Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Galectin-3 Reflects Mitral Annular Plane Systolic Excursion Being Assessed by Cardiovascular Magnetic Resonance Imaging Thu, 01 Dec 2016 14:15:38 +0000 http://www.hindawi.com/journals/dm/2016/7402784/ Background. This study investigates whether serum levels of galectin-3 may reflect impaired mitral annular plane systolic excursion (MAPSE) in patients undergoing cardiac magnetic resonance imaging (cMRI). Methods. Patients undergoing cMRI during routine clinical care were included prospectively within an all-comers design. Blood samples for biomarker measurements were collected within 24 hours following cMRI. Statistical analyses were performed in all patients and in three subgroups according to MAPSE (MAPSE I: ≥11 mm, MAPSE II: ≥8 mm–<11 mm, and MAPSE III: <8 mm). Patients with right ventricular dysfunction (<50%) were excluded. Results. 84 patients were included in the study. Median LVEF was 59% (IQR 51–64%). Galectin-3 correlated significantly with NT-proBNP (, ). Galectin-3 increased significantly according to the different stages of impaired MAPSE () and was able to discriminate both patients with impaired MAPSE <11 mm (area under the curve (AUC) = 0.645, ) and <8 mm (AUC = 0.733, ). Combining galectin-3 with NT-proBNP improved discrimination of MAPSE <8 mm (AUC 0.803, ). In multivariable logistic regression models galectin-3 was still associated with impaired MAPSE (MAPSE < 11 mm: odds ratio (OR) = 3.53, ; MAPSE < 8 mm: OR = 3.18, ). Conclusions. Galectin-3 reflects MAPSE being assessed by cardiac MRI. Seung-Hyun Kim, Michael Behnes, Michele Natale, Julia Hoffmann, Nadine Reckord, Ursula Hoffmann, Johannes Budjan, Thomas Henzler, Theano Papavassiliu, Martin Borggrefe, Thomas Bertsch, and Ibrahim Akin Copyright © 2016 Seung-Hyun Kim et al. All rights reserved. Platelets miRNA as a Prediction Marker of Thrombotic Episodes Wed, 30 Nov 2016 09:04:02 +0000 http://www.hindawi.com/journals/dm/2016/2872507/ The blood platelets are crucial for the coagulation physiology to maintain haemostatic balance and are involved in various pathologies such as atherosclerosis and thrombosis. The studies of recent years have shown that anucleated platelets are able to succeed protein synthesis. Additionally, mRNA translation in blood platelets is regulated by miRNA molecules. Recent works postulate the possibility of using miRNAs as biomarkers of atherosclerosis and ischemic episodes. This review article describes clinical studies that presented blood platelets miRNAs expression profile changes in different thrombotic states, which suggest use of these molecules as predictive biomarkers. Michal Bijak, Malgorzata Dzieciol, Joanna Rywaniak, Joanna Saluk, and Marzenna Zielinska Copyright © 2016 Michal Bijak et al. All rights reserved. Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines Mon, 28 Nov 2016 14:21:38 +0000 http://www.hindawi.com/journals/dm/2016/5179594/ Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes’ involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins. Edmund Ui-Hang Sim, Stella Li-Li Chan, Kher-Lee Ng, Choon-Weng Lee, and Kumaran Narayanan Copyright © 2016 Edmund Ui-Hang Sim et al. All rights reserved. Exome Sequencing Identifies Compound Heterozygous Mutations in SCN5A Associated with Congenital Complete Heart Block in the Thai Population Mon, 28 Nov 2016 12:19:53 +0000 http://www.hindawi.com/journals/dm/2016/3684965/ Background. Congenital heart block is characterized by blockage of electrical impulses from the atrioventricular node (AV node) to the ventricles. This blockage can be caused by ion channel impairment that is the result of genetic variation. This study aimed to investigate the possible causative variants in a Thai family with complete heart block by using whole exome sequencing. Methods. Genomic DNA was collected from a family consisting of five family members in three generations in which one of three children in generation III had complete heart block. Whole exome sequencing was performed on one complete heart block affected child and one unaffected sibling. Bioinformatics was used to identify annotated and filtered variants. Candidate variants were validated and the segregation analysis of other family members was performed. Results. This study identified compound heterozygous variants, c.101G>A and c.3832G>A, in the SCN5A gene and c.28730C>T in the TTN gene. Conclusions. Compound heterozygous variants in the SCN5A gene were found in the complete heart block affected child but these two variants were found only in the this affected sibling and were not found in other unaffected family members. Hence, these variants in the SCN5A gene were the most possible disease-causing variants in this family. Chuphong Thongnak, Pornprot Limprasert, Duangkamol Tangviriyapaiboon, Suchaya Silvilairat, Apichaya Puangpetch, Ekawat Pasomsub, Chonlaphat Sukasem, and Wasun Chantratita Copyright © 2016 Chuphong Thongnak et al. All rights reserved. Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis Wed, 23 Nov 2016 13:25:48 +0000 http://www.hindawi.com/journals/dm/2016/8486406/ Age-related macular degeneration (AMD) is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963) and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963. Martina Barchitta and Andrea Maugeri Copyright © 2016 Martina Barchitta and Andrea Maugeri. All rights reserved. The Ratio of Hmox1/Nrf2 mRNA Level in the Tumor Tissue Is a Predictor of Distant Metastasis in Colorectal Cancer Wed, 23 Nov 2016 12:40:28 +0000 http://www.hindawi.com/journals/dm/2016/8143465/ Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction. The tumor had lower Hmox1 but higher Bach1 mRNA levels than the normal tissue. The correlations of Hmox1 with components of the Nrf2 pathway were not significant in the tumor tissue of CRC subjects with distant metastasis. The ratio of Hmox1/Nrf2 mRNA level (by percentage) in the tumor tissue was lower in the subjects with distant metastasis (97.4% (84.4–111.1%)) than in those without (101.0% (92.7–136.5%)) and was a predictor for distant metastasis in CRC (odds ratio: 0.83; 95% confidence interval: 0.68–0.97) along with serum carcinoembryonic antigen (1.0027, 1.006–1.064). The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC. Liang-Che Chang, Chung-Wei Fan, Wen-Ko Tseng, Hui-Ping Chein, Tsan-Yu Hsieh, Jim-Ray Chen, Cheng-Cheng Hwang, and Chung-Ching Hua Copyright © 2016 Liang-Che Chang et al. All rights reserved. Thrombosis Related ABO, F5, MTHFR, and FGG Gene Polymorphisms in Morbidly Obese Patients Wed, 23 Nov 2016 09:00:45 +0000 http://www.hindawi.com/journals/dm/2016/7853424/ Objective. Obesity is a well-known risk factor for thrombotic complications. The aim of the present study was to determine the frequency of thrombosis related ABO, F5, MTHFR, and FGG gene polymorphisms in morbidly obese patients and compare them with the group of nonobese individuals. Methods. Gene polymorphisms were analyzed in 320 morbidly obese patients (BMI > 40 kg/m2) and 303 control individuals (BMI < 30 kg/m2) of European descent. ABO C>T (rs505922), F5 C>G (rs6427196), MTHFR C>T (rs1801133), and FGG C>T (rs6536024) SNPs were genotyped by RT-PCR. Results. We observed a tendency for MTHFR rs1801133 TT genotype to be linked with morbid obesity when compared to CC genotype; however, the difference did not reach the significant value (OR 1.84, 95% CI 0.83–4.05, ). Overall, the genotypes and alleles of rs505922, rs6427196, rs1801133, and rs6536024 SNPs had similar distribution between morbidly obese and nonobese control individuals. Distribution of height and weight means among individuals carrying different rs505922, rs6427196, rs1801133, and rs6536024 genotypes did not differ significantly. Conclusions. Gene polymorphisms ABO C>T (rs505922), F5 C>G (rs6427196), MTHFR C>T (rs1801133), and FGG C>T (rs6536024) were not associated with height, weight, or morbid obesity among European subjects. Kristina Kupcinskiene, Martyna Murnikovaite, Greta Varkalaite, Simonas Juzenas, Darius Trepenaitis, Ruta Petereit, Almantas Maleckas, Juozas Kupcinskas, and Andrius Macas Copyright © 2016 Kristina Kupcinskiene et al. All rights reserved. Plasma Cathepsin S and Cathepsin S/Cystatin C Ratios Are Potential Biomarkers for COPD Tue, 22 Nov 2016 11:09:28 +0000 http://www.hindawi.com/journals/dm/2016/4093870/ Purpose. This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD. Patients and Methods. We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR). In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA. Data were analyzed using simple and logistic regression and receiver operating characteristic analyses. Results. Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (). Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; ) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA 8.0; ). Conclusion. Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD. Takahiro Nakajima, Hidetoshi Nakamura, Caroline A. Owen, Shuichi Yoshida, Keishi Tsuduki, Shotaro Chubachi, Toru Shirahata, Shuko Mashimo, Miho Nakamura, Saeko Takahashi, Naoto Minematsu, Hiroki Tateno, Seitaro Fujishima, Koichiro Asano, Bartolome R. Celli, and Tomoko Betsuyaku Copyright © 2016 Takahiro Nakajima et al. All rights reserved. Comparative Lateralizing Ability of Multimodality MRI in Temporal Lobe Epilepsy Tue, 15 Nov 2016 10:58:27 +0000 http://www.hindawi.com/journals/dm/2016/5923243/ Purpose. The objective is to compare lateralizing ability of three quantitative MR (qMRI) modalities to depict changes of hippocampal architecture with clinical entities in temporal lobe epilepsy. Methods. We evaluated 14 patients with clinical and EEG proven diagnosis of unilateral TLE and 15 healthy volunteers. T1-weighted 3D dataset for volumetry, single-voxel 1H MR spectroscopy (MRS), and diffusion tensor imaging (DTI) were performed for bilateral hippocampi of all subjects. Results. Individual volumetric measurements provided accurate lateralization in 85% of the patients, spectroscopy in 57%, and DTI in 57%. Higher lateralization ratios were acquired combining volumetry-spectroscopy (85%), spectroscopy-DTI (85%), and volumetry-DTI (100%). Significantly decreased NAA/(Cho+Cr) ratios () and increased FA () values were obtained in ipsilateral to epileptogenic hippocampus. Duration of epilepsy and FA values showed a significant negative correlation (, ). The history of febrile convulsion associated with ipsilateral increased ADC values (, ) and reduced NAA/(Cho+Cr) ratios (, ). Conclusion. Volumetry, MRS, and DTI studies provide complementary information of hippocampal pathology. For lateralization of epileptogenic focus and preoperative examination, volumetry-DTI combination may be indicative of diagnostic accuracy. Karabekir Ercan, Hediye Pinar Gunbey, Erhan Bilir, Elcin Zan, and Halil Arslan Copyright © 2016 Karabekir Ercan et al. All rights reserved. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates Mon, 14 Nov 2016 14:26:36 +0000 http://www.hindawi.com/journals/dm/2016/4912405/ Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients. Łukasz Pietrzyk Copyright © 2016 Łukasz Pietrzyk. All rights reserved. Lymphocyte Antigen 75 Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease Mon, 14 Nov 2016 12:51:01 +0000 http://www.hindawi.com/journals/dm/2016/6485343/ Recent genome-wide association studies have rapidly improved our understanding of the molecular pathways leading to inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC). Although several reports have demonstrated that gene single nucleotide polymorphisms (SNPs) are associated with susceptibility to IBD, its precise genetic factors have not been fully clarified. Here, we performed an association analysis between lymphocyte antigen 75 (LY75) genetic variations and IBD susceptibility or phenotype. SNPs were genotyped in 51 CD patients, 94 UC patients, and 269 healthy controls of Japanese ethnicity. We detected a significant relationship with CD susceptibility for the rs16822581 LY75 SNP (). One haplotype (GT, ) was also associated with CD susceptibility, while another carrying the opposite SNP (CA) was linked to an absence of surgical history for CD. Our findings confirm that LY75 is involved in CD susceptibility and may play a role in disease activity in the Japanese population. Atsuhiro Hirayama, Satoru Joshita, Kei Kitahara, Kenji Mukawa, Tomoaki Suga, Takeji Umemura, Eiji Tanaka, and Masao Ota Copyright © 2016 Atsuhiro Hirayama et al. All rights reserved. Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations Mon, 14 Nov 2016 07:02:50 +0000 http://www.hindawi.com/journals/dm/2016/6064830/ Objective. To determine active TGF-1 (aTGF-1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-1 by PBMC. The aTGF-1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001). Patients with increased TGF-1 serum levels were more likely to have diffuse subset (p = 0.02), digital ulcers (p = 0.02), lung fibrosis (p < 0.0001), positive antitopoisomerase I (p = 0.03), and higher modified Rodnan score (p = 0.046). Most of our culture supernatant samples had undetectable levels of TGF-1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc. Andréa Tavares Dantas, Sayonara Maria Calado Gonçalves, Anderson Rodrigues de Almeida, Rafaela Silva Guimarães Gonçalves, Maria Clara Pinheiro Duarte Sampaio, Kamila de Melo Vilar, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta, Claudia Diniz Lopes Marques, Angela Luzia Branco Pinto Duarte, and Maira Galdino da Rocha Pitta Copyright © 2016 Andréa Tavares Dantas et al. All rights reserved. Matrix Metalloproteinases as a Pleiotropic Biomarker in Medicine and Biology Wed, 09 Nov 2016 09:29:52 +0000 http://www.hindawi.com/journals/dm/2016/9275204/ Jacek Kurzepa, Fatma M. El-Demerdash, and Massimiliano Castellazzi Copyright © 2016 Jacek Kurzepa et al. All rights reserved. Association of the MDM2 SNP285 Polymorphism with Cancer Susceptibility: A Meta-Analysis Mon, 07 Nov 2016 08:33:47 +0000 http://www.hindawi.com/journals/dm/2016/4585484/ The mouse double minute 2 (MDM2) gene encodes a negative regulator for p53, and the polymorphism SNP285 in the promoter region of MDM2 gene has been implicated in cancer risk, but individual published studies had inconclusive results. Therefore, we performed this meta-analysis to obtain