Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome Thu, 11 Feb 2016 16:15:19 +0000 http://www.hindawi.com/journals/dm/2016/3501373/ Acute respiratory distress syndrome (ARDS) is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS-associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care. Raiko Blondonnet, Jean-Michel Constantin, Vincent Sapin, and Matthieu Jabaudon Copyright © 2016 Raiko Blondonnet et al. All rights reserved. Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers Wed, 10 Feb 2016 13:12:35 +0000 http://www.hindawi.com/journals/dm/2016/5246217/ Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR). Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR. Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles. Zehra Jamil, Syeda Sadia Fatima, Khalid Ahmed, and Rabia Malik Copyright © 2016 Zehra Jamil et al. All rights reserved. Serum NT-proBNP Levels Are Not Related to Vitamin D Status in Young Patients with Congenital Heart Defects Wed, 03 Feb 2016 12:56:58 +0000 http://www.hindawi.com/journals/dm/2016/3970284/ Context. Hypovitaminosis D frequently occurs in early life and increases with age. Vitamin D has been suggested to influence cardiac performance and N-terminal-pro-type B natriuretic peptide (NT-proBNP) release in adults with heart failure. Objectives. To assess the vitamin D status and the impact of hypovitaminosis D on circulating NT-proBNP levels in young patients with congenital heart defects (CHD). Design and Patients. This cross-sectional study included the assessment of serum 25-hydroxyvitamin D (25OHD), parathyroid function markers, and NT-proBNP levels in a series of 230 young in-patients (117 females, 113 males; 6.4 (4.0–9.1) years (median, interquartile range)) with CHD. Results. Serum 25OHD levels <20 ng/mL were detected in 55.3% of patients. Optimal 25OHD levels (>30 ng/mL) occurred in 25% of patients. Serum 25OHD levels inversely correlated with age (, ) and height standard deviation score (, ). After correction for age, 25OHD negatively correlated with serum PTH levels (, ). PTH levels above the upper quartile (44 pg/mL) occurred in 32% of hypovitaminosis D patients. Serum NT-proBNP levels were not correlated with 25OHD and PTH levels. Conclusions. Half of the young CHD patients were diagnosed with 25OHD deficiency and a third of hypovitaminosis D patients experienced hyperparathyroidism. Nonetheless, serum NT-proBNP levels were not associated with hypovitaminosis D as well as hyperparathyroidism. E. Passeri, R. Rigolini, E. Costa, C. Verdelli, C. Arcidiacono, M. Carminati, and S. Corbetta Copyright © 2016 E. Passeri et al. All rights reserved. Anticardiac Antibodies in Patients with Chronic Pericardial Effusion Thu, 28 Jan 2016 13:30:31 +0000 http://www.hindawi.com/journals/dm/2016/9262741/ Objectives. Chronic pericardial effusion may be challenging in terms of diagnosis and treatment. Specific laboratory parameters predicting the frequency and severity of recurrences after initial drainage of pericardial effusion are lacking. Materials and Methods. Pericardial fluid (PF) and serum (SE) samples from 30 patients with chronic pericardial effusion (PE) who underwent pericardiocentesis and pericardioscopically guided pericardial biopsy were compared with SE and PF samples from 26 control patients. The levels of antimyolemmal (AMLA) and antifibrillary antibodies (AFA) in PE and SE from patients with pericardial effusion as well as PF and SE from controls were determined and compared. Results. AMLAs and AFAs in PF and SE were significantly higher in patients with chronic pericardial effusion than in the control group (AMLAs: = 0,01 for PF and = 0,004 for serum; AFAs: < 0,001 for PF and = 0,003 for serum). Patients with recurrence of PE within 3 months after pericardiocentesis had significantly higher levels of AMLAs in SE ( = 0,029) than patients without recurrence of PE. Conclusions. The identification of elevated anticardiac antibodies in PE and SE indicates increased immunological reactivity in chronic pericardial effusion. High titer serum levels of AMLAs also correlate with recurrence of pericardial effusion. Konstantinos Karatolios, Sabine Pankuweit, Anette Richter, Volker Ruppert, and Bernhard Maisch Copyright © 2016 Konstantinos Karatolios et al. All rights reserved. Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer Thu, 28 Jan 2016 07:58:44 +0000 http://www.hindawi.com/journals/dm/2016/9810383/ Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients. Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy. Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) () but not AC (). