Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Serum Levels of Progranulin Are Closely Associated with Microvascular Complication in Type 2 Diabetes Thu, 28 May 2015 10:50:06 +0000 http://www.hindawi.com/journals/dm/2015/357279/ Objective. Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the correlation between PGRN and type 2 diabetics with microvascular complications. Methods. PGRN serum levels and glucose metabolism related substance were measured in 84 type 2 diabetic patients with or without microangiopathies and 12 health persons. Further analyses of serum PGRN in different stages of diabetic microangiopathies were conducted. Results. Serum levels of PGRN were markedly higher in type 2 diabetic patients with microangiopathies. PGRN serum levels increased with the progress of diabetic microangiopathies with significantly highest values detectable in clinical diabetic nephropathy (CDN) and proliferative diabetic retinopathy (PDR) groups. Serum PGRN concentrations in all individuals positively and markedly correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), urinary albumin excretion rate (UAER), blood urea nitrogen (BUN), creatinine (CRE), white blood cell (WBC), disease duration, IL-6, and TNF-α, while correlating negatively and significantly with eGFR. Multiple linear regression analysis showed that only UAER and CRE were independently associated with serum PGRN. Conclusion. PGRN might be considered as a marker for diabetic microangiopathy and its severity. Lin Xu, Bo Zhou, Huixia Li, Jiali Liu, Junhui Du, Weijin Zang, Shufang Wu, and Hongzhi Sun Copyright © 2015 Lin Xu et al. All rights reserved. Uric Acid as a Marker of Kidney Disease: Review of the Current Literature Wed, 27 May 2015 13:41:59 +0000 http://www.hindawi.com/journals/dm/2015/382918/ Uric acid has been implicated in the pathophysiology of renal disease; however renal clearance makes a causal relationship difficult to prove. We examine the current literature to support a potential role of uric acid in the development of kidney disease and to determine the potential to use uric acid as a marker for future renal decline. After review, we conclude that uric acid is definitively linked to the development of chronic kidney disease and can be a poor prognostic factor for the development of acute renal failure, as well. However, further human research is needed before predictive models utilizing uric acid can be developed and used in the clinical setting. Christin Giordano, Olga Karasik, Kelli King-Morris, and Abdo Asmar Copyright © 2015 Christin Giordano et al. All rights reserved. Hyperoxia-Induced Protein Alterations in Renal Rat Tissue: A Quantitative Proteomic Approach to Identify Hyperoxia-Induced Effects in Cellular Signaling Pathways Wed, 27 May 2015 12:31:22 +0000 http://www.hindawi.com/journals/dm/2015/964263/ Introduction. In renal tissue as well as in other organs, supranormal oxygen pressure may lead to deleterious consequences on a cellular level. Additionally, hyperoxia-induced effect in cells and related free radicals may potentially contribute to renal failure. The aim of this study was to analyze time-dependent alterations of rat kidney protein expression after short-term normobaric hyperoxia using proteomics and bioinformatic approaches. Material and Methods. Wistar rats were randomized into six different groups: three groups with normobaric hyperoxia (exposure to 100% oxygen for 3 h) and three groups with normobaric normoxia (NN; room air). After hyperoxia exposure, kidneys were removed immediately, after 3 days and after 7 days. Kidney lysates were analyzed by two-dimensional gel electrophoresis followed by peptide mass fingerprinting using tandem mass spectrometry. Statistical analysis was performed with DeCyder 2D software (). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis and PathwayStudio). Results. Expression of 14 proteins was significantly altered : eight proteins (MEP1A_RAT, RSSA_RAT, F16P1_RAT, STML2_RAT, BPNT1_RAT, LGMN_RAT, ATPA_RAT, and VDAC1_RAT) were downregulated and six proteins (MTUS1_RAT, F16P1_RAT, ACTG_RAT, ACTB_RAT, 2ABA_RAT, and RAB1A_RAT) were upregulated. Bioinformatic analyses revealed an association of regulated proteins with inflammation. Conclusions. Significant alterations in renal protein expression could be demonstrated for up to 7 days even after short-term hyperoxia. The identified proteins indicate an association with inflammation signaling cascades. MEP1A and VDAC1 could be promising candidates to identify hyperoxic injury in kidney cells. Jochen Hinkelbein, Lennert Böhm, Oliver Spelten, David Sander, Stefan Soltész, and Stefan Braunecker Copyright © 2015 Jochen Hinkelbein et al. All rights reserved. Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment Tue, 26 May 2015 06:59:18 +0000 http://www.hindawi.com/journals/dm/2015/901312/ Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV) sustained by the levels of antiviral capsid antigen (VCA) and anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG has been described. Our goal was to verify the utility of EBV-specific IgG as a marker in Natalizumab treated MS. Twenty patients (17 female and 3 male) in treatment with Natalizumab were enrolled. Serum levels of anti-VCA and anti-EBNA-1 IgG were determined and expressed as arbitrary units (AU) before treatment and every three months for 21 months of therapy. Anti-VCA IgG levels were increased at the 15th month (235410 ± 196712 AU) comparing with the 3rd (98146 ± 47145 AU) and the 6th (109866 ± 52270 AU) months of therapy . No significant differences were found for serum anti-EBNA-1 IgG levels. Our data indicate that a transient, self-limited, EBV reactivation can occur in MS during Natalizumab therapy but our results do not support the use of serum EBV-specific antibody levels as biomarkers for monitoring therapeutic response to Natalizumab in the course of MS. Massimiliano Castellazzi, Serena Delbue, Francesca Elia, Matteo Gastaldi, Diego Franciotta, Roberta Rizzo, Tiziana Bellini, Roberto Bergamaschi, Enrico Granieri, and Enrico Fainardi Copyright © 2015 Massimiliano Castellazzi et al. All rights reserved. Association of PRPS1 Mutations with Disease Phenotypes Sun, 24 May 2015 06:37:24 +0000 http://www.hindawi.com/journals/dm/2015/127013/ Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum of PRPS1-related diseases. The purpose of this review is to evaluate current literature on PRPS1-related syndromes and summarize potential therapies. The overexpression of PRPS1 results in PRS-I superactivity resulting in purine overproduction. Patients with PRS-I superactivity demonstrate uric acid overproduction, hypotonia, ataxia, neurodevelopment abnormalities, and postlingual hearing impairment. On the other hand, decreased activity leads to X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome depending on the residual activity of PRS-I. Mild PRS-I deficiency (DFNX-2) results in non-syndromic progressive hearing loss whereas moderate PRS-I deficiency (CMTX5) and severe PRS-I deficiency (Arts syndrome) present with peripheral or optic neuropathy, prelingual progressive sensorineural hearing loss, and central nervous system impairment. Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in patients with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients and open new avenues of therapeutic intervention. Rahul Mittal, Kunal Patel, Jeenu Mittal, Brandon Chan, Denise Yan, M’hamed Grati, and Xue Zhong Liu Copyright © 2015 Rahul Mittal et al. All rights reserved. Monitoring of Serial Presurgical and Postsurgical Changes in the Serum Proteome in a Series of Patients with Calcific Aortic Stenosis Wed, 20 May 2015 16:40:33 +0000 http://www.hindawi.com/journals/dm/2015/694120/ Background. Comprehensive analysis of proteome differentially expressed in response to surgery or drug treatment is useful to understand biological responses to dispensed interventions. Here we investigated expression changes in sera of patients who suffered from calcific aortic stenosis (CAS), before and after surgery for aortic valve replacement. Materials and Methods. Sera obtained before and after surgery with depletion of highly abundant proteins were analyzed with iTRAQ labeling followed by nanoLC-MALDI-TOF/TOF-MS/MS. Results. Fifty-one proteins shared in five patients were identified with differential levels in postsurgical and presurgical sera. Finally, 16 proteins that show statistically significant levels in patients’ sera compared with those in control sera () were identified. Most of the identified proteins were positive acute-phase proteins. Among three proteins other than acute-phase proteins, we confirmed increased levels of antithrombin-III and zinc-α-2-glycoprotein in postsurgical sera by Western blot analysis using other CAS patients’ sera. Furthermore, antithrombin-III and zinc-α-2-glycoprotein were not found among proteins with differential levels in postsurgical and presurgical sera of patients with aortic aneurysms that we identified in a previous study. Conclusions. The results indicated that antithrombin-III and zinc-α-2-glycoprotein would become unique monitoring proteins for evaluating pathophysiological and biochemical processes occurring before and after surgery for CAS. Kazumi Satoh, Kazuo Yamada, Tomoko Maniwa, Teiji Oda, and Ken-ichi Matsumoto Copyright © 2015 Kazumi Satoh et al. All rights reserved. Stability Assessment of Candidate Reference Genes in Urine Sediment of Prostate Cancer Patients for miRNA Applications Wed, 20 May 2015 12:26:45 +0000 http://www.hindawi.com/journals/dm/2015/973597/ We aimed at assessing the stability of candidate reference genes in urine sediments of men subjected to digital rectal examination for suspected prostate cancer (PCa). Two microRNAs (miR-191 and miR-25) and 1 small nucleolar RNA (SNORD48) were assayed in 35 post-DRE urine sediments of men with PCa and in 26 subjects with histologically confirmed benign prostatic hyperplasia (BPH). The stability of candidate reference genes was assessed through BestKeeper algorithm and equivalence test. miR-200b and miR-452 were used to test for the effect of normalization on target genes. Our results proved miR-191 to be the most stable gene, showing the lowest degree of variation and the highest stability value. miR-25 and SNORD48 values fell beyond the cutoff of acceptability. In conclusion, we recommend the use of miR-191 for normalization purposes in post-DRE urine sediments. Maria Giulia Egidi, Giovanni Cochetti, Gabriella Guelfi, Danilo Zampini, Silvana Diverio, Giulia Poli, and Ettore Mearini Copyright © 2015 Maria Giulia Egidi et al. All rights reserved. Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer’s Disease Wed, 20 May 2015 09:46:59 +0000 http://www.hindawi.com/journals/dm/2015/625659/ Alzheimer’s disease (AD) is the most common type of dementia, and promptly diagnosis of AD is crucial for delaying the development of disease and improving patient quality of life. However, AD detection, particularly in the early stages, remains a substantial challenge due to the lack of specific biomarkers. The present study was undertaken to identify and validate the potential of circulating miRNAs as novel biomarkers for AD. Solexa sequencing was employed to screen the expression profile of serum miRNAs in AD and controls. RT-qPCR was used to confirm the altered miRNAs at the individual level. Moreover, candidate miRNAs were examined in the serum samples of patients with mild cognitive impairment (MCI) and vascular dementia (VD). The results showed that four miRNAs (miR-31, miR-93, miR-143, and miR-146a) were markedly decreased in AD patients’ serum compared with controls. Receiver operating characteristic curve analysis demonstrated that this panel of four miRNAs could be used as potential biomarker for AD. Furthermore, miR-93, and miR-146a were significantly elevated in MCI compared with controls, and the panel of miR-31, miR-93 and miR-146a can be used to discriminate AD from VD. We established a panel of four serum miRNAs as a novel noninvasive biomarker for AD diagnosis. Hui Dong, Jialu Li, Lei Huang, Xi Chen, Donghai Li, Tao Wang, Caiyou Hu, Jun Xu, Chunni Zhang, Ke Zen, Shifu Xiao, Qiao Yan, Cheng Wang, and Chen-Yu Zhang Copyright © 2015 Hui Dong et al. All rights reserved. OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data Tue, 19 May 2015 13:41:49 +0000 http://www.hindawi.com/journals/dm/2015/690878/ In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3′UTR mutations, three missense mutations, and a nonsense mutation. Significantly () increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3′UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (). Similarly ~14-fold increased risk was associated with Val159Gly (), ~17-fold with Gly221Arg (), and ~18-fold with Ser326Cys () in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold () increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer. Kashif Ali, Ishrat Mahjabeen, Maimoona Sabir, Humera Mehmood, and Mahmood Akhtar Kayani Copyright © 2015 Kashif Ali et al. All rights reserved. Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon? Tue, 19 May 2015 07:19:43 +0000 http://www.hindawi.com/journals/dm/2015/519638/ The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) . In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels . In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. Andréa Tavares Dantas, Claudia Diniz Lopes Marques, Laurindo Ferreira da Rocha Junior, Mariana Brayner Cavalcanti, Sayonara Maria Calado Gonçalves, Pablo Ramon Gualberto Cardoso, Henrique de Ataide Mariz, Moacyr Jesus Barreto de Melo Rego, Angela Luzia Branco Pinto Duarte, Ivan da Rocha Pitta, and Maira Galdino da Rocha Pitta Copyright © 2015 Andréa Tavares Dantas et al. All rights reserved. Response to: Comment on “Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio: Novel Markers for Diagnosis and Prognosis in Patients with Idiopathic Sudden Sensorineural Hearing Loss” Mon, 18 May 2015 07:26:46 +0000 http://www.hindawi.com/journals/dm/2015/583738/ Young Joon Seo, Junhui Jeong, Jae Young Choi, and In Seok Moon Copyright © 2015 Young Joon Seo et al. All rights reserved. Th1, Th2, and Th17 Cytokine Involvement in Thyroid Associated Ophthalmopathy Mon, 18 May 2015 07:03:01 +0000 http://www.hindawi.com/journals/dm/2015/609593/ To determine serum cytokine profiles in Graves’ disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ (interferon-gamma), TNF-α (tumor necrosis factor-alpha), IL-1α (interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γ and TNF-α were elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis. Jie Shen, Zhangfang Li, Wenting Li, Ying Ge, Min Xie, Meng Lv, Yanfei Fan, Zhi Chen, Defu Zhao, and Yajuan Han Copyright © 2015 Jie Shen et al. All rights reserved. Genome-Wide Scan for Methylation Profiles in Keloids Thu, 14 May 2015 13:38:06 +0000 http://www.hindawi.com/journals/dm/2015/943176/ Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63%) were hypomethylated and 56 (37%) hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation. Lamont R. Jones, William Young, George Divine, Indrani Datta, Kang Mei Chen, David Ozog, and Maria J. Worsham Copyright © 2015 Lamont R. Jones et al. All rights reserved. The Expression of Notch/Notch Ligand, IL-35, IL-17, and Th17/Treg in Preeclampsia Thu, 14 