Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Prevalence and Prognostic Implications of Vitamin D Deficiency in Chronic Kidney Disease Thu, 26 Mar 2015 12:01:02 +0000 http://www.hindawi.com/journals/dm/2015/868961/ Vitamin D is an important nutrient involved in bone mineral metabolism, and vitamin D status is reflected by serum total 25-hydroxyvitamin D (25[OH]D) concentrations. Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD), and nutritional vitamin D supplementation decreases elevated parathyroid hormone concentrations in subgroups of these patients. Furthermore, vitamin D is supposed to have pleiotropic effects on various diseases such as cardiovascular diseases, malignancies, infectious diseases, diabetes, and autoimmune diseases. Indeed, there is cumulative evidence showing the associations of low vitamin D with the development and progression of CKD, cardiovascular complication, and high mortality. Recently, genetic polymorphisms in vitamin D-binding protein have received great attention because they largely affect bioavailable 25(OH)D concentrations. This finding suggests that the serum total 25(OH)D concentrations would not be comparable among different gene polymorphisms and thus may be inappropriate as an index of vitamin D status. This finding may refute the conventional definition of vitamin D status based solely on serum total 25(OH)D concentrations. Yoshitsugu Obi, Takayuki Hamano, and Yoshitaka Isaka Copyright © 2015 Yoshitsugu Obi et al. All rights reserved. miR-34a Inhibits Proliferation and Invasion of Bladder Cancer Cells by Targeting Orphan Nuclear Receptor HNF4G Mon, 23 Mar 2015 13:50:27 +0000 http://www.hindawi.com/journals/dm/2015/879254/ miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3′-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells. Huaibin Sun, Jun Tian, Wanhua Xian, Tingting Xie, and Xiangdong Yang Copyright © 2015 Huaibin Sun et al. All rights reserved. Circulating Soluble Neuropilin-1 in Patients with Early Cervical Cancer and Cervical Intraepithelial Neoplasia Can Be Used as a Valuable Diagnostic Biomarker Thu, 19 Mar 2015 13:45:22 +0000 http://www.hindawi.com/journals/dm/2015/506428/ Objective. To investigate soluble neuropilin-1 (sNRP-1) in circulating and NRP-1 protein in cervical tissues from patients with cervical cancer or cervical intraepithelial neoplasia (CIN). Methods. sNRP-1 was measured in 64 preoperative patients and 20 controls. NRP-1 protein in cervical tissue was detected in 56 patients and 20 controls. Results. Both sNRP-1 and NRP-1 proteins were correlated with stage. sNRP-1 presented a high diagnostic ability of cervical cancer and CIN, with a sensitivity of 70.97% and a specificity of 73.68%. Conclusions. sNRP-1 in circulating can serve as a possible valuable diagnostic biomarker for cervical cancer and CIN. Shouhua Yang, Henghui Cheng, Zaiju Huang, Xiaoling Wang, Yinglu Wan, Jing Cai, and Zehua Wang Copyright © 2015 Shouhua Yang et al. All rights reserved. The Diagnostic Accuracy of HE4 in Lung Cancer: A Meta-Analysis Thu, 19 Mar 2015 12:23:39 +0000 http://www.hindawi.com/journals/dm/2015/352670/ The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68–0.75), SPE 0.85 (95% CI: 0.81–0.88), PLR 4.68 (95% CI: 3.23–6.78), NLR 0.31 (95% CI: 0.24–0.39), and DOR 17.14 (95% CI: 9.72–30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future. Daye Cheng, Ying Sun, and Hu He Copyright © 2015 Daye Cheng et al. All rights reserved. Assessment of Cell-Cycle Arrest Biomarkers to Predict Early and Delayed Acute Kidney Injury Wed, 18 Mar 2015 15:40:07 +0000 http://www.hindawi.com/journals/dm/2015/158658/ Purpose. To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels. Methods. We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression. Results. Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34–0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels () but AKI was not (). Sepsis was independently associated with higher NGAL () and cystatin-C () levels. Conclusions. Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor. Max Bell, Anders Larsson, Per Venge, Rinaldo Bellomo, and Johan Mårtensson Copyright © 2015 Max Bell et al. All rights reserved. Twenty-Four-Hour Urine Osmolality as a Physiological Index of Adequate Water Intake Wed, 18 Mar 2015 06:18:16 +0000 http://www.hindawi.com/journals/dm/2015/231063/ While associations exist between water, hydration, and disease risk, research quantifying the dose-response effect of water on health is limited. Thus, the water intake necessary to maintain optimal hydration from a physiological and health standpoint remains unclear. The aim of this analysis was to derive a 24 h urine osmolality (UOsm) threshold that would provide an index of “optimal hydration,” sufficient to compensate water losses and also be biologically significant relative to the risk of disease. Ninety-five adults (31.5 ± 4.3 years, 23.2 ± 2.7 kg·m−2) collected 24 h urine, provided morning blood samples, and completed food and fluid intake diaries over 3 consecutive weekdays. A UOsm threshold was derived using 3 approaches, taking into account European dietary reference values for water; total fluid intake, and urine volumes associated with reduced risk for lithiasis and chronic kidney disease and plasma vasopressin concentration. The aggregate of these approaches suggest that a 24 h urine osmolality ≤500 mOsm·kg−1 may be a simple indicator of optimal hydration, representing a total daily fluid intake adequate to compensate for daily losses, ensure urinary output sufficient to reduce the risk of urolithiasis and renal function decline, and avoid elevated plasma vasopressin concentrations mediating the increased antidiuretic effort. Erica T. Perrier, Inmaculada Buendia-Jimenez, Mariacristina Vecchio, Lawrence E. Armstrong, Ivan Tack, and Alexis Klein Copyright © 2015 Erica T. Perrier et al. All rights reserved. Immunohistochemical Expression of Survivin and Its Relationship with Cell Apoptosis and Proliferation in Ameloblastomas Wed, 18 Mar 2015 06:15:06 +0000 http://www.hindawi.com/journals/dm/2015/301781/ Ameloblastoma behavior is related to the potential of tumor cells to inhibit apoptosis and to initiate a proliferative phase. This study was performed to compare the immunoexpression of Survivin with Bcl-2, Bax, and Ki-67 and to associate them with the histopathological type of each variant of ameloblastoma. Material and Methods. Using the World Health Organization (WHO) criteria for ameloblastoma, 110 cases were selected. The cases were classified as solid/multicystic and unicystic ameloblastomas. Cellular counts of cytoplasmic immunoexpression were assessed for cytoplasmic Survivin, Bcl-2, and Bax, while the nuclear immunoexpression of Survivin and Ki-67 was assessed using label index. Results. Cytoplasmic Survivin and Bcl-2 showed higher percentages of immunoexpression in solid multicystic ameloblastomas compared to unicystic ameloblastomas (). Bax, Ki-67, and nuclear Survivin were expressed in higher percentages in unicystic ameloblastomas. Conclusions. Cytoplasmic Survivin and Bcl-2 immunoexpression levels were elevated in relation to Bax immunoexpression, suggesting aggressive ameloblastoma behavior, while Ki-67 and nuclear Survivin immunoexpression may be associated with the type of tumor morphology that influences cellular counts or with the greater capacity for cellular proliferation and tumor growth. Rogelio González-González, Nelly Molina-Frechero, Pablo Damian-Matsumura, Sirced Salazar-Rodriguez, and Ronell Bologna-Molina Copyright © 2015 Rogelio González-González et al. All rights reserved. Comment on “System Accuracy Evaluation of the GlucoRx Nexus Voice TD-4280 Blood Glucose Monitoring System” Tue, 17 Mar 2015 13:30:25 +0000 http://www.hindawi.com/journals/dm/2015/538785/ Nilesh Nathwani Copyright © 2015 Nilesh Nathwani. All rights reserved. Biomarkers of Lung Injury in Cardiothoracic Surgery Tue, 17 Mar 2015 08:48:48 +0000 http://www.hindawi.com/journals/dm/2015/472360/ Diagnosis of pulmonary dysfunction is currently almost entirely based on a vast series of physiological changes, but comprehensive research is focused on determining biomarkers for early diagnosis of pulmonary dysfunction. Here we discuss the use of biomarkers of lung injury in cardiothoracic surgery and their ability to detect subtle pulmonary dysfunction in the perioperative period. Degranulation products of neutrophils are often used as biomarker since they have detrimental effects on the pulmonary tissue by themselves. However, these substances are not lung specific. Lung epithelium specific proteins offer more specificity and slowly find their way into clinical studies. Gerwin Erik Engels and Willem van Oeveren Copyright © 2015 Gerwin Erik Engels and Willem van Oeveren. All rights reserved. Vascular Effects of Advanced Glycation End-Products: Content of Immunohistochemically Detected AGEs in Radial Artery Samples as a Predictor for Arterial Calcification and Cardiovascular Risk in Asymptomatic Patients with Chronic Kidney Disease Tue, 17 Mar 2015 08:19:15 +0000 http://www.hindawi.com/journals/dm/2015/153978/ Objectives. Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters. Materials and Methods. The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified. Results. Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient’s age. Conclusions. The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients. Katarzyna Janda, Marcin Krzanowski, Mariusz Gajda, Paulina Dumnicka, Ewa Jasek, Danuta Fedak, Agata Pietrzycka, Marek Kuźniewski, Jan A. Litwin, and Władysław Sułowicz Copyright © 2015 Katarzyna Janda et al. All rights reserved. Serum Creatinine Level: A Supplemental Index to Distinguish Duchenne Muscular Dystrophy from Becker Muscular Dystrophy Tue, 17 Mar 2015 07:26:52 +0000 http://www.hindawi.com/journals/dm/2015/141856/ Background. To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. Methods. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Results. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation and partial correlation analysis after adjustment for age, height, and weight (; both ). Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations and in Becker muscular dystrophy (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7, and 9 yr (all ). After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients . Conclusions. Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice. Huili Zhang, Yuling Zhu, Yiming Sun, Yingyin Liang, Yaqin Li, Yu Zhang, Langhui Deng, Xingxuan Wen, and Cheng Zhang Copyright © 2015 Huili Zhang et al. All rights reserved. The Apolipoprotein B/Apolipoprotein A-I Ratio as a Potential Marker of Plasma Atherogenicity Tue, 17 Mar 2015 07:18:31 +0000 http://www.hindawi.com/journals/dm/2015/591454/ Background. The apolipoprotein (apo) B/apoA-I ratio represents the balance between apoB-rich atherogenic particles and apoA-I-rich antiatherogenic particles, and this ratio is considered to be a marker of cardiovascular risk. Although many studies have demonstrated the importance of the apoB/apoA-I ratio in predicting the presence or absence of cardiovascular disease, less is known about apoB/apoA-I ratio as a marker of plasma atherogenicity. Methods. A total of 157 normolipidemic men aged 20–59 years were included in the study. The plasma levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apoA-I, apoB, and apoE were determined after a 12 h fasting period. Results. The median of the apoB/apoA-I ratio in the studied normolipidemic subjects was 0.52, with values ranging from 0.19 to 2.60. The percentage of subjects with the apoB/apoA-I ratio exceeding 0.9 (the accepted risk value of cardiovascular disease) was 19.1%. The subjects with apoB/apoA-I>0.9 were characterized by higher TG levels and atherogenic index of plasma (AIP) and lower values of ratio of low-density lipoprotein cholesterol (LDL-C) to apoB (LDL-C/apoB) and apoE levels compared with men with apoB/apoA-I<0.9. Conclusion. Despite normolipidemia, the subjects with the unfavorable apoB/apoA-I ratio had more atherogenic lipid profile. Anastasiya M. Kaneva, Natalya N. Potolitsyna, Evgeny R. Bojko, and Jon Ø. Odland Copyright © 2015 Anastasiya M. Kaneva et al. All rights reserved. Procalcitonin Levels in Gram-Positive, Gram-Negative, and Fungal Bloodstream Infections Tue, 17 Mar 2015 07:16:12 +0000 http://www.hindawi.com/journals/dm/2015/701480/ Procalcitonin (PCT) can discriminate bacterial from viral systemic infections and true bacteremia from contaminated blood cultures. The aim of this study was to evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative, and fungal bloodstream infections. A total of 1,949 samples from patients with suspected bloodstream infections were included in the study. Median PCT value in Gram-negative (13.8 ng/mL, interquartile range (IQR) 3.4–44.1) bacteremias was significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6–7.6) or fungal (0.5 ng/mL, IQR 0.4–1) infections (). Receiver operating characteristic analysis showed an area under the curve (AUC) for PCT of 0.765 (95% CI 0.725–0.805, ) in discriminating Gram-negatives from Gram-positives at the best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919–0.969, ) in discriminating Gram-negatives from fungi at the best cut-off of 1.6 ng/mL. Additional results showed a significant difference in median PCT values between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1 ng/mL, IQR 5.9–48.5 versus 3.5 ng/mL, IQR 0.8–21.5; ). This study suggests that PCT may be of value to distinguish Gram-negative from Gram-positive and fungal bloodstream infections. Nevertheless, its utility to predict different microorganisms needs to be assessed in further studies. Christian Leli, Marta Ferranti, Amedeo Moretti, Zainab Salim Al Dhahab, Elio Cenci, and Antonella