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy. Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy. Ursa Brown-Glaberman, Marilyn Marron, Pavani Chalasani, Robert Livingston, Maria Iannone, Jennifer Specht, and Alison T. Stopeck Copyright © 2016 Ursa Brown-Glaberman et al. All rights reserved. Laboratory Indicators of Aggrecan Turnover in Juvenile Idiopathic Arthritis Wed, 27 Jan 2016 14:09:26 +0000 http://www.hindawi.com/journals/dm/2016/7157169/ Objectives. Evaluation of chondroitin sulfate (CS), as an early marker of aggrecan degradation, and chondroitin sulfate 846 epitope (CS846), as a biomarker of CS synthesis, is an attempt at answering the question whether the therapy used in juvenile idiopathic arthritis (JIA) patients contributes to the normalization of biochemical changes in aggrecan. Methods and Results. Serum levels of CS and CS846 as well as catalase (CT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in erythrocyte were assessed in patients before and after treatment. In the course of JIA, aggrecan metabolism is disturbed, which is reflected by a decrease () in CS serum level and an increase () in CS846 concentration. Furthermore, increased () activities of CT, SOD, and GPx in untreated JIA patients were recorded. The anti-inflammatory treatment resulted in the normalization of CS846 level and SOD and GPx activities. In untreated patients, we have revealed a significant correlation between serum CS and CS846, CT, CRP, ESR, MMP-3, and ADAMTS-4, respectively, as well as between CS846 and CT, GPx, CRP, ESR, and TGF-β1, respectively. Conclusion. The observed changes of CS and CS846 in JIA patients indicate a further need of the therapy continuation aimed at protecting a patient from a possible disability. Katarzyna Winsz-Szczotka, Kornelia Kuźnik-Trocha, Katarzyna Komosińska-Vassev, Agnieszka Jura-Półtorak, and Krystyna Olczyk Copyright © 2016 Katarzyna Winsz-Szczotka et al. All rights reserved. Can the Neutrophil to Lymphocyte Ratio Be Used to Determine Gastric Cancer Treatment Outcomes? A Systematic Review and Meta-Analysis Tue, 26 Jan 2016 14:01:52 +0000 http://www.hindawi.com/journals/dm/2016/7862469/ The prognostic role of neutrophil to lymphocyte ratio (NLR) in gastric cancer remains controversial. We aimed to quantify the prognostic role of peripheral blood NLR in gastric cancer. A literature search was conducted in PubMed, EMBASE, and Cochrane databases. The results for overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). 19 studies with 5431 patients were eligible for final analysis. Elevated NLRs were associated with a significantly poor outcome for OS (HR = 1.98; 95% CI: 1.75–2.24, ) and PFS (HR = 1.58; 95% CI: 1.32–1.88, ) compared with patients who had normal NLRs. The NLR was higher for patients with late-stage compared with early-stage gastric cancer (OR = 2.76; 95% CI: 1.36–5.61, ). NLR lost its predictive role for patients with stage IV gastric cancer who received palliative surgery (HR = 1.73; 95% CI: 0.85–3.54, ). Our results also indicated that prognoses might be influenced by the NLR cutoff values. In conclusion, elevated pretreatment NLRs are associated with poor outcome for patients with gastric cancer. The ability to use the NLR to evaluate the status of patients may be used in the future for personalized cancer care. Jingxu Sun, Xiaowan Chen, Peng Gao, Yongxi Song, Xuanzhang Huang, Yuchong Yang, Junhua Zhao, Bin Ma, Xinghua Gao, and Zhenning Wang Copyright © 2016 Jingxu Sun et al. All rights reserved. The Relationship between Serum Endocan Levels and Depression in Alzheimer’s Disease Tue, 26 Jan 2016 13:40:39 +0000 http://www.hindawi.com/journals/dm/2016/8254675/ Objectives. Growing evidence suggests that angiogenic vascular factors may be involved in the pathogenic mechanism of Alzheimer’s disease (AD), and recently endocan has been proposed as an angiogenic biomarker. The aim of this study was to measure serum endocan levels according to the presence of depression in AD and to investigate the association among the serum endocan levels, cognitive function, and depression in these patients. Methods. Serum endocan levels were measured in 26 AD patients with depression, 29 AD patients without depression, and 29 healthy controls using an enzyme-linked immunosorbent assay kit. The Mini-Mental State Examination-Korean version (MMSE-KC) and the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) were used to evaluate cognitive function and depressive symptoms, respectively. Results. Serum endocan levels were significantly lower in AD patients with depression than in AD patients without