May 2015 12:36:20 +0000 http://www.hindawi.com/journals/dm/2015/316182/ The aim of this study was to examine the interaction of Notch/Notch ligand with Th17/Treg, cytokines IL-35 and IL-17 in cases of preeclampsia (PE). Methods. Peripheral blood was obtained from 42 PE patients and 22 health pregnant women. The mRNA expressions of Notch/Notch ligand, Treg transcription factor FoxP3 and Th17 transcription factor RORγt, EBI3 and P35 (IL-35 two subunits), and IL-17 were determined by qPCR. The serum levels of IL-17 and IL-35 were measured by ELISA. Results. It was observed that the expressions of Foxp3, EBI3, and P35 in PE patients were lower compared with normal pregnancy, whereas the RORγt expression was significantly increased. The results also demonstrated that PE patients exhibited decreased levels of Treg-related cytokine IL-35, whereas IL-17 was significantly increased. PE patients expressed higher levels of Notch receptor (1–4) and Notch ligand of DLL4, whereas Notch ligand of Jagged-1, -2 was much lower. Furthermore, the levels of FoxP3 T cells correlated positively with Jagged-2. In addition, there were positive correlations between the mRNA level of IL-17 and DLL4. Conclusion. Our results indicated that maternal immunological changes may reverse maternal tolerance in PE, and this phenomenon may due to the Th17/Treg imbalance affected by Notch/Notch ligand. Weiping Cao, Xinzhi Wang, Tinmei Chen, Huaying Zhu, Wenlin Xu, Songlan Zhao, Xiaoqing Cheng, and Liangping Xia Copyright © 2015 Weiping Cao et al. All rights reserved. Clinical Implications and Prognostic Values of Prostate Cancer Susceptibility Candidate Methylation in Primary Nonmuscle Invasive Bladder Cancer Wed, 13 May 2015 06:04:22 +0000 http://www.hindawi.com/journals/dm/2015/402963/ DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, an association between prostate cancer susceptibility candidate (PRAC) methylation and genitourinary cancer was proposed. The aim of the present study was to evaluate the association between PRAC methylation status and clinicopathological parameters and prognosis in long-term follow-up primary nonmuscle invasive bladder cancer (NMIBC). The clinical relevance of PRAC methylation was determined in 136 human bladder specimens (eight normal controls [NCs] and 128 primary NMIBCs) using quantitative pyrosequencing analysis. PRAC methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates revealed significant difference in tumor recurrence and progression according to PRAC methylation status (both p < 0.05). Multivariate Cox regression analysis revealed that the PRAC methylation status was a strong predictor of recurrence (hazard ratio [HR], 2.652; p = 0.012) and progression (HR, 9.531; p = 0.035) of NMIBC. Enhanced methylation status of PRAC was positively associated with a high rate of recurrence and progression in NMIBC patients, suggesting that PRAC methylation may be a promising prognostic marker of NMIBC. Young-Won Kim, Hyung-Yoon Yoon, Sung Pil Seo, Sang Keun Lee, Ho Won Kang, Won Tae Kim, Heui Je Bang, Dong Hee Ryu, Seok-Joong Yun, Sang-Cheol Lee, Wun-Jae Kim, and Yong-June Kim Copyright © 2015 Young-Won Kim et al. All rights reserved. Predictive Levels of CD24 in Peripheral Blood Leukocytes for the Early Detection of Colorectal Adenomas and Adenocarcinomas Mon, 11 May 2015 09:48:12 +0000 http://www.hindawi.com/journals/dm/2015/916098/ CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8–83.2%) and 83.8% (95% CI, 74.6–92.7%) and for adenomas 84.2% (95% CI, 60.4–96.4%) and 73.5% (95% CI, 61.4–83.5%), respectively. In the second trial (n = 149), a similar specificity but higher sensitivity was achieved: 80.0% (95% CI, 63.1–91.6%) for CRC and 89.2% (95% CI, 74.6–97%) for adenomas. A simple noninvasive blood test evaluating CD24 levels has high sensitivity and specificity for detecting colorectal adenomas and cancer in patients undergoing colonoscopy at an urban medical center. Larger multicenter studies are warranted to establish the potential of this promising test. Sarah Kraus, Shiran Shapira, Dina Kazanov, Inna Naumov, Menachem Moshkowitz, Erwin Santo, Lior Galazan, Ravit Geva, Einat Shmueli, Aharon Hallack, and Nadir Arber Copyright © 2015 Sarah Kraus et al. All rights reserved. Vitamin D Is a Good Marker for Disease Activity of Rheumatoid Arthritis Disease Sun, 10 May 2015 06:44:37 +0000 http://www.hindawi.com/journals/dm/2015/260725/ Aim. This study was conducted to find out the optimal vitamin D cutoff point in predicting activity of RA disease. Materials and Methods. One hundred and two rheumatoid arthritis Saudi patients of both genders were recruited in this study. Vitamin D as 25-hydroxy-vitamin D [25(OH)D] was measured and serum level less than 20 ng/mL defined as deficient patient. Disease activity was measured based on the disease activity score index of a 28-joint count (DAS28) using serum erythrocyte sedimentation rate levels. Receiver operating characteristic (ROC) curves were used to determine the optimal vitamin D cutoff points for identifying disease activity. Results. It has been observed that vitamin D levels were lower (P < 0.05) in patients with high disease activity. A significant inverse correlation between serum 25(OH)D levels and DAS28 (r = −0.277, P = 0.014) was shown. ROC curves results showed that vitamin D less than 12.3 ng/mL predicted high disease activity, and vitamin D more than 17.9 ng/mL predicted low disease activity, with good sensitivity and accuracy results regarding vitamin D. Conclusion. Study results concluded that vitamin D is a good predictor of RA disease activity in Saudi patients. Firas Sultan Azzeh and Osama Adnan Kensara Copyright © 2015 Firas Sultan Azzeh and Osama Adnan Kensara. All rights reserved. Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis Thu, 07 May 2015 10:53:16 +0000 http://www.hindawi.com/journals/dm/2015/482146/ Objective. MicroRNA-182 (miR-182) exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival. Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs) for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182. Results. In total, 14 studies were included. A high miR-182 expression level predicted a worse outcome with a pooled HR of 2.18 (95% CI: 1.53–3.11) in ten studies related to overall survival (OS), especially in Chinese populations. The results of seven studies evaluating disease-free survival/relapse-free survival/recurrence-free interval/disease-specific survival (DFS/RFS/RFI/DSS) produced a pooled HR of 1.77 (95% CI: 0.91–3.43), which was not statistically significant; however, the trend was positive. When disregarding the DSS from one study, the expression of miR-182 was significantly correlated with DFS/RFS/RFI (pooled HR = 2.52, 95% CI: 1.67–3.79). Conclusions. High miR-182 expression is associated with poor OS and DFS/RFS/RFI in some types of cancers, and miR-182 may be a useful prognostic biomarker for predicting cancer prognosis. However, given the current insufficient relevant data, further clinical studies are needed. Fei Wang, Shanliang Zhong, Haijun Zhang, Wei Zhang, Hongming Zhang, Xue Wu, and Baoan Chen Copyright © 2015 Fei Wang et al. All rights reserved. Monocyte Proteomics Reveals Involvement of Phosphorylated HSP27 in the Pathogenesis of Osteoporosis Thu, 07 May 2015 08:13:49 +0000 http://www.hindawi.com/journals/dm/2015/196589/ Peripheral monocytes, precursors of osteoclasts, have emerged as important candidates for identifying proteins relevant to osteoporosis, a condition characterized by low Bone Mineral Density (BMD) and increased susceptibility for fractures. We employed 4-plex iTRAQ (isobaric tags for relative and absolute quantification) coupled with LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) to identify differentially expressed monocyte proteins from premenopausal and postmenopausal women with low versus high BMD. Of 1801 proteins identified, 45 were differentially abundant in low versus high BMD, with heat shock protein 27 (HSP27) distinctly upregulated in low BMD condition in both premenopausal and postmenopausal categories. Validation in individual samples () using intracellular ELISA confirmed that total HSP27 (tHSP27) as well as phosphorylated HSP27 (pHSP27) was elevated in low BMD condition in both categories (). Further, using transwell assays, pHSP27, when placed in the upper chamber, could increase monocyte migration () and this was additive in combination with RANKL (receptor activator of ligand) placed in the lower chamber (). Effect of pHSP27 in monocyte migration towards bone milieu can result in increased osteoclast formation and thus contribute to pathogenesis of osteoporosis. Overall, this study reveals for the first time a novel link between monocyte HSP27 and BMD. Bhavna Daswani, Manoj Kumar Gupta, Shubhangi Gavali, Meena Desai, Gajanan J. Sathe, Anushree Patil, Priyanka Parte, Ravi Sirdeshmukh, and M. Ikram Khatkhatay Copyright © 2015 Bhavna Daswani et al. All rights reserved. The Value of Circulating Nogo-B for Evaluating Hepatic Functional Reserve in Patients with Cirrhosis Wed, 06 May 2015 09:44:49 +0000 http://www.hindawi.com/journals/dm/2015/419124/ Objective. To examine Nogo-B in liver tissues and plasma of patients with liver cirrhosis and associate them with various clinical parameters. Materials and Methods. Nogo-B protein expression was examined by immunohistochemistry in 24 human fibrotic/cirrhotic liver specimens and 10 healthy controls. We determined plasma Nogo-B levels by enzyme-linked immunosorbent assay in 301 patients with liver cirrhosis and 153 healthy controls, and then analyzed various clinical parameters. Results. Nogo-B was mainly expressed in nonparenchymal cells in the liver and was marked increased in liver with significant fibrosis/cirrhosis compared to controls. Moreover, Metavir F4 showed a higher level of expression than F2. Plasma Nogo-B levels were significantly higher in cirrhotic patients than in healthy controls and were the highest in Child-Pugh class C patients. Plasma Nogo-B levels were positively correlated with Child-Pugh scores. However, there was no relationship between plasma Nogo-B levels and etiology of liver diseases, ALT, AST, platelet counts, and the severity of esophagogastric