Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. First-Trimester Uterine Artery Doppler Analysis in the Prediction of Later Pregnancy Complications Mon, 20 Apr 2015 13:32:57 +0000 http://www.hindawi.com/journals/dm/2015/679730/ Uterine artery Doppler waveform analysis has been extensively studied in the second trimester of pregnancy as a predictive marker for the later development of preeclampsia and fetal growth restriction. The use of Doppler interrogation of this vessel in the first trimester has gained momentum in recent years. Various measurement techniques and impedance indices have been used to evaluate the relationship between uterine artery Doppler velocimetry and adverse pregnancy outcomes. Overall, first-trimester Doppler interrogation of the uterine artery performs better in the prediction of early-onset than late-onset preeclampsia. As an isolated marker of future disease, its sensitivity in predicting preeclampsia and fetal growth restriction in low risk pregnant women is moderate, at 40–70%. Multiparametric predictive models, combining first-trimester uterine artery pulsatility index with maternal characteristics and biochemical markers, can achieve a detection rate for early-onset preeclampsia of over 90%. The ideal combination of these tests and validation of them in various patient populations will be the focus of future research. Su Lynn Khong, Stefan C. Kane, Shaun P. Brennecke, and Fabrício da Silva Costa Copyright © 2015 Su Lynn Khong et al. All rights reserved. Macrophage Migration Inhibitory Factor Promoter Polymorphisms (−794 CATT5–8 and −173 G>C): Relationship with mRNA Expression and Soluble MIF Levels in Young Obese Subjects Mon, 20 Apr 2015 11:50:51 +0000 http://www.hindawi.com/journals/dm/2015/461208/ We analyzed the relationship of −794 and −173 G>C MIF polymorphisms with mRNA and soluble MIF in young obese subjects. A total of 250 young subjects, 150 normal-weight and 100 obese subjects, were recruited in the study. Genotyping of −794 and −173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP, respectively. MIF mRNA expression was determined by real-time PCR and serum MIF levels were measured using an ELISA kit. For both MIF promoter polymorphisms, no significant differences in the genotype and allele frequencies between groups were observed. MIF mRNA expression was slightly higher in obese subjects than in normal-weight subjects (1.38-fold), while soluble MIF levels did not show differences between groups. In addition, we found an increase in MIF mRNA expression in carriers of the 6,6 and C/C genotypes and the 6G haplotype of the −794 and −173 G>C MIF polymorphisms, although it was not significant. In conclusion, this study found no relationship between obesity and MIF gene promoter polymorphisms with MIF mRNA expression in young obese subjects. Inés Matia-García, Lorenzo Salgado-Goytia, José F. Muñoz-Valle, Samuel García-Arellano, Jorge Hernández-Bello, Aralia B. Salgado-Bernabé, and Isela Parra-Rojas Copyright © 2015 Inés Matia-García et al. All rights reserved. Cardiac Biomarkers Sun, 19 Apr 2015 08:27:38 +0000 http://www.hindawi.com/journals/dm/2015/370569/ Johannes Mair, Allan Jaffe, Fred Apple, and Bertil Lindahl Copyright © 2015 Johannes Mair et al. All rights reserved. Biomarkers of Hemodynamic Stress and Aortic Stiffness after STEMI: A Cross-Sectional Analysis Thu, 16 Apr 2015 14:07:50 +0000 http://www.hindawi.com/journals/dm/2015/717032/ Aim. Increased aortic stiffness might adversely affect cardiac structure, function, and perfusion. Release of biomarkers of hemodynamic stress is thought to be enhanced by these alterations. We aimed to evaluate the association between biomarkers of hemodynamic stress and aortic stiffness assessed at a chronic stage after ST-segment elevation myocardial infarction (STEMI). Methods. Fifty-four patients four months after STEMI were enrolled in this cross-sectional, single-center study. N-terminal pro–B-type natriuretic peptide (NT-proBNP), mid-regional pro–A-type natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin (MR-proADM) levels were measured by established assays. Aortic stiffness was assessed by the measurement of pulse wave velocity using phase-contrast cardiovascular magnetic resonance. Results. NT-proBNP, MR-proANP, and MR-proADM concentrations were all correlated with aortic stiffness in univariate analysis (, , and ; all , resp.). In multiple linear regression analysis, NT-proBNP (, ) and MR-proADM (, ) levels were associated with increased aortic stiffness independently of age, blood pressure, and renal function. NT-proBNP was the strongest predictor for high aortic stiffness (area under the curve: 0.82, 95% CI 0.67–0.96). Conclusion. At a chronic stage after STEMI, concentrations of biomarkers for hemodynamic stress, especially NT-proBNP, are positively correlated with aortic stiffness. These biomarkers might also be useful as predictors of high aortic stiffness after STEMI. Sebastian Johannes Reinstadler, Hans-Josef Feistritzer, Gert Klug, Agnes Mayr, Luc Huybrechts, Angelika Hammerer-Lercher, Johannes Mair, Wolfgang-Michael Franz, and Bernhard Metzler Copyright © 2015 Sebastian Johannes Reinstadler et al. All rights reserved. Diagnostic Implications of an Elevated Troponin in the Emergency Department Thu, 16 Apr 2015 14:02:36 +0000 http://www.hindawi.com/journals/dm/2015/157812/ Objective. To determine the proportion of initial troponin (cTn) elevations associated with Type I MI versus other cardiovascular and noncardiovascular diagnoses in an emergency department (ED) and whether or not a relationship exists between the cTn level and the likelihood of Type I MI. Background. In the ED, cTn is used as a screening test for myocardial injury. However, the differential diagnosis for an initial positive cTn result is not clear. Methods. Hospital medical records were retrospectively reviewed for visits associated with an initial positive troponin I-ultra (cTnI), ≥0.05 μg/L. Elevated cTnI levels were stratified into low (0.05–0.09), medium (0.1–0.99), or high (≥1.0). Discharge diagnoses were classified into 3 diagnostic groups (Type I MI, other cardiovascular, or noncardiovascular). Results. Of 23,731 ED visits, 4,928 (21%) had cTnI testing. Of those tested, 16.3% had initial cTnI ≥0.05. Among those with elevated cTn, 11% were classified as Type I MI, 34% had other cardiovascular diagnoses, and 55% had a noncardiovascular diagnosis. Type I MI was more common with high cTnI levels (41% incidence) than among subjects with medium (9%) or low (6%). Conclusion. A positive cTn is most likely a noncardiovascular diagnosis, but Type I MI is far more common with cTnI levels ≥1.0. Maame Yaa Yiadom, Petr Jarolim, Cathy Jenkins, Stacy E. F. Melanson, Michael Conrad, and Joshua M. Kosowsky Copyright © 2015 Maame Yaa Yiadom et al. All rights reserved. Short Communication: Relationship between Urinary Neutrophil Gelatinase-Associated Lipocalin and Noninfectious Pyuria in Dogs Thu, 16 Apr 2015 13:15:22 +0000 http://www.hindawi.com/journals/dm/2015/387825/ Neutrophil gelatinase-associated lipocalin (NGAL) is a neutrophil-derived protein whose concentration increases in plasma and urine with ongoing renal damage. Urinary leucocytes can be a potential source of urinary NGAL. The aim of this study is to investigate the effects of urinary neutrophil count and other urinary parameters on urinary NGAL values in urine with negative culture. Urinalysis, urine culture, and determination of urinary NGAL were performed on 33 clinically healthy nonproteinuric dogs with negative urinoculture. The median uNGAL concentration in dogs in this study population was 9.74 ng/mL (IQR 1.93–25.43 ng/mL). In samples with WBCs > 5 hpf (mean 15.9, 6–50 leucocytes/hpf), median uNGAL value was significantly higher than that in samples with WBCs < 5 hpf (mean 0.9, 0–3 leucocytes/hpf), (4.96 pg/mL (0.29–11.34) and 23.65 pg/mL (20.04–29.80), resp.; ). The severity of urinary pyuria and the UPC value were correlated with uNGAL concentration. The results of our study show that urinary NGAL concentration is correlated with WBCs number in urinary sediment of dogs with negative urinoculture. The present study suggests that noninfectious pyuria is significantly correlated with urinary NGAL values and might influence uNGAL values. D. Proverbio, E. Spada, L. Baggiani, G. Bagnagatti De Giorgi, E. Ferro, P. A. Martino, and R. Perego Copyright © 2015 D. Proverbio et al. All rights reserved. Copeptin Testing in Acute Myocardial Infarction: Ready for Routine Use? Thu, 16 Apr 2015 11:13:31 +0000 http://www.hindawi.com/journals/dm/2015/614145/ Suspected acute myocardial infarction is one of the leading causes of admission to emergency departments. In the last decade, biomarkers revolutionized the management