Mencacci Copyright © 2015 Christian Leli et al. All rights reserved. Serum Metabolites as Potential Biomarkers for Diagnosis of Knee Osteoarthritis Mon, 16 Mar 2015 12:29:05 +0000 http://www.hindawi.com/journals/dm/2015/684794/ Knee osteoarthritis (OA) is a highly prevalent chronic degenerative joint disease that mainly affects the elderly population. The aim of this study was to investigate serum signature metabolites as potential biomarkers for early diagnosis of knee OA. Global serum metabolic profiles of 40 patients with knee OA and 20 healthy controls (HC) were analyzed by ultra-performance liquid chromatography coupled to mass spectrometry. An OA-specific metabolic profile was established that can clearly discriminate patients with OA from HCs. Fourteen metabolites that are involved in the metabolism of amino acids, purine, energy, glycolysis, fatty acids, and lipids were significantly altered in patients with OA compared to HCs. These metabolites could be potentially used as biomarkers for the diagnosis of knee OA. Qingmeng Zhang, Heng Li, Zhendong Zhang, Fan Yang, and Jiying Chen Copyright © 2015 Qingmeng Zhang et al. All rights reserved. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study Sun, 15 Mar 2015 12:46:56 +0000 http://www.hindawi.com/journals/dm/2015/795801/ The Glasgow Prognostic Score (GPS) is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT), white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males), 81 (23.8%) died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67) for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9), , AUC 0.69) and significantly improved the GPS to a combined AUC of 0.74 (). Considering all investigated biomarkers, the AUC increased to 0.76 (). The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials. Anna Christina Rast, Alexander Kutz, Susan Felder, Lukas Faessler, Deborah Steiner, Svenja Laukemann, Sebastian Haubitz, Andreas Huber, Ulrich Buergi, Antoinette Conca, Barbara Reutlinger, Beat Mueller, Mario Bargetzi, and Philipp Schuetz Copyright © 2015 Anna Christina Rast et al. All rights reserved. Measurement of Cytokines and Adhesion Molecules in the First 72 Hours after Severe Trauma: Association with Severity and Outcome Wed, 11 Mar 2015 12:26:30 +0000 http://www.hindawi.com/journals/dm/2015/747036/ Introduction. Severity and outcome assessments are crucial in trauma. Our aim was to describe the role of a group of cytokines (TNFα, IL-6, IL-10, and HMGB-1) and ICAM-1 as severity and outcome assessment tools and their kinetics in the first 72 h after severe trauma. Materials and Methods. Authors designed a prospective cohort study of severe polytrauma patients (ISS > 15) in a level 1 Trauma Centre. Cytokines and ICAM-1 levels and Th1/Th2 ratios were assessed at admission, 24, 48, and 72 h. SIRS, SIRS with hypoperfusion, and shock were identified. Outcomes considered were ICU admission, ARDS, MODS, and death. Results. Ninety-nine patients were enrolled (median ISS: 29 and age 31). There was an early release of pro- and anti-inflammatory mediators with higher values at admission (except for ICAM-1). On admission, IL-6 was associated with ISS, IL-10 with SIRS with hypoperfusion, and HMGB-1 with shock. Several cytokines were associated with outcomes, especially IL-6 and IL-10 at 72 h with MODS and death. Low TNFα/IL-10 and IL-6/IL-10 ratios at 24 and 72 h were associated with MODS and death. Conclusions. Pro- and anti-inflammatory responses occur simultaneously and earlier after injury. Cytokines may be useful for outcome assessment, especially IL-6 and IL-10. Low Th1/Th2 ratio at 24 to 72 h is associated with MODS and death. António Sousa, Frederico Raposo, Sara Fonseca, Luís Valente, Filipe Duarte, Moura Gonçalves, Diana Tuna, and José-Artur Paiva Copyright © 2015 António Sousa et al. All rights reserved. MHC Class I Chain-Related Gene A Diversity in Patients with Cutaneous Malignant Melanoma from Southeastern Spain Mon, 09 Mar 2015 09:50:33 +0000 http://www.hindawi.com/journals/dm/2015/831864/ A limited number of studies have been performed so far on the polymorphism in the transmembrane region (exon 5) of the major histocompatibility complex class I chain-related gene A (MICA) in patients with melanoma. However, the influence of MICA polymorphism in extracellular domains (exons 2, 3, and 4) has not been investigated on melanoma disease. This study aims to characterize the influence of extracellular MICA polymorphism, and its previously described linkage disequilibrium with HLA-B locus, on patients with cutaneous melanoma from southeastern Spain. For this purpose, MICA