a more precise estimation between MDM2 SNP285 polymorphism and risk of cancer. A systematic literature search was performed using the PubMed, Embase, and Chinese Biomedical (CBM) databases. Ultimately, 16 published studies comprising 14,573 cases and 9,115 controls were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of associations. Overall, MDM2 SNP285 polymorphism was significantly associated with a decreased overall cancer risk with the heterozygous model (OR = 0.89, 95% CI = 0.79–0.99), and reduced ORs were observed with other genetic models (dominant: OR = 0.90, 95% CI = 0.79–1.01 and allele comparison: OR = 0.91, 95% CI = 0.80–1.03) but not reaching statistical significance. Stratification analysis indicated a decreased risk for ovarian cancer, Caucasians, and studies with relatively large sample size. Despite some limitations, this meta-analysis indicated that the MDM2 SNP285 polymorphism was associated with a decreased cancer risk, which warrants further validation in large and well-designed studies. Ping Wang, Meilin Wang, Sanqiang Li, Lingjun Ma, Shoumin Xi, and Jing He Copyright © 2016 Ping Wang et al. All rights reserved. Effects of Ramipril and Telmisartan on Plasma Concentrations of Low Molecular Weight and Protein Thiols and Carotid Intima Media Thickness in Patients with Chronic Kidney Disease Wed, 02 Nov 2016 12:19:00 +0000 http://www.hindawi.com/journals/dm/2016/1821596/ Hypertension, a common feature in chronic kidney disease (CKD), is an independent risk factor for CKD progression and cardiovascular disease. Although inhibitors of the renin-angiotensin system (RAS) exert salutary effects on blood pressure control and proteinuria in CKD patients, their activity towards traditional and novel oxidative markers is largely unknown. We studied the effects of 6-month treatment with telmisartan versus a combination of telmisartan and ramipril on plasma concentrations of low molecular mass (LMW, including homocysteine and cysteine) and protein thiols (PSH) plasma concentration and their relationships with carotid intima media thickness (IMT), in 24 hypertensive CKD patients (age years, 8 females and 16 males). Pretreatment PSH concentrations were independently associated with IMT (, ). Neither treatment affected plasma LMW thiols, in both reduced and total form. By contrast, both treatments increased PSH plasma concentrations and reduced IMT, although significant differences were only observed in the combined treatment group. Our results suggest that the beneficial effects of combined RAS inhibitor treatment on IMT in hypertensive CKD patients may be mediated by a reduction of oxidative stress markers, particularly PSH. Angelo Zinellu, Salvatore Sotgia, Arduino A. Mangoni, Elisabetta Sotgiu, Sara Ena, Dionigia Arru, Stefano Assaretti, Angela Baralla, Andrea E. Satta, and Ciriaco Carru Copyright © 2016 Angelo Zinellu et al. All rights reserved. Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor Tue, 01 Nov 2016 10:54:21 +0000 http://www.hindawi.com/journals/dm/2016/4218989/ Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT ( and , resp.). Among clinicopathologic parameters, only expression of FAPα in stroma was associated with distant metastasis (). In univariate analysis, stromal expression of PDGFRα was associated with shorter overall survival (). In Cox multivariate analysis, stromal overgrowth and PDGFRα stromal positivity were associated with shorter overall survival ( and , resp.). Furthermore, expression of PDGFRβ in stroma was associated with shorter overall survival in patients with malignant PT (). Conclusion. Stromal expression of PDGFRα and PDGFRβ increased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression. Hye Min Kim, Yu Kyung Lee, and Ja Seung Koo Copyright © 2016 Hye Min Kim et al. All rights reserved. Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up Mon, 31 Oct 2016 13:13:34 +0000 http://www.hindawi.com/journals/dm/2016/4857917/ Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST) to alanine aminotransferase (ALT). However, the association of AST/ALT ratio with brain natriuretic peptide (BNP) levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL). There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile) was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality. Miyuki Yokoyama, Tetsu Watanabe, Yoichiro Otaki, Hiroki Takahashi, Takanori Arimoto, Tetsuro Shishido, Takuya Miyamoto, Tsuneo Konta, Yoko Shibata, Makoto Daimon, Yoshiyuki Ueno, Takeo Kato, Takamasa Kayama, and Isao Kubota Copyright © 2016 Miyuki Yokoyama et al. All rights reserved. Diagnostic Utility of ANG in Coronary Heart Disease Complicating Chronic Heart Failure: A Cross-Sectional Study Mon, 31 Oct 2016 12:46:20 +0000 http://www.hindawi.com/journals/dm/2016/2740826/ Angiogenin (ANG) has been shown to be elevated in several cardiovascular diseases. To detect its levels and diagnostic capacity in coronary heart disease (CHD) patients complicating chronic heart failure (CHF), we performed this cross-sectional study and enrolled 616 CHD patients and 53 healthy controls. According to complicating CHF or not, the patients were divided into CHF group () and CHD disease controls (), in which the CHF group was subdivided as heart failure with reduced ejection fraction (HFrEF) group or heart failure with preserved ejection fraction (HFpEF) group on the basis of left ventricular ejection fraction (LVEF), or as different NYHA class group. Their plasma ANG levels were detected using enzyme-linked immunosorbent assay (ELISA). Plasma ANG was 342.8 (IQR []), 304.5 (IQR []), and 279.7 (IQR []) ng/mL in the CHF group, CHD disease controls, and healthy controls, respectively, significantly higher in the CHF group compared with the others. Furthermore, among CHF group, ANG is dramatically higher in the HFrEF patients compared with the HFpEF patients. As for the diagnostic capacity of ANG, the area under the receiver operating characteristic curve was 0.71 (95% CI 0.63–0.78). We concluded that plasma ANG is elevated in CHD complicating CHF patients and may be a moderate discriminator of CHF from CHD or the healthy. Peng Yu, Ming Liu, Xue Yang, Ying Yu, Ji Zhao, Lei Zhang, Rui Tong, Hong Jiang, Yunzeng Zou, and Junbo Ge Copyright © 2016 Peng Yu et al. All rights reserved. Elevated Omentin Serum Levels Predict Long-Term Survival in Critically Ill Patients Thu, 27 Oct 2016 13:37:04 +0000 http://www.hindawi.com/journals/dm/2016/3149243/ Introduction. Omentin, a recently described adipokine, was shown to be involved in the pathophysiology of inflammatory and infectious diseases. However, its role in critical illness and sepsis is currently unknown. Materials and Methods. Omentin serum concentrations were measured in 117 ICU-patients (84 with septic and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were compared with 50 healthy controls. Results. Omentin serum levels of critically ill patients at admission to the ICU or after 72 hours of ICU treatment were similar compared to healthy controls. Moreover, circulating omentin levels were independent of sepsis and etiology of critical illness. Notably, serum concentrations of omentin could not be linked to concentrations of inflammatory cytokines or routinely used sepsis markers. While serum levels of omentin were not predictive for short term survival during ICU treatment, low omentin concentrations were an independent predictor of patients’ overall survival. Omentin levels strongly correlated with that of other adipokines (e.g., leptin receptor or adiponectin), which have also been identified as prognostic markers in critical illness. Conclusions. Although circulating omentin levels did not differ between ICU-patients and controls, elevated omentin levels were predictive for an impaired patients’ long term survival. Mark Luedde, Fabian Benz, Jennifer Niedeggen, Mihael Vucur, Hans-Joerg Hippe, Martina E. Spehlmann, Florian Schueller, Sven Loosen, Norbert Frey, Christian Trautwein, Alexander Koch, Tom Luedde, Frank Tacke, and Christoph Roderburg Copyright © 2016 Mark Luedde et al. All rights reserved. Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades Tue, 25 Oct 2016 15:58:08 +0000 http://www.hindawi.com/journals/dm/2016/5128720/ Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated. Lada Dyachenko, Kristina Havrysh, Anita Lytovchenko, Irina Dosenko, Stepan Antoniuk, Valeriy Filonenko, and Ramziya Kiyamova Copyright © 2016 Lada Dyachenko et al. All rights reserved. Omics Landscape in Disease Biomarkers Discovery Mon, 24 Oct 2016 13:10:06 +0000 http://www.hindawi.com/journals/dm/2016/4068252/ Monica Neagu, Caterina Longo, and Simone Ribero Copyright © 2016 Monica Neagu et al. All rights reserved. Pilot Study on MAGE-C2 as a Potential Biomarker for Triple-Negative Breast Cancer Mon, 24 Oct 2016 09:16:25 +0000 http://www.hindawi.com/journals/dm/2016/2325987/ Objective. In the current study, we measured the expression status of melanoma antigen gene c2 (MAGE-C2) in triple-negative breast cancer (TNBC) and analyzed its prognostic with the clinical pathological features of patients with TNBC. Methods. The expressions statuses of MAGE-C2 were detected in TNBC tissues and paracarcinoma tissues by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Then, we investigated the relationship of MAGE-C2 expression status and clinicopathological parameters of TNBC patients by the chi-squared test. Finally, we discussed the relations of MAGE-C2 expression state and prognosis of patients with TNBC by Kaplan-Meier method and Cox proportional