depression or healthy controls. Serum endocan levels were negatively correlated with SGDS-K scores but not with MMSE-KC scores in AD patients. Conclusions. This study suggests that serum endocan levels might be associated with depression in AD. Future studies are needed to investigate the pathophysiological mechanisms or the role of endocan in AD with depression. Kyung Hee Yoon, So Yeon Kim, Yoo Sun Moon, Daeyoung Roh, Sang Kyu Lee, and Do Hoon Kim Copyright © 2016 Kyung Hee Yoon et al. All rights reserved. Molecular Biomarkers in Bladder Cancer: Novel Potential Indicators of Prognosis and Treatment Outcomes Tue, 26 Jan 2016 11:11:27 +0000 http://www.hindawi.com/journals/dm/2016/8205836/ Although many clinical and molecular markers for predicting outcomes in bladder cancer (BC) have been reported, their application in clinical practice remains unclear. Bladder carcinogenesis has two distinct molecular pathways that direct the development of BC. FGFR3 mutations are common in low-grade BC, while TP53 mutation or loss of RB1 is associated with muscle-invasive BC. However, no tissue-based gene markers confirmed by prospective large-scale trials in BC have been used in clinical practice. Micro-RNA analyses of BC tissue revealed that miR-145 and miR- function as tumor suppressors, whereas miR-183 and miR-17-5p function as oncogenic miRNAs. In liquid biopsy, circulating tumor cells (CTC), exosomes, or cell-free RNA is extracted from the peripheral blood samples of cancer patients to analyze cancer prognosis. It was reported that detection of CTC was associated with poor prognostic factors. However, application of liquid biopsy in BC treatment is yet to be explored. Although several cell-free RNAs, such as miR-497 in plasma or miR-214 in urine, could be promising novel circulating biomarkers, they are used only for diagnosing BC as the case that now stands. Here, we discuss the application of novel biomarkers in evaluating and measuring BC outcomes. Masayoshi Nagata, Satoru Muto, and Shigeo Horie Copyright © 2016 Masayoshi Nagata et al. All rights reserved. Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker Thu, 21 Jan 2016 13:06:29 +0000 http://www.hindawi.com/journals/dm/2016/7276502/ Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa. Sunga Choi, Ju Hyun Shin, Yu Ran Lee, Hee Kyoung Joo, Ki Hak Song, Yong Gil Na, Seok Jong Chang, Jae Sung Lim, and Byeong Hwa Jeon Copyright © 2016 Sunga Choi et al. All rights reserved. A Significant Statistical Advancement on the Predictive Values of ERCC1 Polymorphisms for Clinical Outcomes of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: An Updated Meta-Analysis Thu, 21 Jan 2016 07:46:49 +0000 http://www.hindawi.com/journals/dm/2016/7643981/ Background. There is no definitive conclusion so far on the predictive values of ERCC1 polymorphisms for clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We updated this meta-analysis with an expectation to obtain some statistical advancement on this issue. Methods. Relevant studies were identified by searching MEDLINE, EMBASE databases from inception to April 2015. Primary outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). All analyses were performed using the Review Manager version 5.3 and the Stata version 12.0. Results. A total of 33 studies including 5373 patients were identified. ERCC1 C118T and C8092A could predict both ORR and OS for platinum-based chemotherapy in Asian NSCLC patients (CT + TT versus CC, ORR: OR = 0.80, 95% CI = 0.67–0.94; OS: HR = 1.24, 95% CI = 1.01–1.53) (CA + AA versus CC, ORR: OR = 0.76, 95% CI = 0.60–0.96; OS: HR = 1.37, 95% CI = 1.06–1.75). Conclusions. Current evidence strongly indicated the prospect of ERCC1 C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients. However, the results should be interpreted with caution and large prospective studies are still required to further investigate these findings. Yali Han, Jie Liu, Meili Sun, Zongpu Zhang, Chuanyong Liu, and Yuping Sun Copyright © 2016 Yali Han et al. All rights reserved. Impact of S100A4 Expression on Clinicopathological Characteristics and Prognosis in Pancreatic Cancer: A Meta-Analysis Tue, 19 Jan 2016 14:05:19 +0000 http://www.hindawi.com/journals/dm/2016/8137378/ Background. The small Ca2+-binding protein S100A4 is identified as a metastasis-associated or metastasis-inducing protein in various types of cancer. The goal of this meta-analysis was to evaluate the relationship between S100A4 expression and clinicopathological characteristics and prognosis of patients with pancreatic cancer. Methods. A comprehensive literature search was carried out