varices. Conclusions. Nogo-B is mainly expressed in hepatic nonparenchymal cells and is present in plasma. Abnormally high plasma levels of Nogo-B are associated with hepatic cirrhosis and Child-Pugh score, but not correlated with the grade of liver inflammation or portal hypertension. Plasma Nogo-B may be a novel surrogate marker to reflect liver function reserve. Maoyao Wen, Ruoting Men, Zongze Yang, Xuelian Dan, Wenchao Wu, Xiaojing Liu, and Li Yang Copyright © 2015 Maoyao Wen et al. All rights reserved. Expression of Spindle and Kinetochore-Associated Protein 1 Is Associated with Poor Prognosis in Papillary Thyroid Carcinoma Mon, 04 May 2015 07:47:24 +0000 http://www.hindawi.com/journals/dm/2015/616541/ Aim. Spindle and kinetochore-associated protein 1 (SKA1) is one subtype of SKA, whose protein can make spindle microtubules attach steadily to the kinetochore in the middle of mitosis. At present, there are fewer researches on the relationship between SKA1 expression and tumor development. Methods. In this study, immunohistochemical analysis was used to determine the expression of SKA1 in papillary thyroid carcinoma (PTC) and adjacent tissues. We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis to further verify the results. Results. We found that SKA1 expression was significantly higher in PTC tissues than normal adjacent tissues . There existed a significant correlation among a higher SKA1 expression, including lymphoid node , clinical stage , and extrathyroid invasion . Survival analysis showed high SKA1 expression in PTC patients more likely to relapse after surgery. Conclusion. High SKA1 expression is predictive of poor prognosis of PTC, implying that SKA1 may be a promising new target for targeted therapies for PTC. Chao Dong, Xiao-li Wang, and Bin-lin Ma Copyright © 2015 Chao Dong et al. All rights reserved. Ventilatory Efficiency in Children and Adolescents: A Systematic Review Sun, 03 May 2015 16:17:33 +0000 http://www.hindawi.com/journals/dm/2015/546891/ Introduction. The index of ventilatory efficiency (VE/VCO2) obtained by the progressive exercise test has been considered the gold standard in the prognosis of adults with heart failure, but few studies have evaluated this approach in children. Objective. To verify the scientific evidence about the VE/VCO2 in pediatric and adolescents patients. Methods. A systematic literature review was carried out using the key words VE/VCO2, children, and adolescents using the PEDro and PubMed/MedLine databases. Clinical trials published from 1987 to 2014, including children, adolescents, and young adults up to 25 years, addressing the VE/VCO2 index as a method of evaluation, monitoring, and prognosis were considered. Results. Initially, 95 articles were found; 12 were excluded as the title/abstract did not contain the VE/VCO2 index or because they included patients greater than 25 years of age. From the remaining 83, 58 were repeated between the databases. The final sample consisted of 32 studies including healthy children and children with respiratory and other diseases. Conclusion. There are few studies involving cardiorespiratory assessment by ventilatory efficiency. The studies highlight the fact that high VE/VCO2 values are associated with a worse prognosis of patients due to the relationship with the decrease in pulmonary perfusion and cardiac output. Paloma Lopes Francisco Parazzi, Fernando Augusto de Lima Marson, Maria Angela Gonçalves de Oliveira Ribeiro, Camila Isabel Santos Schivinski, and Jose Dirceu Ribeiro Copyright © 2015 Paloma Lopes Francisco Parazzi et al. All rights reserved. Association between Programmed Cell Death 6 Interacting Protein Insertion/Deletion Polymorphism and the Risk of Breast Cancer in a Sample of Iranian Population Sun, 03 May 2015 14:07:55 +0000 http://www.hindawi.com/journals/dm/2015/854621/ It has been suggested that genetic factors contribute to patients’ vulnerability to breast cancer (BC). The programmed cell death 6 interacting protein (PDCD6IP) encodes for a protein that is known to bind to the products of the PDCD6 gene, which is involved in the apoptosis pathway. The aim of this case-control study is to investigate the relationship between the PDCD6IP 15 bp insertion/deletion (I/D) polymorphism (rs28381975) and BC risk in an Iranian population. A total of 491 females, including 266 BC patients and 225 control subjects without cancer, were enrolled into the study. Our findings revealed that the PDCD6IP 15 bp I/D polymorphism decreased the risk of BC in codominant (, 95% –0.65, , I/D versus DD; , 95% –0.88, , I/I versus DD) and dominant (, 95% –0.63, , D/I + I/I versus D/D) tested inheritance models. Also, the PDCD6IP I allele significantly decreased the risk of BC (, 95% –0.78, ) compared to the D allele. Mohammad Hashemi, Javad Yousefi, Seyed Mehdi Hashemi, Shadi Amininia, Mahboubeh Ebrahimi, Mohsen Taheri, and Saeid Ghavami Copyright © 2015 Mohammad Hashemi et al. All rights reserved. Circulating MicroRNA-21 Is a Potential Diagnostic Biomarker in Gastric Cancer Sun, 03 May 2015 13:35:15 +0000 http://www.hindawi.com/journals/dm/2015/435656/ MicroRNA-21 was upexpressed in gastric cancer (GC) indicating that it is a potential diagnostic biomarker for GC. In this study, 50 GC patients and 50 healthy controls were recruited. miR-21 levels in serum and peripheral blood mononuclear cells (PBMCs) were quantified using quantitative real-time PCR. CA199, and CEA were measured using electrochemiluminescence assay. The sensitivity and specificity of circulating miR-21, CA199 and CEA in GC diagnosis, the correlation of circulating miR-21 to clinicopathological features, and the diagnostic value of miR-21 in different GC stages were determined. The levels of miR-21 in both serum and PBMCs increased significantly in GC patients comparing to healthy controls; however, no correlation was observed between circulating miR-21 level and clinicopathological features. The sensitivity and specificity of miR-21 in serum and PBMCs, and CA199 and CEA in GC diagnosis were 88.4%, 79.6%, 81.3%, 73.4%, 60.5%, 55.9%, and 68.6%, 59.3%, respectively. The positive prediction rates of circulating miR-21 in GC stages I to IV were all around 90%, while those of CA199 and CEA were around or less than 50%. Our data suggest circulating miR-21 (both in serum and in PBMCs) can serve as a good biomarker for GC and could be used in diagnosis of early (stage I) and late GC (stage IV). Jianhong Wu, Guangxin Li, Zeyou Wang, Yongliang Yao, Rui Chen, XiongYong Pu, and Jianjun Wang Copyright © 2015 Jianhong Wu et al. All rights reserved. The Role of Power Doppler Ultrasonography as Disease Activity Marker in Rheumatoid Arthritis Sun, 03 May 2015 10:41:19 +0000 http://www.hindawi.com/journals/dm/2015/325909/ Structural damage in rheumatoid arthritis (RA) occurs early if inflammation is not treated promptly. Treatment targeted to reduce inflammation, in particular, that of synovial inflammation in the joints (synovitis), has been recommended as standard treat-to-target recommendations by rheumatologists. The goal is to achieve disease remission (i.e., no disease activity). Several accepted remission criteria have not always equated to the complete absence of true inflammation. Over the last decade, musculoskeletal ultrasonography has been demonstrated to detect subclinical synovitis not appreciated by routine clinical or laboratory assessments, with the Power Doppler modality allowing clinicians to more readily appreciate true inflammation. Thus, targeting therapy to Power Doppler activity may provide superior outcomes compared with treating to clinical targets alone, making it an attractive marker of disease activity in RA. However, more validation on its true benefits such as its benefits to patients in regard to patient related outcomes and issues with standardized training in acquisition and interpretation of power Doppler findings are required. Shaloo Bhasin and Peter P. Cheung Copyright © 2015 Shaloo Bhasin and Peter P. Cheung. All rights reserved. Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma Thu, 30 Apr 2015 14:02:29 +0000 http://www.hindawi.com/journals/dm/2015/282145/ Introduction. Malignant Pleural Mesothelioma (MPM) is a rare disease, even less frequently described in minority patients. We used a large population-based dataset to study the role of race in MPM presentation, treatment, and survival. Methods. All cases of pathologically proven MPM were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Age, sex, diagnosis year, stage, cancer-directed surgery, radiation, and vital status were analyzed according to self-reported race (black or white). Results. There were 13,046 white and 688 black MPM patients (incidence: 1.1 per 100,000 whites; 0.5 per 100,000 blacks; age-adjusted, ). Black patients were more likely to be female, younger, and with advanced stage and less likely to undergo cancer-directed surgery than whites, after adjustment by stage. On multivariable analysis, younger age and having surgery were associated with longer survival for both cohorts; female gender (HR 0.82 (0.77–0.88)) and early stage at diagnosis (HR 0.83 (0.76–0.90)) were predictive of longer survival in white, but not in black, patients. Conclusions. Surgery was associated with improved survival for both black and white MPM patients. However, black patients were less likely to undergo cancer-directed surgery. Increased surgical intervention in MPM black patients with early stage disease may improve their survival. Emanuela Taioli, Andrea S. Wolf, Jacqueline M. Moline, Marlene Camacho-Rivera, and Raja M. Flores Copyright © 2015 Emanuela Taioli et al. All rights reserved. Dynamic Changes, Cut-Off Points, Sensitivity, and Specificity of Laboratory Data to Differentiate Macrophage Activation Syndrome from Active Disease Thu, 30 Apr 2015 14:01:09 +0000 http://www.hindawi.com/journals/dm/2015/424381/ Purpose. To compare the laboratory data and changes in these data between patients with MAS and patients with flare-up of the autoimmune diseases. Methods. In a prospective study, the static laboratory data and dynamic changes in the selected data in 17 consecutive patients with MAS and 53 patients with active disease of