of patients with suspected acute coronary syndromes. Besides their pivotal assistance in timely diagnosis, biomarkers provide additional information for risk stratification. Cardiac troponins I and T are the most sensitive and specific markers of acute myocardial injury. Nonetheless, in order to overcome the remaining limitations of these markers, novel candidate biomarkers sensitive to early stage of disease are being extensively investigated. Among them, copeptin, a stable peptide derived from the precursor of vasopressin, emerged as a promising biomarker for the evaluation of suspected acute myocardial infarction. In this review, we summarize the currently available evidence for the usefulness of copeptin in the diagnosis and risk stratification of patients with suspected acute myocardial infarction in comparison with routine biomarkers. Sebastian Johannes Reinstadler, Gert Klug, Hans-Josef Feistritzer, Bernhard Metzler, and Johannes Mair Copyright © 2015 Sebastian Johannes Reinstadler et al. All rights reserved. Evaluation of High Sensitive Troponin in Erectile Dysfunction Thu, 16 Apr 2015 08:31:16 +0000 http://www.hindawi.com/journals/dm/2015/548951/ Background. Evidence is accumulating in favour of a link between erectile dysfunction (ED) and coronary artery diseases. We investigated the presence of cardiac injury in patients who have had arteriogenic and nonarteriogenic ED using the hs-Tn levels. Methods. The diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire (IIF-5) and patients were classified as arteriogenic (A-ED, ), nonarteriogenic (NA-ED, ), and borderline (BL-ED, ) patients in relation to the results of echo-color-Doppler examination of cavernous arteries. The level of hs-TnT and hs-TnI was measured in 120 men with a history of ED of less than one year with no clinical evidence of cardiac ischemic disease. Results. The levels of both hs-TnT and hs-TnI were within the reference range and there was no significant () difference between patients of the three groups. The hs-CRP values were higher in A-ED men compared with NA-ED () but not compared with BL-ED () and negatively correlated with IIF-5 (; ). Conclusions. In ED patients of the three groups the measurement of hs-Tn allows us to exclude the presence of cardiac involvement at least when the history of ED is less than one year and the men are without atherosclerotic risk factors. Alessandra Barassi, Raffaele Pezzilli, Antonio Maria Morselli-Labate, Elena Dozio, Luca Massaccesi, Francesca Ghilardi, Clara Anna Linda Damele, Giovanni Maria Colpi, Gian Vico Melzi d’Eril, and Massimiliano Marco Corsi Romanelli Copyright © 2015 Alessandra Barassi et al. All rights reserved. Prognostic Value of Galectin-3 in Patients with Heart Failure Thu, 16 Apr 2015 07:39:32 +0000 http://www.hindawi.com/journals/dm/2015/690205/ Galectins are a family of soluble β-galactoside-binding lectins that have important role in inflammation, immunity, and cancer. Galectin-3 as a part of this lectin family plays a very important role in development of heart failure. According to recent papers, galectin-3 plasma level correlates with heart failure outcome, primarily with rehospitalisation and death from heart failure. This paper summarizes the most recent advances in galectin-3 research, with the accent on the role of galectin-3 in pathophysiology of myocardial remodelling and heart failure development—with preserved and reduced ejection fraction, and some implication on development of new disease modifying drugs. Ivica Bošnjak, Kristina Selthofer-Relatić, and Aleksandar Včev Copyright © 2015 Ivica Bošnjak et al. All rights reserved. NT-proBNP as Early Marker of Subclinical Late Cardiotoxicity after Doxorubicin Therapy and Mediastinal Irradiation in Childhood Cancer Survivors Thu, 16 Apr 2015 07:02:53 +0000 http://www.hindawi.com/journals/dm/2015/513219/ Background. Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity. Aims of the Study. To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation. Methods. A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin’s lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined. Results. Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy. Conclusions. TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity. Amal Zidan, Laila M. Sherief, Amera El-sheikh, Safaa H. Saleh, Doaa A. Shahbah, Naglaa M. Kamal, Hanan S. Sherbiny, and Heba Ahmad Copyright © 2015 Amal Zidan et al. All rights reserved. Association between Plasma Fibrinogen Levels and Mortality in Acute-on-Chronic Hepatitis B Liver Failure Thu, 16 Apr 2015 06:14:49 +0000 http://www.hindawi.com/journals/dm/2015/468596/ Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672–0.820, ), and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094–0.983; ). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients. Zhexin Shao, Ying Zhao, Limin Feng, Guofang Feng, Juanwen Zhang, and Jie Zhang Copyright © 2015 Zhexin Shao et al. All rights reserved. Vimentin 3, the New Hope, Differentiating RCC versus Oncocytoma Tue, 07 Apr 2015 14:10:34 +0000 http://www.hindawi.com/journals/dm/2015/368534/ Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients’ survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients’ tumor samples may result. Melanie von Brandenstein, Katharina Puetz, Monika Schlosser, Heike Löser, Joachim P. Kallinowski, Daniel Gödde, Reinhard Buettner, Stefan Störkel, and Jochen W. U. Fries Copyright © 2015 Melanie von Brandenstein et al. All rights reserved. The Relationship between Clinical Feature, Complex Immunophenotype, Chromosome Karyotype, and Outcome of Patients with Acute Myeloid Leukemia in China Tue, 07 Apr 2015 13:05:38 +0000 http://www.hindawi.com/journals/dm/2015/382186/ Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly+AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly−AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall survival (OS) and relapse-free survival (RFS) in MPAL patients were significantly shorter than those in Ly+AML and Ly−AML. With regard to the patients with normal karyotype only, the OS and RFS of MPAL were significantly lower than those of the Ly+AML and Ly−AML; but there were no significant differences in OS and RFS among the patients with complex karyotype. The OS rates of 3 groups with complex karyotype were lower than those of patients with normal karyotype. In Cox multivariate analysis, complex karyotype was an independent pejorative factor for both OS and RFS. Therefore, MPAL is confirmed to be a poor-risk disease while Ly+AML does not impact prognosis. Complex karyotype is an unfavorable prognosis factor in AML patients with different immunophenotype. Mixed immunophenotype and complex karyotype increase the adverse risk when they coexist. Bingjie Ding, Lanlan Zhou, Xuejie Jiang, Xiaodong Li, Qingxiu Zhong, Zhixiang Wang, Zhengshan Yi, Zhongxin Zheng, Changxin Yin, Rui Cao, Libin Liao, and Fanyi Meng Copyright © 2015 Bingjie Ding et al. All rights reserved. Association of High Expression of Groβ with Clinical and Pathological Characteristics of Unfavorable Prognosis in Gastrointestinal Stromal Tumors Tue, 07 Apr 2015 09:13:13 +0000 http://www.hindawi.com/journals/dm/2015/171035/ GROβ (CXCL2) is a chemokine produced by endotoxin-treated macrophages that mediates inflammation and tumor development. However, little is known about GROβ expression in gastrointestinal stromal tumors (GIST) or the relationship between GROβ expression and clinical attributes of GIST. GROβ expression was examined via immunohistochemical staining of 173 GIST samples using tissue microarray. The relationship between GROβ expression and relevant patient and tumor characteristics was assessed, using chi-square tests. Univariate and multivariate analysis was carried out using the Cox regression method. High GROβ cytoplasm staining was detected in 56 (32.4%) specimens; high GROβ nuclear staining was detected in 64 (37.0%) specimens. High GROβ cytoplasm staining was significantly associated with patients’ age () and tumor location (), while high GROβ nucleus staining was significantly associated with mitotic index (), tumor location (), and AFIP-Miettinen risk classification (). Kaplan-Meier survival curves showed GIST patients with low GROβ cytoplasm expression () and mitotic index < 6 per 50 HPFs () to have a more favorable prognosis. These findings indicate that GROβ expression correlates with malignant GIST phenotypes and could be an unfavorable prognostic marker in patients with GIST. Hui Zhao, Huijun Zhu, Qin Jin, Shu Zhang, Wei Wang, Defeng Wang, and Jianfei Huang Copyright © 2015 Hui Zhao et al. All rights reserved. Characterization of Clinical and Genetic Risk Factors Associated with Dyslipidemia after Kidney Transplantation Mon, 06 Apr 2015 11:49:50 +0000 http://www.hindawi.com/journals/dm/2015/179434/ We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients and treatment with high mycophenolate mofetil and prednisolone doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype . A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8–12.2). These findings may aid in predicting a patient’s risk of developing dyslipidemia. Kazuyuki Numakura, Hideaki Kagaya, Ryohei Yamamoto, Naoki Komine, Mitsuru Saito, Tsuruta Hiroshi, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Takenori Niioka, Masatomo Miura, and Shigeru Satoh Copyright © 2015 Kazuyuki Numakura et al. All rights reserved. CYP7A1 Gene Polymorphism Located in the 5′ Upstream Region Modifies the Risk of Coronary Artery Disease Mon, 06 Apr 2015 07:35:07 +0000 http://www.hindawi.com/journals/dm/2015/185969/ Background. 7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic conversion pathway leading from cholesterol to bile acids synthesis, is encoded by CYP7A1 gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid levels and may be related to impaired lipid profile leading to coronary artery disease (CAD). The aim of the present study was to analyze the possible association between the rs7833904 CYP7A1 polymorphism and premature CAD. Material and Methods. Serum lipid levels and rs7833904 SNP were determined in 419 subjects: 200 patients with premature CAD and 219 age and sex matched controls. Results. The A allele carrier state was associated with CAD (OR = 1.76, 95% CI; 1.14–2.71, ). The effect was even stronger in the male subgroups (OR = 2.16, 95% CI; 1.28–3.65, ). There was no effect in the females. Risk factors of CAD and clinical phenotype of atherosclerosis were not associated with genotype variants of the rs7833904 SNP. Lipid profiles also did not differ significantly between individual genotypes. Conclusion. The CYP7A1 rs7833904 polymorphism may modify the risk of CAD. This effect is especially strong in male subjects. The studied polymorphism does not significantly influence serum lipid levels, in the present study. Tomasz Iwanicki, Anna Balcerzyk, Pawel Niemiec, Tomasz Nowak, Anna Ochalska-Tyka, Jolanta Krauze, Sylwia Kosiorz-Gorczynska, Wladyslaw Grzeszczak, and Iwona Zak Copyright © 2015 Tomasz Iwanicki et al. All rights reserved. Chaperonin-Containing t-Complex Protein-1 Subunit β as a Possible Biomarker for the Phase of Glomerular Hyperfiltration of Diabetic Nephropathy Sun, 05 Apr 2015 12:49:40 +0000 http://www.hindawi.com/journals/dm/2015/548101/ In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit β (TCP-1β) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1β and type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (), and kidney tissues were harvested for evaluation of TCP-1β expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed that and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1β was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed. Chung-Ze Wu, Li-Chien Chang, Yuh-Feng Lin, Yi-Jen Hung, Dee Pei, and Jin-Shuen Chen Copyright © 2015 Chung-Ze Wu et al. All rights reserved. Cardiovascular Biomarkers in Chronic Kidney Disease: State of Current Research and Clinical Applicability Sun, 05 Apr 2015 10:29:21 +0000 http://www.hindawi.com/journals/dm/2015/586569/ The high incidence of cardiovascular events in chronic kidney disease (CKD) warrants an accurate evaluation of risk aimed at reducing the burden of disease and its consequences. The use of biomarkers to identify patients at high risk has been in use in the general population for several decades and has received mixed reactions in the medical community. Some practitioners have become staunch supporters and users while others doubt the utility of biomarkers and rarely measure them. In CKD patients numerous markers similar to those used in the general population and others more specific to the uremic population have emerged; however their utility for routine clinical application remains to be fully elucidated. The reproducibility and standardization of the serum assays are serious limitations to the broad implementation of these tests. The lack of focused research and validation in randomized trials rather than ad hoc measurement of multiple serum markers in observational studies is also cause for concern related to the clinical applicability of these markers. We review the current literature on