in the electronic databases PubMed and Chinese CNKI. Only the studies reporting the correlation between S100A4 expression and clinicopathological characteristics or overall survival (OS) of patients with pancreatic cancer are enrolled. Extracted data was analyzed using the RevMan 5.3 software to calculate the pooled relative risks (95% confidence interval, CI) for statistical analyses. Results. Seven studies including a total of 474 patients were enrolled into this meta-analysis. Negative expression of S100A4 was significantly associated with higher 3-year OS rate (RR = 3.92, 95% CI = 2.24–6.87, ), compared to S100A4-positive cases. Moreover, negative expression of S100A4 was also related to N0 stage for lymph node metastasis (RR = 2.15, 95% CI = 1.60–2.88, ). However, S100A4 expression was not significantly correlated with histological types and distant metastasis status. Conclusion. S100A4 expression represents a potential marker for lymph node metastasis of pancreatic cancer and a potential unfavorable factor for prognosis of patients with this disease. Shanshan Huang, Jiawei Zheng, Yufang Huang, Li Song, Yin Yin, Danzhen Ou, Shangxiang He, Xiong Chen, and Xuenong Ouyang Copyright © 2016 Shanshan Huang et al. All rights reserved. Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy Tue, 19 Jan 2016 12:43:54 +0000 http://www.hindawi.com/journals/dm/2016/7304538/ Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86); ] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51); ] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT. András Mihály Boros, Péter Perge, Zsigmond Jenei, Júlia Karády, Endre Zima, Levente Molnár, Dávid Becker, László Gellér, Zoltán Prohászka, Béla Merkely, and Gábor Széplaki Copyright © 2016 András Mihály Boros et al. All rights reserved. Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis Tue, 19 Jan 2016 08:51:49 +0000 http://www.hindawi.com/journals/dm/2016/7124186/ In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, ) placental insufficient pregnancies (resistance index 0.9 versus 0.63, ) () was compared to controls (). PAI-1 was increased (~10-fold, ) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (, ). The plasma’s angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels (, ). This association was attenuated by PAI-1 inhibiting antibody (). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies. Maxim D. Seferovic and Madhulika B. Gupta Copyright © 2016 Maxim D. Seferovic and Madhulika B. Gupta. All rights reserved. 1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats Mon, 18 Jan 2016 08:30:37 +0000 http://www.hindawi.com/journals/dm/2016/5803031/ Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). Methods. Forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups (, each). PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0) served as control. Mean pulmonary arterial pressure (mPAP) was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR) spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to discriminate different metabolic profiles. Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis. Conclusions. Metabolic dysfunction is involved in the development and progression of PAH. Taijie Lin, Jinping Gu, Caihua Huang, Suli Zheng, Xu Lin, Liangdi Xie, and Donghai Lin Copyright © 2016 Taijie Lin et al. All rights reserved. The Correlation of Serums CCL11, CCL17, CCL26, and CCL27 and Disease Severity in Patients with Urticaria Tue, 12 Jan 2016 14:02:51 +0000 http://www.hindawi.com/journals/dm/2016/1381760/ Background. Chemokines may be involved in the pathogenesis of urticaria, but their correlation with disease severity as well as eruption type is unclear. Objectives. The aim of this study was to explore the expression of chemokines in patients with urticaria. The association between disease severity and levels of chemokines was analysed. Materials and Methods. Serums CCL11, CCL17, CCL26, and CCL27, D-dimer, C-reactive protein, and total IgE were measured in 51 patients with urticaria and in 25 healthy control subjects. Results. Serums CCL11, CCL17, CCL26, and CCL27 were significantly higher in patients with urticaria than in the healthy controls (). Serum CCL27 strongly correlated with urticarial disease severity. Serums CCL17, CCL26, and CCL27 significantly correlated with D-dimer, while innercorrelations were noted among the chemokines. Conclusion. Our findings reveal that chemokines participate in the pathogenesis of urticaria. Further study in larger cohort is needed to testify whether they could be the biomarkers for predicting the severity of urticaria. Tao Lu, Xiaoyang