and HLA-B genotyping was performed in 233 patients and 200 ethnically matched controls by luminex technology. Patients were classified according to the presence of methionine or valine at codon 129 of MICA gene. We found a high frequency of MICA*009 in melanoma patients compared with controls (, Pc = 0.03). Our results also showed an association between MICA*009 and HLA-B*51 alleles in both patients and controls. This association was stronger in patients than controls (). However, a multivariate logistic regression model showed that neither MICA*009 nor the combination MICA*009/HLA-B*51 was associated with melanoma susceptibility. No relationship was observed between MICA-129 dimorphism and melanoma nor when MICA polymorphism was evaluated according to clinical findings at diagnosis. José Antonio Campillo, Ruth López-Hernández, Helios Martínez-Banaclocha, José Miguel Bolarín, Lourdes Gimeno, Anna Mrowiec, Manuela López, Beatriz Las Heras, Alfredo Minguela, Maria Rosa Moya-Quiles, Isabel Legáz, José Francisco Frías-Iniesta, Ana María García-Alonso, María Rocío Álvarez-López, Jorge Antonio Martínez-Escribano, and Manuel Muro Copyright © 2015 José Antonio Campillo et al. All rights reserved. The Effect of Depression on Serum VEGF Level in Alzheimer’s Disease Sun, 08 Mar 2015 14:14:16 +0000 http://www.hindawi.com/journals/dm/2015/742612/ Objective. Growing evidence suggests that angiogenesis might represent a new pathogenic mechanism involved in the progression of Alzheimer’s disease (AD). Among angiogenic cytokines, vascular endothelial growth factor (VEGF) levels in AD patients have been evaluated, but the results are controversial among studies. We investigated serum levels of VEGF in AD patients with depression, AD patients without depression, and the controls, respectively. The aim of this study is to elucidate the relationship between VEGF, depression, and cognitive impairment in AD. Methods. The CDR (Clinical Dementia Rating), MMSE-KC (the Mini-Mental Status Examination-Korean version), and SGDS-K (the Korean version of the Geriatric Depression Scale-Short Form) were measured in the subjects. Serum VEGF levels were measured in 24 AD patients with depression, 25 AD patients without depression, and 26 controls, using an enzyme-linked immunosorbent assay kit. Results. Serum VEGF levels in AD patients with depression were significantly higher than AD patients without depression or the control. A correlation was observed between VEGF and scores on SGDS-K, but no correlation was detected between VEGF and MMSE-KC scores. Conclusion. Serum VEGF levels in AD patients with depression were higher than those without depression. Depression might be associated with changes in serum levels of VEGF in AD patients. JaeHoon Jung, SoYeon Kim, KyungHee Yoon, YooSun Moon, Daeyoung Roh, SangKyu Lee, KyungChan Choi, JunSub Jung, and DoHoon Kim Copyright © 2015 JaeHoon Jung et al. All rights reserved. Resistin, Visfatin, Adiponectin, and Leptin: Risk of Breast Cancer in Pre- and Postmenopausal Saudi Females and Their Possible Diagnostic and Predictive Implications as Novel Biomarkers Sun, 08 Mar 2015 12:36:19 +0000 http://www.hindawi.com/journals/dm/2015/253519/ The mechanisms of obesity-induced breast carcinogenesis are not clear. One hypothesis is that high levels of adipokines could promote breast cancer (BC) development. The aim of this study was to investigate the correlation of resistin, visfatin, adiponectin, and leptin with BC risk in pre- and postmenopausal females. A total of 82 BC newly diagnosed and histologically confirmed patients and 68 age and BMI matched healthy controls were enrolled. Both groups were subdivided into post- and premenopausal subgroups. Resistin, visfatin, adiponectin, and leptin were measured by ELISA. There were significantly higher levels of leptin, resistin, and visfatin in postmenopausal BC patients than their respective controls. Only in postmenopausal subgroups, leptin, resistin, and visfatin levels were positively correlated with TNM staging, tumor size, lymph node (LN) metastasis, and histological grading. In postmenopausal females, multivariate logistic regression analysis revealed that adiponectin, leptin, visfatin, and resistin were risk factors for BC. Our results suggested that serum resistin, leptin, adiponectin, and visfatin levels as risk factors for postmenopausal BC may provide a potential link with clinicopathological features and are promising to be novel biomarkers for postmenopausal BC. Adel M. A. Assiri, Hala F. M. Kamel, and Mohamed F. R. Hassanien Copyright © 2015 Adel M. A. Assiri et al. All rights reserved. Difference in the Prognostic Significance of N-Terminal Pro-B-Type Natriuretic Peptide between Cardioembolic and Noncardioembolic Ischemic Strokes Thu, 05 Mar 2015 13:59:38 +0000 http://www.hindawi.com/journals/dm/2015/597570/ Background and Aim. Because B-type natriuretic peptide is a powerful predictor of heart failure, its capability to predict a fatal outcome in stroke might be limited to the cardioembolic stroke subtype. In this study, we attempt to ascertain the difference in the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) between cardioembolic and noncardioembolic stroke subgroups. Methods. 