hazards model. Results. High MAGE-C2 expression was found in 38.18% (42/110) of TNBC tissues. In adjacent tissues it was 9.09% (10/110). High MAGE-C2 expression in TNBC patients was closely associated with lymph node status, tumor node metastasis (TNM) stage, and lymphovascular invasion (). TNBC patients with high MAGE-C2 expression had significantly shorter survival time than low expression patients. We also found that age, lymph node status, TNM stage, lymphovascular invasion, and MAGE-C2 expression status were closely associated with overall survival of TNBC patients (). Conclusion. High MAGE-C2 expression may serve as an independent prognostic factor for TNBC patients. Qian Zhao, Wen-ting Xu, and Tuluhong Shalieer Copyright © 2016 Qian Zhao et al. All rights reserved. Plasma Levels of Pentosidine, Carboxymethyl-Lysine, Soluble Receptor for Advanced Glycation End Products, and Metabolic Syndrome: The Metformin Effect Tue, 18 Oct 2016 06:37:07 +0000 http://www.hindawi.com/journals/dm/2016/6248264/ Metabolic syndrome (MetS) is considered one of the most important public health problems. Several and controversial studies showed that the role of advanced glycation end products (AGEs) and their receptor in the development of metabolic syndrome and therapeutic pathways is still unsolved. We have investigated whether plasma pentosidine, carboxymethyl-lysine (CML), and soluble receptor for advanced glycation end products (sRAGE) levels were increased in patients with MetS and the effect of metformin in plasma levels of pentosidine, CML, and sRAGE. 80 control subjects and 86 patients were included in this study. Pentosidine, CML, and sRAGE were measured in plasma by enzyme-linked immunosorbent assay (ELISA). Plasma pentosidine, CML, and sRAGE levels were significantly increased in patients compared to control subjects (, , and , resp.). Plasma levels of pentosidine were significantly decreased in patients who received metformin compared to untreated patients (). However, there was no significant difference between patients treated with metformin and untreated patients in plasma CML levels. Plasma levels of sRAGE were significantly increased in patients who received metformin and ACE inhibitors ( and , resp.). However, in a multiple stepwise regression analysis, pentosidine, sRAGE, and drugs treatments were not independently associated. Patients with metabolic syndrome showed increased levels of AGEs such as pentosidine and CML. Metformin treatment showed a decreased level of pentosidine but not of CML. Therapeutic pathways of AGEs development should be taken into account and further experimental and in vitro studies merit for advanced research. Mohamed Haddad, Ines Knani, Hsan Bouzidi, Olfa Berriche, Mohamed Hammami, and Mohsen Kerkeni Copyright © 2016 Mohamed Haddad et al. All rights reserved. Proteomic Approaches to Biomarker Discovery in Cutaneous T-Cell Lymphoma Sun, 16 Oct 2016 16:33:53 +0000 http://www.hindawi.com/journals/dm/2016/9602472/ Cutaneous T-cell lymphoma (CTCL) is the most frequently encountered type of skin lymphoma in humans. CTCL encompasses multiple variants, but the most common types are mycosis fungoides (MF) and Sezary syndrome (SS). While most cases of MF run a mild course over a period of many years, other subtypes of CTCL are very aggressive. The rapidly expanding fields of proteomics and genomics have not only helped increase knowledge concerning the carcinogenesis and tumor biology of CTCL but also led to the discovery of novel markers for targeted therapy. Although multiple biomarkers linked to CTCL have been known for a relatively long time (e.g., CD25, CD45, CD45RA, and CD45R0), compared to other cancers (lymphoma, melanoma, colon carcinoma, head and neck cancer, renal cancer, and cutaneous B-cell lymphoma), information about the antigenicity of CTCL remains relatively limited and no dependable protein marker for CTCL has been discovered. Considering the aggressive nature of some types of CTCL, it is necessary to identify circulating molecules that can help in the early diagnosis, differentiation from inflammatory skin diseases (psoriasis, nummular eczema), and aid in predicting the prognosis and evolution of this pathology. This review aims to bring together some of the information concerning protein markers linked to CTCL, in an effort to further the understanding of the convolute processes involved in this complex pathology. Alexandra Ion, Iris Maria Popa, Laura Maria Lucia Papagheorghe, Cristina Lisievici, Mihai Lupu, Vlad Voiculescu, Constantin Caruntu, and Daniel Boda Copyright © 2016 Alexandra Ion et al. All rights reserved. RANTES Gene Polymorphisms Associated with HIV-1 Infections in Kenyan Population Sun, 16 Oct 2016 15:59:07 +0000 http://www.hindawi.com/journals/dm/2016/4703854/ Previous studies have reported that two single nucleotide polymorphisms (SNPs) in the RANTES gene promoter region, -403G/A and -28C/G, are associated with a slower rate of decline in CD4+ T cell count. In addition, as a ligand of the major HIV coreceptor CCR5, it is known to block HIV-CCR5 interactions in the course of the HIV infection cycle. This study was carried out with the aim of determining the occurrence of single nucleotide polymorphisms (SNPs) -403G > A and -28C > G in the promoter region of RANTES, in a subset of the Kenyan population. Genomic DNA was extracted from peripheral blood monocular cells and used to amplify the RANTES gene region. Restriction fragment length polymorphism was used to determine the genotypes of the RANTES gene. Out of 100 HIV infected individuals, 19% had G1 genotypes (403G/G, 28C/G), 30% (403A/A, 28C/C), and 50% (403G/A, 28C/C), while in healthy blood donors 13% had G4 (403G/A, 28C/C) genotypes, 22% (403A/A, 28C/C), and 54% (403G/A, 28C/C). HIV negative blood donors (54%) had higher risk of alteration to risk of HIV transmission compared to those who were HIV infected (50%). However, the risk to transmission and distribution differences was not significant (). The study showed that RANTES polymorphisms -403 and -28 alleles do exist in the Kenyan population. Shem P. M. Mutuiri, Helen L. Kutima, Lamech M. Mwapagha, James K. Munyao, Anthony Kebira Nyamache, Irene Wanjiru, and Samoel A. Khamadi Copyright © 2016 Shem P. M. Mutuiri et al. All rights reserved. Redox Status of β2GPI in Different Stages of Diabetic Angiopathy Thu, 13 Oct 2016 10:59:59 +0000 http://www.hindawi.com/journals/dm/2016/8246839/ We explored the redox status of beta 2 glycoprotein I (β2GPI) in different stages of diabetic angiopathy. Type 2 diabetes mellitus (T2DM) had a significantly lower proportion of reduced β2GPI as compared to healthy controls (). There was a trend that the mild coronal atherosclerosis heart disease (CAD) had higher proportion of reduced β2GPI than non-CAD and severe-CAD groups, however without significances (). The mild-A-stenosis group and mild-diabetic retinopathy (DR) groups had higher proportion of reduced β2GPI than their severely affected counterparts. The mild-slow nerve conduction velocity (NCVS) group had higher proportion of reduced β2GPI than normal nerve conduction velocity (NCVN group) and severe-NCVS groups. The proportion of reduced β2GPI was in positive correlation with 24 h urine microalbumin and total urine protein, and the proportion of reduced β2GPI was in negative correlation with serum and skin advanced glycation end products (AGEs). Taken together, our data implicate that the proportion of reduced β2GPI increased in the early stage of angiopathy and decreased with the aggravation of angiopathy. Jun Ma, Jing-Yun Zhang, Yan Liu, De-Min Yu, and Pei Yu Copyright © 2016 Jun Ma et al. All rights reserved. Overexpression of Prolyl-4-Hydroxylase-α1 Stabilizes but Increases Shear Stress-Induced Atherosclerotic Plaque in Apolipoprotein E-Deficient Mice Wed, 12 Oct 2016 13:04:32 +0000 http://www.hindawi.com/journals/dm/2016/1701637/ The rupture and erosion of atherosclerotic plaque can induce coronary thrombosis. Prolyl-4-hydroxylase (P4H) plays a central role in the synthesis of all known types of collagens, which are the most abundant constituent of the extracellular matrix in atherosclerotic plaque. The pathogenesis of atherosclerosis is thought to be in part caused by shear stress. In this study, we aimed to investigate a relationship between P4Hα1 and shear stress-induced atherosclerotic plaque. Carotid arteries of ApoE−/− mice were exposed to low and oscillatory shear stress conditions by the placement of a shear stress cast for 2 weeks; we divided 60 male ApoE−/− mice into three groups for treatments with saline (mock) (), empty lentivirus (lenti-EGFP) (), and lentivirus-P4Hα1 (lenti-P4Hα1) (). Our results reveal that after 2 weeks of lenti-P4Hα1 treatment both low and oscillatory shear stress-induced plaques increased collagen and the thickness of fibrous cap and decreased macrophage accumulation but no change in lipid accumulation. We also observed that overexpression of P4Ha1 increased plaque size. Our study suggests that P4Hα1 overexpression might be a potential therapeutic target in stabilizing vulnerable plaques. Xiao-qing Cao, Xin-xin Liu, Meng-meng Li, Yu Zhang, Liang Chen, Lin Wang, Ming-xue Di, and Mei Zhang Copyright © 2016 Xiao-qing Cao et al. All rights reserved. The Hasford Score May Predict Molecular Response in Chronic Myeloid Leukemia Patients: A Single Institution Experience Wed, 12 Oct 2016 09:51:56 +0000 http://www.hindawi.com/journals/dm/2016/7531472/ The Sokal, Hasford, and EUTOS scores were established in different treatment eras of chronic myeloid leukemia (CML). None of them was reported to predict molecular response. In this single center study we tried to reevaluate the usefulness of three main scores in TKI era. The study group included 88 CML patients in first chronic phase treated initially with standard imatinib dose. All of them achieved major molecular response (MMR) in time points defined by European LeukemiaNet (ELN). 