Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Secernin-1 Contributes to Colon Cancer Progression through Enhancing Matrix Metalloproteinase-2/9 Exocytosis Thu, 26 Feb 2015 12:36:38 +0000 http://www.hindawi.com/journals/dm/2015/230703/ Emerging evidence shows that exocytosis plays a key role in tumor development and metastasis. Secernin-1 (SCRN1) is a novel regulator of exocytosis. Our previous work identified SCRN1 as a tumor-associated gene by bioinformatics analysis of transcriptomes. In this study, we demonstrated the aberrant overexpression of SCRN1 at mRNA and protein level in colon cancer. We also revealed that overexpression of SCRN1 was significantly associated with the tumor development and poor prognosis. Experiments in vitro validated that SCRN1 may promote cancer cell proliferation and secretion of matrix metalloproteinase-2/9 (MMP-2/9) proteins to accelerate tumor progression. Shengtao Lin, Tao Jiang, Yang Yu, Huamei Tang, Su Lu, Zhihai Peng, and Junwei Fan Copyright © 2015 Shengtao Lin et al. All rights reserved. Identification of Endogenous Controls for Analyzing Serum Exosomal miRNA in Patients with Hepatitis B or Hepatocellular Carcinoma Thu, 26 Feb 2015 07:14:10 +0000 http://www.hindawi.com/journals/dm/2015/893594/ Serum exosomal microRNAs (miRNAs) have received considerable attention as potential biomarkers for diagnosing cancer. The canonical technique for measuring miRNA transcript levels is reverse transcription quantitative polymerase chain reaction (RT-qPCR). One prerequisite for validating RT-qPCR data is proper normalization with respect to stably expressed endogenous reference genes. However, genes that meet all of the criteria of a control gene for exosomal miRNAs have not yet been identified. To find out the control gene for exosomal miRNAs, we evaluated the expression stability of 11 well-known reference genes in circulating exosomes. In this study, we found that the combination of miR-221, miR-191, let-7a, miR-181a, and miR-26a can be an optimal gene reference set for normalizing the expression of liver-specific miRNAs. This combination enhanced the robustness of the relative quantification analyses. These findings highlight the importance of validating reference genes before quantifying target miRNAs. Furthermore, our findings will improve studies that monitor hepatitis progression and will aid in the discovery of noninvasive biomarkers to diagnose early stage HCC. Yi Li, Liqun Zhang, Fei Liu, Guiming Xiang, Dongneng Jiang, and Xiaoyun Pu Copyright © 2015 Yi Li et al. All rights reserved. Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility Wed, 25 Feb 2015 11:25:05 +0000 http://www.hindawi.com/journals/dm/2015/827941/ Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme , γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, , and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility. Anna Gvozdjáková, Jarmila Kucharská, Jozef Dubravicky, Viliam Mojto, and Ram B. Singh Copyright © 2015 Anna Gvozdjáková et al. All rights reserved. VEGF Overexpression Is a Valuable Prognostic Factor for Non-Hodgkin’s Lymphoma Evidence from a Systemic Meta-Analysis Wed, 25 Feb 2015 06:50:16 +0000 http://www.hindawi.com/journals/dm/2015/786790/ Vascular endothelial growth factor (VEGF) plays a vital role in the progression of Non-Hodgkin’s lymphoma (NHL). Although multiple studies have investigated the relationship between VEGF expression and prognosis of NHL, these studies have yielded conflicting results. Therefore, we performed a meta-analysis to evaluate the role of VEGF in the prognosis of NHL patients. We systematically searched eligible studies from databases and determined that there was a significant correlation between VEGF overexpression and overall survival (HR (hazard ratio) = 1.66, 95% CI: 1.25–2.22, ). Based on subgroup analysis by study location, number of patients, the source of VEGF expression, and study design, we found that VEGF overexpression in surgically resected tissue (HR = 1.95, 95% CI: 1.41–2.69, ), but not in serum (HR = 1.37, 95% CI: 0.96–1.95, ), was associated with poorer prognosis. Additionally, VEGF overexpression did not correlate with performance status, LDH level, IPI score, tumor staging, B symptoms, or NHL relapse. In summary, overexpression of VEGF in lymphoma tissue represents a promising potential prognostic factor in NHL. Jing Yang, Wenlu Li, Xin He, Guofei Zhang, Lan Yue, and Ying Chai Copyright © 2015 Jing Yang et al. All rights reserved. Polymorphisms in the IFNγ, IL-10, and TGFβ Genes May Be Associated