biomarkers that may have a relevant role in field of nephrology. Luis D’Marco, Antonio Bellasi, and Paolo Raggi Copyright © 2015 Luis D’Marco et al. All rights reserved. Overexpression of FRAT1 Is Associated with Malignant Phenotype and Poor Prognosis in Human Gliomas Thu, 02 Apr 2015 18:16:10 +0000 http://www.hindawi.com/journals/dm/2015/289750/ Glioma is the most common malignancy of the central nervous system. Approximately 40 percent of intracranial tumors are diagnosed as gliomas. Difficulties in treatment are associated closely with the malignant phenotype, which is characterized by excessive proliferation, relentless invasion, and angiogenesis. Although the comprehensive treatment level of brain glioma is continuously progressing, the outcome of this malignancy has not been improved drastically. Therefore, the identification of new biomarkers for diagnosis and therapy of this malignancy is of significant scientific and clinical value. FRAT1 is a positive regulator of the Wnt/β-catenin signaling pathway and is overexpressed in many human tumors. In the present study, we investigated the expression status of FRAT1 in 68 patients with human gliomas and its correlation with the pathologic grade, proliferation, invasion, angiogenesis, and prognostic significance. These findings suggest that FRAT1 may be an important factor in the tumorigenesis and progression of glioma and could be explored as a potential biomarker for pathological diagnosis, an indicator for prognosis, and a target for biological therapy of malignancy. Geng Guo, Cheng-liang Zhong, Yang Liu, Xing-gang Mao, Zheng Zhang, Ji Jin, Jing Liu, Liu Yang, Jin-ming Mao, Yu-hong Guo, and Yuan-li Zhao Copyright © 2015 Geng Guo et al. All rights reserved. Serum and Urine Biomarkers for Human Renal Cell Carcinoma Thu, 02 Apr 2015 09:54:48 +0000 http://www.hindawi.com/journals/dm/2015/251403/ Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called “targeted therapies.” The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients. A. L. Pastore, G. Palleschi, L. Silvestri, D. Moschese, S. Ricci, V. Petrozza, A. Carbone, and A. Di Carlo Copyright © 2015 A. L. Pastore et al. All rights reserved. Long-Term Outcomes of Hepatic Resection versus Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Propensity Score-Matching Study Wed, 01 Apr 2015 14:02:07 +0000 http://www.hindawi.com/journals/dm/2015/425926/ Hepatic resection (HR) and liver transplantation (LT) are surgical treatment options for hepatocellular carcinoma (HCC). However, it is clinically impossible to perform a randomized, controlled study to determine the usefulness of these treatments. The present study compared survival rates and recurrence rates of HR versus living donor LT (LDLT) for HCC by using the propensity score method. Between January 1999 and August 2012, 936 patients (732 HR, 204 LDLT) underwent surgical therapy for HCC in our center. Using the propensity score matching, 80 well-balanced patients were defined. The 1- and 5-year overall survival rates were 90% and 53% in the HR group and 82% and 63% in the LT group, respectively. They were not significantly different between the two groups. The odds ratio estimated using the propensity score matching analysis was 0.842 (). The 1- and 5-year recurrence rates were significantly lower in the LT group (9% and 21%) than in the HR group (43% and 74%) (), and the odds ratio was 0.214 (). In conclusion, HR should be considered a valid alternative to LDLT taking into consideration the risk for the living donor based on the results of this propensity score-matching study. Toshimi Kaido, Satoshi Morita, Sachiko Tanaka, Kohei Ogawa, Akira Mori, Etsuro Hatano, and Shinji Uemoto Copyright © 2015 Toshimi Kaido et al. All rights reserved. Prognostic Value of Pentraxin-3 Level in Patients with STEMI and Its Relationship with Heart Failure and Markers of Oxidative Stress Wed, 01 Apr 2015 09:32:16 +0000 http://www.hindawi.com/journals/dm/2015/159051/ Objective. Pentraxin-3 (PTX3) appears to have a cardioprotective effect through a positive influence against postreperfusion damage. This study assesses the prognostic value of PTX3 level and its relationship with clinical parameters and markers of oxidative stress and nitric oxide metabolism in patients with ST-elevation myocardial infarction (STEMI). Methods. Plasma/serum levels of several biomarkers of inflammation and