical indices (adjusted OR 3.49, 95% CI: 1.51-8.12 for the third quartile; adjusted OR 6.46, 95% CI: 2.85-16.62 for fourth quartile, respectively). CONCLUSIONS: These findings suggest that hs-CRP might be a sensitive marker for severe asthma.

Increased RhoGDI2 and peroxiredoxin 5 levels in asthmatic murine model of beta2-adrenoceptor desensitization: a proteomics approach.

BACKGROUND: Beta(2)-adrenoceptor (beta(2)AR) desensitization is a common problem in clinical practice. beta(2)AR desensitization proceeds by at least such three mechanisms as heterologous desensitization, homologous desensitization and a kind of agonist-induced rapid phosphorylation by a variety of serine/threonine kinases. It is not clear whether there are other mechanisms. This study aimed to investigate potential mechanisms of beta(2)AR desensitization. METHODS: Twenty-four BALB/c (6-8 weeks old) mice were divided into three groups, which is, group A, phosphate buffered saline (PBS)-treated; group B, ovalbumin (OVA)-induced; and group C, salbutamol-treated. Inflammatory cell counts, cytokine concentrations of bronchoalveolar lavage fluid (BALF), pathological sections, total serum IgE, airway responsiveness, membrane receptor numbers and total amount of beta(2)AR were observed. Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were established. Groups B and C were selected for two-dimensional gel electrophoresis (2DE) analysis so as to find key protein spots related to beta(2)AR desensitization. RESULTS: Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were verified by inflammatory cell count, cytokine concentration of BALF, serum IgE level, airway hyperreactivity measurement, radioligand receptor binding assay, Western blot analysis, and pathologic examination. Then the two groups (groups B and C) were subjected to 2DE. Two key protein spots associated with beta(2)AR desensitization, Rho GDP-dissociation inhibitor 2 (RhoGDI(2)) and peroxiredoxin 5, were found by comparative proteomics (2DE and mass spectrum analysis). CONCLUSION: Oxidative stress and small G protein regulators may play an important role in the process of beta(2)AR desensitization.

Expression of surface markers on peripheral CD4+CD25high T cells in patients with atopic asthma: role of inhaled corticosteroid.

BACKGROUND: CD4(+)CD25(+) regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules, particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), and transforming growth factor beta (TGF-beta), but little is known about the exact role of Tregs in the pathogenesis of asthma. This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects, and to investigate the effect of inhaled corticosteroid on them. METHODS: The expression of surface molecules on CD4(+)CD25(high) Tregs was detected by flow cytometry. The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro. Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay, respectively. RESULTS: Equivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects. Tregs preferentially expressed CTLA-4, GITR, toll-like receptor 4 (TLR4), latency-associated peptide (LAP/TGF-beta1), and forkhead box P3 (FOXP3). Patients with acute asthma had decreased numbers of CD4(+)CD25(high)LAP(+) T cells compared to healthy subjects and stable asthmatics. Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently. Furthermore, the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma, but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma. CONCLUSIONS: The results suggest that membrane-bound TGF-beta1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of asthma. Strategies targeting Tregs on their surface markers, especially TGF-beta1, are promising for future therapy of asthma.

Associations of Toll-like receptor 7 and 8 Polymorphisms with Asthma and Asthma-related Phenotypes in a Chinese Han Population.

Toll-like receptor (TLR) 7 and 8 mediate anti-virus immunity and are of particular relevance to asthma. However, very little information about genetic association on TLR7/8 and asthma are available. This study aimed to evaluate the effects of polymorphisms in TLR7 and 8 on asthma risk and asthma-related phenotypes in a Chinese Han population. We enrolled 462 unrelated adult asthmatic patients and 398 healthy volunteers. The genotypes of tagging single nucleotide polymorphisms (SNPs) in TLR7 and 8 genes were determined using multiplex SNaPshot SNP genotyping assay. We used case-control and case-only studies to assess any links with asthma and asthma-related phenotypes. There was no association between the variants in TLR7 and 8 and asthma susceptibility. However, our results revealed that the genetic variants in TLR7 and 8 were associated with asthma-related phenotypes, including eosinophil counts, serum immunoglobulin E levels, lung function, and asthma severity as well. Our study suggests that TLR7 and 8 polymorphisms may play a considerable role in the pathogenesis of asthma. It will help in better understanding the pathogenesis of asthma and development of more effective strategies for asthma prevention, prediction, and therapy.