Jiao, Mengya Si, Ping He, Jinbo Zou, Shuping Zhang, and Kang Zeng Copyright © 2016 Tao Lu et al. All rights reserved. Comparison of Serum MicroRNA21 and Tumor Markers in Diagnosis of Early Non-Small Cell Lung Cancer Mon, 11 Jan 2016 09:04:24 +0000 http://www.hindawi.com/journals/dm/2016/3823121/ Objective. To compare the clinical value of serum microRNA21 (miR21) and other tumor markers in early diagnosis of non-small cell lung cancer (NSCLC). Methods. Serums carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and miR21 were detected in 50 NSCLC cases and 60 healthy control individuals. Results. Average serums miR21, CEA, NSE, and CYFRA21-1 levels were significantly higher in the case group than in control group (). Analysis of areas under the receiver operating characteristic (ROC) curve (AUC) revealed that CEA had the highest diagnostic efficiency for NSCLC. Serums miR21 and CYFRA21-1 levels were significantly lower at TNM stages I-II than stages III-IV (). Further, logistic multivariate regression analysis showed that the incidence of early NSCLC (TNM stages I-II) was correlated with serums CYFRA21-1 (OR = 1.076) and miR21 (OR = 2.473) levels (). By AUC analysis, miR21 had the highest diagnostic efficiency for early NSCLC, and single or combined detection of serums CYFRA21-1 and miR21 levels showed improved diagnostic efficiency for joint detection of both markers. Conclusions. Serum miR21 could serve as an important marker for auxiliary diagnosis of early NSCLC, while joint detection of serums miR21 and CYFRA21-1 levels could improve diagnostic efficiency. Mingzhong Sun, Jiangxiang Song, Zhongwei Zhou, Rong Zhu, Hao Jin, Yuqiao Ji, Qiang Lu, and Huixiang Ju Copyright © 2016 Mingzhong Sun et al. All rights reserved. Circulating Glutamate and Taurine Levels Are Associated with the Generation of Reactive Oxygen Species in Paroxysmal Atrial Fibrillation Wed, 06 Jan 2016 13:59:27 +0000 http://www.hindawi.com/journals/dm/2016/7650976/ Atrial fibrillation (AF) is the most common cardiac arrhythmia, but its proarrhythmic mechanism remains to be elucidated. Glutamate (Glu) and taurine (Tau) are present in the myocardium at substantially higher concentrations than in the plasma, suggesting their active role in myocardium. Here, we tested the hypothesis that the metabolism of Glu and Tau is altered in association with the generation of reactive oxygen species (ROS) in patients with AF. Fifty patients with paroxysmal AF and 50 control subjects without a history of AF were consecutively enrolled. Circulating Glu and Tau levels were measured and correlations between Glu/Tau and ROS levels were examined. Glu/Tau content was significantly higher in patients with AF versus controls (Glu: versus  nmol/L; Tau: versus  nmol/L; mean ± standard deviation (SD), for both). Glu/Tau levels also showed an independent association with AF by multiple logistic regression analysis. Glu and Tau levels both showed significant positive associations with plasma hydroperoxide concentrations. These data suggest a novel pathophysiological role of Glu and Tau in association with ROS production in paroxysmal AF, providing new insights into the elevated amino acid content in cardiac disease. Shintaro Takano, Kousuke Fujibayashi, Nakaba Fujioka, Ei-ichi Ueno, Minoru Wakasa, Yasuyuki Kawai, and Kouji Kajinami Copyright © 2016 Shintaro Takano et al. All rights reserved. Systemic Inflammatory Response Based on Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker in Bladder Cancer Tue, 05 Jan 2016 07:27:23 +0000 http://www.hindawi.com/journals/dm/2016/8345286/ A growing body of evidence suggests that systemic inflammatory response (SIR) in the tumor microenvironment is closely related to poor oncologic outcomes in cancer patients. Over the past decade, several SIR-related hematological factors have been extensively investigated in an effort to risk-stratify cancer patients to improve treatment selection and to predict posttreatment survival outcomes in various types of cancers. In particular, one readily available marker of SIR is neutrophil-to-lymphocyte ratio (NLR), which can easily be measured on the basis of absolute neutrophils and absolute lymphocytes in a differential white blood cell count performed in the clinical setting. Many investigators have vigorously assessed NLR as a potential prognostic biomarker predicting pathological and survival outcomes in patients with urothelial carcinoma (UC) of the bladder. In this paper, we aim to present the prognostic role of NLR in patients with UC of the bladder through a thorough review of the literature. Hyung Suk Kim