42 patients lost MMR in a median time of 47 months and we found a significant difference in MMR maintenance between intermediate-risk (IR) and low-risk (LR) patients assessed by Hasford score. All 42 patients were switched to second-generation TKI (2G-TKI) treatment. At 18 months of 2G-TKI therapy we have still found a significant difference in BCR-ABL transcript levels and MMR rate between IR and LR groups. We did not find any of the described differences discriminating patients by Sokal or EUTOS score. In this retrospective single center analysis we found Hasford score to be useful in predicting molecular response in first chronic phase of CML patients. Jarosław Dybko, Bożena Jaźwiec, Olga Haus, Donata Urbaniak-Kujda, Katarzyna Kapelko-Słowik, Tomasz Wróbel, Tomasz Lonc, Mateusz Sawicki, Ewa Mędraś, Agnieszka Kaczmar-Dybko, and Kazimierz Kuliczkowski Copyright © 2016 Jarosław Dybko et al. All rights reserved. Survivin as a Novel Biomarker in the Pathogenesis of Acne Vulgaris and Its Correlation to Insulin-Like Growth Factor-I Mon, 10 Oct 2016 14:56:16 +0000 http://www.hindawi.com/journals/dm/2016/7040312/ Survivin, a member of the inhibitor of apoptosis protein family, has an important role in cell cycle regulation. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone with wide range of biologic effects including stimulation of lipogenesis in sebaceous glands. Their overexpression in some fibrotic disorders suggests a possible implication of both IGF-I and survivin in the pathogenesis of acne and/or acne scars. The current study aimed to assess and correlate serum levels of IGF-I and survivin in patients with active acne vulgaris and postinflammatory acne scars and to evaluate their lesional expressions in comparison to healthy controls. Serum IGF-I and survivin were estimated using commercially available ELISA kits and their tissues expressions were investigated using Western blotting. Our findings suggest that IGF-I and survivin could play potential roles in the pathogenesis of active acne vulgaris and more importantly in postinflammatory acne scars with significant positive correlation coefficient between serum levels of IGF-I and survivin which support IGF-I-/PI3K-/AKT-mediated downregulation of nuclear expression of FoxO transcription factors resulting in enhanced survivin expression. Hanan A. Assaf, Wafaa M. Abdel-Maged, Bakheet E. M. Elsadek, Mohammed H. Hassan, Mohamed A. Adly, and Soher A. Ali Copyright © 2016 Hanan A. Assaf et al. All rights reserved. Toward Noninvasive Diagnosis of IgA Nephropathy: A Pilot Urinary Metabolomic and Proteomic Study Sun, 09 Oct 2016 09:19:43 +0000 http://www.hindawi.com/journals/dm/2016/3650909/ IgA nephropathy is diagnosed by renal biopsy, an invasive procedure with a risk of significant complications. Noninvasive approaches are needed for possible diagnostic purposes and especially for monitoring disease activity or responses to treatment. In this pilot project, we assessed the utility of urine samples as source of biomarkers of IgA nephropathy. We used spot urine specimens from 19 healthy controls, 11 patients with IgA nephropathy, and 8 renal-disease controls collected on day of renal biopsy. Urine samples were analyzed using untargeted metabolomic and targeted proteomic analyses by several experimental techniques: liquid chromatography coupled with mass spectrometry, immunomagnetic isolation of target proteins coupled with quantitation by mass spectrometry, and protein arrays. No single individual biomarker completely differentiated the three groups. Therefore, we tested the utility of several markers combined in a panel. Discriminant analysis revealed that combination of seven markers, three metabolites (dodecanal, 8-hydroxyguanosine, and leukotriene C4), three proteins (α1-antitrypsin, IgA-uromodulin complex, and galactose-deficient IgA1), and heparan sulfate, differentiated patients with IgA nephropathy from patients with other renal diseases and healthy controls. Future studies are needed to validate these preliminary findings and to determine the power of these urinary markers for assessment of responses to therapy. Michaela Neprasova, Dita Maixnerova, Jan Novak, Colin Reily, Bruce A. Julian, Jan Boron, Petr Novotny, Miloslav Suchanek, Vladimir Tesar, and Petr Kacer Copyright © 2016 Michaela Neprasova et al. All rights reserved.