410 acute stroke patients were included. According to the presence of a cardioembolic source (CES), there were 221 patients with CES and 189 patients without CES. Logistic regression analysis was performed to ascertain the association between NT-proBNP and 6-month mortality/functional outcome in each group. Results. The mean age of our patients was 67.2 years (range, 18–97 years). NT-proBNP was a multivariate independent predictor of mortality in the CES group alone, whereas it was only a univariate predictor of 6-month mortality in the total patient and non-CES groups with its association disappearing in the multivariate model. In addition, it was only a univariate predictor of good functional outcome in all of the groups. Conclusions. Our data suggest that NT-proBNP can more reliably predict 6-month mortality in patients with cardioembolic stroke than in patients with other stroke subtypes. Seung-Jae Lee, Dong-Geun Lee, Dal-Soo Lim, Sukkeun Hong, and Jin-Sik Park Copyright © 2015 Seung-Jae Lee et al. All rights reserved. Blockade of Aquaporin 1 Inhibits Proliferation, Motility, and Metastatic Potential of Mesothelioma In Vitro but not in an In Vivo Model Wed, 04 Mar 2015 14:04:11 +0000 http://www.hindawi.com/journals/dm/2015/286719/ Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM. Methods. Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies. Results. Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours. Conclusions. Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo. Sonja Klebe, Kim Griggs, Yuen Cheng, Jack Driml, Douglas W. Henderson, and Glen Reid Copyright © 2015 Sonja Klebe et al. All rights reserved. Capillary Deposition of Complement C4d and C3d in Chinese Renal Allograft Biopsies Wed, 04 Mar 2015 08:12:33 +0000 http://www.hindawi.com/journals/dm/2015/397613/ Background. C3d is a product of both the classic and the alternative complement cascades; however, few studies have addressed the role of C3d in renal biopsies and its relationship with long-term graft survival rate is not very clear. Methods. 94 patients with biopsy-proven acute rejection episodes were included in the study. We investigated the associations between histological findings, clinical examinations, and outcome. Results. The overall prevalence for C4dPTC and C3dPTC was 42.6% and 29.8%. There was a significant association between C3dPTC and C4dPTC (). C3dPTC and C4dPTC were related with histological types ( and , resp.). The long-term survival rate for C4dPTC positive transplants was lower than that of C4dPTC negative transplants, but it was not statistic significant in our study (). The survival rate of C3dPTC positive group was much lower than the negative group (). Patients with double positives for C4dPTC and C3dPTC exhibited the lowest survival rate significantly different from those of the C3dPTC only and C4dPTC only groups ( and ). Conclusions. This longitudinal cohort study has demonstrated that C3d deposition in the PTC was closely related to renal dysfunction and pathological changes. Rong Lv, Wei Zhang, Fei Han, Guangjun Liu, Wenqing Xie, and Jianghua Chen Copyright © 2015 Rong Lv et al. All rights reserved. Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners Tue, 03 Mar 2015 14:14:08 +0000 http://www.hindawi.com/journals/dm/2015/806418/ High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy), improved exercise metabolism (lactate threshold), and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases. M. J. Laye, M. B. Nielsen, L. S. Hansen, T. Knudsen, and B. K. Pedersen Copyright © 2015 M. J. Laye et al. All rights reserved. α-2-Macroglobulin in Saliva Is Associated with Glycemic Control in Patients with Type 2 Diabetes Mellitus Tue, 03 Mar 2015 11:59:56 +0000 http://www.hindawi.com/journals/dm/2015/128653/ Background. Subjects with type 2 diabetes mellitus (DM2) require an adequate glycemic control to avoid diabetic complications. Currently, saliva biomarkers are used as a diagnostic tool and can be indicative of the degree of progression and control of various diseases. Several studies indicate that α-2-macroglobulin levels are elevated in diabetic patients. Methods. 