and Ja Hyeon Ku Copyright © 2016 Hyung Suk Kim and Ja Hyeon Ku. All rights reserved. Skin Autofluorescence in Systemic Sclerosis Is Related to the Disease and Vascular Damage: A Cross-Sectional Analytic Study of Comparative Groups Thu, 31 Dec 2015 07:30:27 +0000 http://www.hindawi.com/journals/dm/2015/837470/ Skin autofluorescence (AF), a relatively simple and time saving procedure, measures the accumulation of advanced glycation end (AGE) products. The importance in autoimmune rheumatic diseases, particularly, systemic sclerosis (SSc), has not been evaluated yet. The aim of our study was to examine the skin AF in the context of SSc patients and to analyse the relations between skin AF and other surrogate measures of atherosclerosis. Forty-seven patients with SSc and 47 healthy volunteers were included in this study as controls. Patients and controls underwent common carotid artery wall assessment, arterial stiffness and wave reflection measurements, laser Doppler measurements of capillary flow, assessment of endothelial function by brachial ultrasound, peripheral arterial tonometry, and AGE measurement by skin AF. Wall properties of the common carotid arteries and wave reflection measurements were not affected in these study patients compared to controls while measures reflecting small capillary flow were altered. The accumulation of AGE products measured by skin AF was more prominent in SSc patients than in healthy controls. AGE products’ score was significantly associated with carotid radial pulse wave velocity, intima media/carotid artery diameter ratio, capillary flow percentage change during occlusion, and the disease itself in a multivariate linear analysis model. Jolanta Dadoniene, Alma Cypiene, Ligita Ryliskyte, Rita Rugiene, Kristina Ryliškiene, and Aleksandras Laucevičius Copyright © 2015 Jolanta Dadoniene et al. All rights reserved. Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients Wed, 30 Dec 2015 08:10:46 +0000 http://www.hindawi.com/journals/dm/2015/351673/ Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54; ). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28; ) and additive (OR = 0.35; 95% CI: 0.17–0.71; ) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD. Omar I. Saadah, Noor Ahmad Shaik, Babajan Banaganapalli, Mohammed A. Salama, Sameer E. Al-Harthi, Jun Wang, Harbi A. Shawoosh, Sharifa A. Alghamdi, Yagoub Y. Bin-Taleb, Bakr H. Alhussaini, Ramu Elango, and Jumana Y. Al-Aama Copyright © 2015 Omar I. Saadah et al. All rights reserved. Krüppel-Like Factor 4 Inhibits the Transforming Growth Factor-β1-Promoted Epithelial-to-Mesenchymal Transition via Downregulating Plasminogen Activator Inhibitor-1 in Lung Epithelial Cells Tue, 29 Dec 2015 14:00:36 +0000 http://www.hindawi.com/journals/dm/2015/473742/ Transforming growth factor-β (TGF-β) signaling and TGF-β-promoted epithelial-to-mesenchymal transition (EMT) have been postulated to be the common pathway causing pulmonary fibrosis. However, the up- or downstreaming markers of TGF-β-induced EMT still need to be further recognized. In the present study, we investigated the regulation on Krüppel-like factor 4 (KLF-4) and plasminogen activator inhibitor-1 (PAI-1) by TGF-β in the murine lung epithelial LA-4 cells and then examined the regulation of both markers in the TGF-β-induced EMT by the PAI-1 knockdown or the KLF-4 overexpression. Our study indicated that TGF-β induced EMT in mouse LA-4 lung epithelial cells via reducing E-cadherin, while promoting Collagen I and α-SMA. And PAI-1 was upregulated, whereas KLF-4 was downregulated in the TGF-β-induced EMT model in LA-4 cells. Moreover, the siRNA-mediated PAI-1 knockdown inhibited the TGF-β-induced EMT, whereas the adenovirus-medicated KLF-4 overexpression markedly reduced the PAI-1 expression and inhibited the TGF-β-induced EMT in LA-4 cells. In conclusion, our study confirmed the downregulation of KLF-4 in the TGF-β-induced EMT in LA-4 cells. And the KLF-4 overexpression significantly reduced the TGF-β-induced PAI-1 and thus inhibited the TGF-β-induced EMT in mouse lung epithelial LA-4 cells. It implies that KLF-4 might be a promising target for effective control of the pulmonary fibrosis. Fang Sun and Ke Hu Copyright © 2015 Fang Sun and Ke Hu. All rights reserved. Reduced Histone H3 Acetylation in CD4+ T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults Tue, 29 Dec 2015 12:10:23 +0000 http://www.hindawi.com/journals/dm/2015/285125/ Aims. Latent autoimmune diabetes in adults (LADA) is the result of gene-environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4+ T lymphocytes from LADA patients. Methods. Blood CD4+ T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP) and histone deacetylases (HDAC1, HDAC2, and HDAC7) was measured by real-time polymerase chain reaction (RT-PCR). Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients’ CD4+ T lymphocytes (). Global level of H4 acetylation was not statistically different. Among LADA, CD4+ T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c) and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated. Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4+ T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications. Xi-yu Liu and Jiang-feng Xu Copyright © 2015 Xi-yu Liu and Jiang-feng Xu. All rights reserved. Postoperative CA19-9 Change Is a Useful Predictor of Intrahepatic Cholangiocarcinoma Survival following Liver Resection Tue, 29 Dec 2015 11:45:49 +0000 http://www.hindawi.com/journals/dm/2015/298985/ Background. To investigate the clinical significance of the perioperative CA19-9 change for predicting survival in intrahepatic cholangiocarcinoma (ICC) patients treated with surgical resection. Methods. We retrospectively reviewed the data from 74 ICC patients treated with surgical resection between April 2001 and July 2010. Perioperative CA19-9 (preoperative level, postoperative lowest level, and level at recurrence) levels were analyzed for patient distribution and survival. Results. Before surgery, there were 45 patients who had high preoperative CA19-9 levels (>37 U/mL) and 29 who had normal levels (≤37 U/mL). Of 45 patients with high CA19-9 levels, 34 had normalized CA19-9 levels after resection and 11 had persistently high levels. Of 34 patients with normalized CA19-9 levels, 18 showed recurrence. Of 29 patients with normal preoperative levels, 15 showed recurrence. Multivariate analysis presented that old age (hazard ratio [HR] = 3.881, ), persistently high postoperative CA19-9 level (HR = 4.41, ), perineural invasion (HR = 3.073, ), narrow resection margin (HR = 3.152, ), and lymph node metastasis (HR = 3.427, ) were significant independent risk factors for survival. Conclusions. Patients who have normalized CA19-9 levels postoperatively have longer survival outcomes. Therefore, normalized postoperative CA19-9 may be a useful clinical marker for ICC survival. Tae Yoo, Sang-Jae Park, Sung-Sik Han, Seong Hoon Kim, Seung Duk Lee, Young-Kyu Kim, Tae Hyun Kim, Sang Myung Woo, Woo Jin Lee, and Eun Kyung Hong Copyright © 2015 Tae Yoo et al. All rights reserved. Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns Mon, 28 Dec 2015 13:48:51 +0000 http://www.hindawi.com/journals/dm/2015/683087/ Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors. Ramón Gil Carreón-Burciaga, Rogelio González-González, Nelly Molina-Frechero, and Ronell Bologna-Molina Copyright © 2015 Ramón Gil Carreón-Burciaga et al. All rights reserved. Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia Sun, 27 Dec 2015 09:17:24 +0000 http://www.hindawi.com/journals/dm/2015/635670/ Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20–40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans’ syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions. W. Barcellini and B. Fattizzo Copyright © 2015 W. Barcellini and B. Fattizzo. All rights reserved. Significant Association of HLA-B Alleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study Thu, 24 Dec 2015 06:04:18 +0000 http://www.hindawi.com/journals/dm/2015/724935/ Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identify HLA-B alleles associated with autism in Thai population, we compared the frequency of HLA-B allele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology. HLA-13:02 (, OR = 2.229), HLA-38:02 (, OR = 1.628), HLA-44:03 (, OR = 1.645), and HLA-56:01 ( = 1.78 × 10−4, OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that the HLA-18:02 (, OR = 0.375) and HLA-46:12 (, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, four HLA-B genotypes of autistic patients had statistically significant relationship with control groups, consisting of HLA-39055801 (, OR = 24.697), HLA-27045801 (, OR = 6.872), HLA-35014403 (, OR = 30.269), and HLA-18014402 (P = 0.017, OR = 13.757). This is the first report on HLA-B associated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population. Apichaya Puangpetch, Pongwut Suwannarat, Montri Chamnanphol, Napatrupron Koomdee, Nattawat Ngamsamut, Penkhae Limsila, and Chonlaphat Sukasem Copyright © 2015 Apichaya Puangpetch et al. All rights reserved. Single Nucleotide Polymorphisms in P2X7 Gene Are Associated with Serum Immunoglobulin G Responses to Mycobacterium tuberculosis in Tuberculosis