oxidative stress and nitrite/nitrate were assessed upon admission and 24 h after STEMI onset in patients treated by primary percutaneous coronary intervention. Results. ROC analysis showed that plasma PTX3 at 24 h was a strong predictor of 30-day and 1-year mortality and independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. The inflammatory response expressed by PTX3 had a significant relationship with age, heart failure, infarct size, impaired flow in the infarct-related artery, and renal function and positively correlated with neopterin, TNF-α, 8-hydroxy-2′-deoxyguanosine, and nitrite/nitrate. Conclusions. Plasma PTX3 at 24 h after STEMI onset is a strong predictor of 30-day and 1-year mortality. PTX3 as a single biomarker is comparable with currently used scoring systems (TIMI or GRACE) or B-type natriuretic peptide. PTX3 is also an independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. Marie Tomandlova, Jiri Jarkovsky, Josef Tomandl, Lenka Kubkova, Petr Kala, Simona Littnerova, Jana Gottwaldova, Petr Kubena, Eva Ganovska, Martin Poloczek, Jindrich Spinar, Christian Mueller, Alexandre Mebazaa, Monika Pavkova Goldbergova, and Jiri Parenica Copyright © 2015 Marie Tomandlova et al. All rights reserved. MicroRNA-155 Hallmarks Promising Accuracy for the Diagnosis of Various Carcinomas: Results from a Meta-Analysis Mon, 30 Mar 2015 12:18:22 +0000 http://www.hindawi.com/journals/dm/2015/327287/ Background. Recent studies have shown that microRNAs (miRNAs) have diagnostic values in various cancers. This meta-analysis seeks to summarize the global diagnostic role of miR-155 in patients with a variety of carcinomas. Methods. Eligible studies were retrieved by searching the online databases, and the bivariate meta-analysis model was employed to generate the summary receiver operator characteristic (SROC) curve. Results. A total of 17 studies dealing with various carcinomas were finally included. The results showed that single miR-155 testing allowed for the discrimination between cancer patients and healthy donors with a sensitivity of 0.82 (95% CI: 0.73–0.88) and specificity of 0.77 (95% CI: 0.70–0.83), corresponding to an area under curve (AUC) of 0.85, while a panel comprising expressions of miR-155 yielded a sensitivity of 0.76 (95% CI: 0.68–0.82) and specificity of 0.82 (95% CI: 0.77–0.86) in diagnosing cancers. The subgroup analysis displayed that serum miR-155 test harvested higher accuracy than plasma-based assay (the AUC, sensitivity, and specificity were, resp., 0.87 versus 0.73, 0.78 versus 0.74, and 0.77 versus 0.70). Conclusions. Our data suggest that single miR-155 profiling has a potential to be used as a screening test for various carcinomas, and parallel testing of miR-155 confers an improved specificity compared to single miR-155 analysis. Chuancheng Wu, Qiuyan Liu, and Baoying Liu Copyright © 2015 Chuancheng Wu et al. All rights reserved. Assessment of Glomerular Filtration Rate Based on Alterations of Serum Brain-Derived Neurotrophic Factor in Type 2 Diabetic Subjects Treated with Amlodipine/Benazepril or Valsartan/Hydrochlorothiazide Mon, 30 Mar 2015 11:58:49 +0000 http://www.hindawi.com/journals/dm/2015/780743/ Background. Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. Methods. In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. Results. Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (, ) but not in the 77 subjects treated with benazepril/amlodipine (, ). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR ( mL/min/1.73 m2; ). Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between −0.887 and −0.076, ). Conclusions. Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril. I-Te Lee, Wayne Huey-Herng Sheu, Yi-Jen Hung, Jung-Fu Chen, Chih-Yuan Wang, and Wen-Jane Lee Copyright © 2015 I-Te Lee et al. All rights reserved. The Analysis of Sialylation, N-Glycan Branching, and Expression of O-Glycans in Seminal Plasma of Infertile Men Sun, 29 Mar 2015 11:50:51 +0000 http://www.hindawi.com/journals/dm/2015/941871/ Carbohydrates are known to mediate some events involved in successful fertilization. Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. Extension of the lectin panel is useful for the further research. Ewa M. Kratz, Anna Kałuża, Mariusz Zimmer, and Mirosława Ferens-Sieczkowska Copyright © 2015 Ewa M. Kratz et al. 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.