120 subjects with DM2 were enrolled and classified into two groups according to their glycemic control (percentage of glycated hemoglobin-A1c (HbA1c), <7% adequate glycemic control group; >7% inadequate glycemic control group). The relationship between α-2-macroglobulin levels from saliva samples and HbA1c was subsequently evaluated. Results. We found a positive correlation between α-2-macroglobulin and HbA1c ( and ). Area under the receivers operating characteristic (ROC) curve of α-2-macroglobulin indicated a positive discrimination threshold of α-2-macroglobulin (AUC = 0.903, CI 95%: 0.847–0.959, ) to diagnose glycemic control. Conclusions. Our data strongly suggest that the level of saliva α-2-macroglobulin is an indicator for the degree of glycemic control in diabetic patients and represents a promising alternative method to evaluate this parameter. Juan Pablo Aitken, Carolina Ortiz, Irene Morales-Bozo, Gonzalo Rojas-Alcayaga, Mauricio Baeza, Caroll Beltran, and Alejandro Escobar Copyright © 2015 Juan Pablo Aitken et al. All rights reserved. 3-Nitrotyrosine Modified Proteins in Atherosclerosis Sun, 01 Mar 2015 09:12:04 +0000 http://www.hindawi.com/journals/dm/2015/708282/ Cardiovascular disease is the leading cause of premature death worldwide, and atherosclerosis is the main contributor. Lipid-laden macrophages, known as foam cells, accumulate in the subendothelial space of the lesion area and contribute to consolidate a chronic inflammatory environment where oxygen and nitrogen derived oxidants are released. Oxidatively modified lipids and proteins are present both in plasma as well as atherosclerotic lesions. A relevant oxidative posttranslational protein modification is the addition of a nitro group to the hydroxyphenyl ring of tyrosine residues, mediated by nitric oxide derived oxidants. Nitrotyrosine modified proteins were found in the lesion and also in plasma from atherosclerotic patients. Despite the fact of the low yield of nitration, immunogenic, proatherogenic, and prothrombotic properties acquired by 3-nitrotyrosine modified proteins are in agreement with epidemiological studies showing a significant correlation between the level of nitration found in plasma proteins and the prevalence of cardiovascular disease, supporting the usefulness of this biomarker to predict the outcome and to take appropriate therapeutic decisions in atherosclerotic disease. Leonor Thomson Copyright © 2015 Leonor Thomson. All rights reserved. BRCA Genetic Screening in Middle Eastern and North African: Mutational Spectrum and Founder BRCA1 Mutation (c.798_799delTT) in North African Sat, 28 Feb 2015 14:16:58 +0000 http://www.hindawi.com/journals/dm/2015/194293/ Background. The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC) has not yet been thoroughly investigated in MENA. Methods. To establish the knowledge about BRCA1 mutations and their correlation with the clinical aspect in diagnosed cases of HBOC in MENA populations. A systematic review of studies examining BRCA1 in BC women in Cyprus, Jordan, Egypt, Lebanon, Morocco, Algeria, and Tunisia was conducted. Results. Thirteen relevant references were identified, including ten studies which performed DNA sequencing of all BRCA1 exons. For the latter, 31 mutations were detected in 57 of the 547 patients ascertained. Familial history of BC was present in 388 (71%) patients, of whom 50 were mutation carriers. c.798_799delTT was identified in 11 North African families, accounting for 22% of total identified BRCA1 mutations, suggesting a founder allele. A broad spectrum of other mutations including c.68_69delAG, c.181T>G, c.5095C>T, and c.5266dupC, as well as sequence of unclassified variants and polymorphisms, was also detected. Conclusion. The knowledge of genetic structure of BRCA1 in MENA should contribute to the assessment of the necessity of preventive programs for mutation carriers and clinical management. The high prevalence of BC and the presence of frequent mutations of the BRCA1 gene emphasize the need for improving screening programs and individual testing/counseling. Abdelilah Laraqui, Nancy Uhrhammer, Hicham EL Rhaffouli, Yassine Sekhsokh, Idriss Lahlou-Amine, Tahar Bajjou, Farida Hilali, Jamila El Baghdadi, Abderrahmane Al Bouzidi, Youssef Bakri, Said Amzazi, and Yves-Jean Bignon Copyright © 2015 Abdelilah Laraqui et al. All rights reserved. Effect of Periodontal Surgery on Osteoprotegerin Levels in Gingival Crevicular Fluid, Saliva, and