Patients Sun, 20 Dec 2015 12:54:20 +0000 http://www.hindawi.com/journals/dm/2015/671272/ Objective. Our study investigated the association between single nucleotide polymorphisms (SNPs) in P2X7 gene and serum immunoglobulin G (IgG) responses to mycobacterium tuberculosis (MTB) in TB patients. Methods. A total of 103 TB patients were enrolled as case group and 87 healthy individuals at same geographical region as control group. The SNP detection of 1513A>C and -762T>C was performed using PCR-RFLP, and the levels of serum IgG responses to MTB in all subjects were determined. Results. AC and CC of 1513A>C and TC and CC of -762T>C had higher frequencies in case group than in control group. TB patients carrying TC and CC of -762T>C had higher positive rate of IgG responses to MTB than those carrying TT. Additionally, patients carrying TC and CC of -762T>C had more MTB in sputum than those carrying TT. Conclusion. P2X7 SNPs, 1513A>C and -762T>C, may be associated with the susceptibility to tuberculosis, and -762T>C SNP may contribute to the development of MTB. The mutant genotype of -762T>C (TC and CC) may lower human capability of phagocytosis to MTB, leading to an increased morbidity of TB. Jiangdong Wu, Lijun Lu, Le Zhang, Yulei Ding, Fang Wu, Weize Zuo, and Wanjiang Zhang Copyright © 2015 Jiangdong Wu et al. All rights reserved. Correlation and Significance of Urinary Soluble Fas and Vascular Endothelial Growth Factor in Bladder Urothelial Cancer Sun, 20 Dec 2015 09:23:15 +0000 http://www.hindawi.com/journals/dm/2015/383509/ Aim. To investigate the correlation and significance between the urine soluble Fas (sFas) and vascular endothelial growth factor (VEGF) expression in patients with urothelial bladder carcinoma (UC). Methods. The level of sFas was measured by enzyme-linked immunosorbent assay (ELISA) and the expression of VEGF protein in UC surgical specimens was screened by immunohistochemical method. These data were analyzed through SPSS 13.0 software. Results. The urinary sFas levels were significantly higher in the patients with UC than in those without cancer (168.0 ng/mL ± 84.6 versus 56.2 ng/mL ± 37.0; < 0.05) and in the cases with a higher stage or grade than in those with a lower stage or grade (each < 0.05). They had a positive relationship between the expression of VEGF protein and the pathological stage or grade in UC tissues (each < 0.05). Spearman rank correlation test showed a significant correlation between sFas levels and VEGF expressions ( = 0.882, < 0.05). Conclusions. The effects of sFas and VEGF may play important roles together in the occurrence and progression of UC. Joint detection of urine sFas plus VEGF protein may provide valuable solutions to improve the diagnosis and treatment of UC. Huixiang Yang, Zhiyong Wang, Yong Guo, and Zemin Wang Copyright © 2015 Huixiang Yang et al. All rights reserved. Markers of Perioperative Bowel Complications in Colorectal Surgery Patients Tue, 15 Dec 2015 09:28:56 +0000 http://www.hindawi.com/journals/dm/2015/428535/ Colorectal cancer is a clinical condition whose treatment often involves intestinal resection. Such treatment frequently results in two major gastrointestinal complications after surgery: anastomotic leakage and prolonged ileus. Anastomotic leakage is a serious complication which, more often than not, is diagnosed late; to date, C-reactive protein is the only available diagnostic marker. A monocentric, prospective, open case-control study was performed in patients undergoing colorectal surgery. Intestinal fatty acid binding protein (i-FABP), citrulline, D-lactate, exhaled hydrogen, Escherichia coli genomic DNA, and ischemia modified albumin (IMA) were determined preoperatively, postoperatively, and on the following four consecutive days. Bacterial DNA was not detected in any sample, and i-FABP and D-lactate lacked any distinct potential to detect postoperative bowel complications. Exhaled breath hydrogen content showed unacceptably low sensitivity. However, citrulline turned out to be a specific marker for prolonged ileus on postoperative days 3-4. Using a cut-off value of 20 μmol/L, a sensitivity and specificity of ~75% was achieved on postoperative day 4. IMA was found to be an efficient predictor of anastomosis leak by calculating the difference between preoperative and postoperative values. This test had 100% sensitivity and 80% specificity and 100% negative and 20% positive predictive value. Radomír Hyšpler, Alena Tichá, Milan Kaška, Lenka Žaloudková, Lenka Plíšková, Eduard Havel, and Zdeněk Zadák Copyright © 2015 Radomír Hyšpler et al. All rights reserved.