SJIA, PJIA, Kawasaki disease, and SLE were compared. The ROC curve analysis was used to evaluate cut-off points, sensitivity, and specificity of the static and dynamic laboratory data to differentiate between MAS and active disease. Results. In the MAS group, the mean CRP3, ALT, AST, total bilirubin, ferritin, LDH, PT, PTT, and INR were significantly higher and the mean WBC2, PMN2, Lymph2, Hgb1, 2, 3, ESR2, serum albumin, and sodium were significantly lower than in control group. Some of the important cut-off points were PLT2 < 209000/microliter, AST > 38.5, ALT > 38, WBC < 8200 × 103/UL, ferritin > 5277 ng/mL. Conclusion. The dynamic changes in some laboratory data, especially PLT, can differentiate between MAS and active disease. The changes in WBC, PMN, and ESR and the levels of the liver enzymes may also be helpful in the early differentiation. Very high levels of ferritin may also help the diagnosis along with other clinical and laboratory signs. Raheleh Assari, Vahid Ziaee, Arash Mirmohammadsadeghi, and Mohammad-Hassan Moradinejad Copyright © 2015 Raheleh Assari et al. All rights reserved. Overexpression of Growth-Related Oncogene-β Is Associated with Tumorigenesis, Metastasis, and Poor Prognosis in Ovarian Cancer Thu, 30 Apr 2015 12:49:27 +0000 http://www.hindawi.com/journals/dm/2015/387382/ Background. Growth-related oncogene- (GRO-) β is a member of the CXC chemokine family, which may mediate various functions, such as attracting neutrophils to sites of inflammation, regulating angiogenesis, and participating in tumorigenesis and progression. However, the expression of GRO-β in ovarian cancer and its relationship to the clinical characteristics of this disease remain poorly understood. Methods. In this study, immunohistochemical analysis using tissue microarray (TMA) was employed to evaluate the expression of GRO-β in ovarian cancer and to contrast expression with normal ovarian epithelial cells and oviduct epithelial cells. Next, we observed the correlation between GRO-β expression and clinicopathological features of ovarian cancer as well as patient outcome. Results. High GRO-β cytoplasmic expression was observed in 55.15% of patients with ovarian cancer, which was related to lymph node or other metastases (), ascites (), and International Federation of Obstetricians and Gynaecologists (FIGO) stage (). Kaplan-Meier survival and Cox regression analysis revealed that high GRO-β expression () and high CA19-9 level () were independent prognostic indicators of poor outcome in ovarian cancer. Conclusions. Overall, high GRO-β expression correlates with poor prognosis and contributes to ovarian cancer tumorigenesis and metastasis. Qing Ye, Xiaolu Zhai, Wei Wang, Shu Zhang, Huijun Zhu, Di Wang, and Chenyi Wang Copyright © 2015 Qing Ye et al. All rights reserved. Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma Wed, 29 Apr 2015 14:08:02 +0000 http://www.hindawi.com/journals/dm/2015/640263/ Aim. Data from The Cancer Genome Atlas (TCGA) show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC). However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC. Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC). Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%, ). ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma) and recurrence (all ). Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (, hazard ratio = 1.635, 95% CI 1.073–2.493) in HNSCC patients. Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC. Hang Yang, Wen-Qi Jiang, Ye Cao, Yong-An Sun, Jing Wei, Xin An, Ying-Chun Zhang, Ming Song, Shu-Sen Wang, Zhong-Yu Yuan, Rou-Jun Peng, Tan-Huan Chen, Li-Ren Li, and Yan-Xia Shi Copyright © 2015 Hang Yang et al. All rights reserved. Serum Enzyme Profiles Differentiate Five Types of Muscular Dystrophy Wed, 29 Apr 2015 12:53:56 +0000 http://www.hindawi.com/journals/dm/2015/543282/ Background. Differentiation among types of muscular dystrophy (MD) has remained challenging. In this retrospective study, we sought to develop a methodology for differentiation of MD types using analysis of serum enzyme profiles. Methods. The serum levels of enzymes from 232 patients, including 120 with DMD, 36 with BMD, 36 with FSHD, 46 with LGMD, and 11 with EDMD, were evaluated. Results. The characteristic profiles of serum enzymes facilitated differentiation of these five types of MD. DMD was characterized by simultaneous elevation of ALT, AST, LDH, and ALP; BMD and LGMD were characterized by elevation of ALT, AST, and LDH; and FSHD and EDMD were characterized by a lack of abnormal serum enzyme levels. We further developed discriminant functions to distinguish BMD and LGMD. For LGMD, LGMD2B patients had significantly higher ALP levels than non-LGMD2B patients ( U/L versus  U/L, resp., ). Conclusions. Our approach enabled the determination of MD subtypes using serum enzyme profiles prior to genetic testing, which will increase the chance a mutation will be found in the first gene analyzed. Yuling Zhu, Huili Zhang, Yiming Sun, Yaqin Li, Langhui Deng, Xingxuan Wen, Huaqiao Wang, and Cheng Zhang Copyright © 2015 Yuling Zhu et al. All rights reserved.