Gingival Tissues of Chronic Periodontitis Patients Sat, 28 Feb 2015 10:00:27 +0000 http://www.hindawi.com/journals/dm/2015/341259/ Objectives. This study was undertaken to investigate the OPG profiles in gingival crevicular fluid (GCF), saliva, and gingival tissues of chronic periodontitis (CP) patients in response to open flap debridement (OFD). Subjects and Methods. The study included 30 subjects divided into 2 groups: 20 CP patients and 10 periodontally healthy subjects. Plaque index, gingival index, pocket depth, and clinical attachment level measurements were recorded for all subjects. GCF, salivary, and gingival samples were collected from all 30 subjects at baseline and 3 and 6 month after OFD from the 20 CP patients. GCF and salivary OPG levels were assessed by ELISA assay, while OPG expression in gingival tissues was examined by immunohistochemistry. Results. GCF, salivary and gingival OPG profiles were significantly higher in control subjects compared to CP patients at baseline (). Within CP group, OPG levels in GCF, saliva, and gingival samples showed a significant increase at 3 and 6 months after OFD () compared to baseline. Although OPG values increased significantly in gingival samples and insignificantly in saliva after 3 months compared to 6 months, yet GCF levels were significantly decreased. Conclusions. OPG might be considered as a diagnostic and prognostic biomarker of periodontal bone destruction. This trial is registered with NCT02160613. Sandy H. S. Hassan, Mahmoud I. El-Refai, Noha A. Ghallab, Rehab Fawzy Kasem, and Olfat G. Shaker Copyright © 2015 Sandy H. S. Hassan et al. All rights reserved. Secernin-1 Contributes to Colon Cancer Progression through Enhancing Matrix Metalloproteinase-2/9 Exocytosis Thu, 26 Feb 2015 12:36:38 +0000 http://www.hindawi.com/journals/dm/2015/230703/ Emerging evidence shows that exocytosis plays a key role in tumor development and metastasis. Secernin-1 (SCRN1) is a novel regulator of exocytosis. Our previous work identified SCRN1 as a tumor-associated gene by bioinformatics analysis of transcriptomes. In this study, we demonstrated the aberrant overexpression of SCRN1 at mRNA and protein level in colon cancer. We also revealed that overexpression of SCRN1 was significantly associated with the tumor development and poor prognosis. Experiments in vitro validated that SCRN1 may promote cancer cell proliferation and secretion of matrix metalloproteinase-2/9 (MMP-2/9) proteins to accelerate tumor progression. Shengtao Lin, Tao Jiang, Yang Yu, Huamei Tang, Su Lu, Zhihai Peng, and Junwei Fan Copyright © 2015 Shengtao Lin et al. All rights reserved. Identification of Endogenous Controls for Analyzing Serum Exosomal miRNA in Patients with Hepatitis B or Hepatocellular Carcinoma Thu, 26 Feb 2015 07:14:10 +0000 http://www.hindawi.com/journals/dm/2015/893594/ Serum exosomal microRNAs (miRNAs) have received considerable attention as potential biomarkers for diagnosing cancer. The canonical technique for measuring miRNA transcript levels is reverse transcription quantitative polymerase chain reaction (RT-qPCR). One prerequisite for validating RT-qPCR data is proper normalization with respect to stably expressed endogenous reference genes. However, genes that meet all of the criteria of a control gene for exosomal miRNAs have not yet been identified. To find out the control gene for exosomal miRNAs, we evaluated the expression stability of 11 well-known reference genes in circulating exosomes. In this study, we found that the combination of miR-221, miR-191, let-7a, miR-181a, and miR-26a can be an optimal gene reference set for normalizing the expression of liver-specific miRNAs. This combination enhanced the robustness of the relative quantification analyses. These findings highlight the importance of validating reference genes before quantifying target miRNAs. Furthermore, our findings will improve studies that monitor hepatitis progression and will aid in the discovery of noninvasive biomarkers to diagnose early stage HCC. Yi Li, Liqun Zhang, Fei Liu, Guiming Xiang, Dongneng Jiang, and Xiaoyun Pu Copyright © 2015 Yi Li et al. All rights reserved. Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility Wed, 25 Feb 2015 11:25:05 +0000 http://www.hindawi.com/journals/dm/2015/827941/ Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme , γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, , and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility. Anna Gvozdjáková, Jarmila Kucharská, Jozef Dubravicky, Viliam Mojto, and Ram B. Singh Copyright © 2015 Anna Gvozdjáková et al. All rights reserved.