with HIV-1 Infection Tue, 24 Feb 2015 17:04:25 +0000 http://www.hindawi.com/journals/dm/2015/248571/ Objective. This study investigated possible associations between the TNFα-308G/A, IFN+874A/T, IL-6-174C/G, IL-10-1082A/G, and TGF-509C/T polymorphisms with HIV-1 infection, in addition to correlation of the polymorphisms with clinical markers of AIDS progression, such as levels of CD4+/CD8+ T lymphocytes and plasma viral load. Methods. A total of 216 individuals who were infected with HIV-1 and on antiretroviral therapy (ART) and 294 individuals from the uninfected control group were analyzed. Results. All individuals evaluated were negative for total anti-HBc, anti-HCV, anti-T. pallidum, and anti-HTLV-1/2. The polymorphisms were identified by PCR-RFLP. Individuals presenting the IFN+874A allele as well as the AA genotype were more frequent in the HIV-1 infected group compared to the control group (), in addition to having lower levels of CD4+ T lymphocytes. The CD8+ T lymphocytes count was significantly lower in individuals with the IL-10-1082 GG genotype. The TGF-509TT genotype was associated with higher plasma viral load. Conclusions. The results suggest that the presence of the IFN+874A allele confers susceptibility to HIV-1 infection and a decrease in the number of CD4+ T lymphocytes. In addition, the genotype associated with high serum levels of TGF may be associated with an increase in plasma viral load. Felipe Bonfim Freitas, Sandra Souza Lima, Rosimar Neris Martins Feitosa, Vânia Nakauth Azevedo, Marluísa de O. Guimarães Ishak, Ricardo Ishak, and Antonio Carlos R. Vallinoto Copyright © 2015 Felipe Bonfim Freitas et al. All rights reserved. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia Tue, 24 Feb 2015 13:22:29 +0000 http://www.hindawi.com/journals/dm/2015/828145/ Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time ( values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated ( values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population ( values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population. Idalia Garza-Veloz, Margarita L. Martinez-Fierro, Jose Carlos Jaime-Perez, Karol Carrillo-Sanchez, Maria Guadalupe Ramos-Del Hoyo, Angel Lugo-Trampe, Augusto Rojas-Martinez, Cesar Homero Gutierrez-Aguirre, Oscar Gonzalez-Llano, Rosario Salazar-Riojas, Alfredo Hidalgo-Miranda, David Gomez-Almaguer, and Rocio Ortiz-Lopez Copyright © 2015 Idalia Garza-Veloz et al. All rights reserved. Polymorphisms rs12998 and rs5780218 in KiSS1 Suppressor Metastasis Gene in Mexican Patients with Breast Cancer Tue, 24 Feb 2015 12:46:11 +0000 http://www.hindawi.com/journals/dm/2015/365845/ Aims. KiSS1 is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along the KiSS-1 gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K) KiSS1 polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC). Results. The rs5780218 polymorphism was individually associated with breast cancer and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared . The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674). Conclusions. Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) in KiSS1 gene must be analyzed in other populations. Edhit Guadalupe Cruz Quevedo, Gabriela Monserrat Mimendi Aguilar, Luis Anselmo Juárez Aguilar, Susan Andrea Gutierrez Rubio, Silvia Esperanza Flores Martínez, Ingrid Patricia Dávalos Rodríguez, José Sánchez Corona, Martha Isabel Torres Morán, Roberto Carlos Rosales Gómez, and María Cristina Morán Moguel Copyright © 2015 Edhit Guadalupe Cruz Quevedo et al. All rights reserved. Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness Tue, 24 Feb 2015 06:50:58 +0000 http://www.hindawi.com/journals/dm/2015/384208/ Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not reflect the presence of sepsis neither in mouse models nor in a large cohort of ICU patients and do not indicate clinical outcome of critically ill patients. Thus miR-223 serum levels should not be used as a biomarker in this setting. Fabian Benz, Frank Tacke, Mark Luedde, Christian Trautwein, Tom Luedde, Alexander Koch, and Christoph Roderburg Copyright © 2015 Fabian Benz et al. All rights reserved. Detection of SNCA and FBN1 Methylation in the Stool as a Biomarker for Colorectal Cancer Mon, 23 Feb 2015 06:33:24 +0000 http://www.hindawi.com/journals/dm/2015/657570/ Aim. We examined the methylation status of SNCA and FBN1 genes in patients’ paired tissue and stool samples for detection of colorectal cancer (CRC). Patients and Methods. 89 DNA tissue samples (normal/cancer) and corresponding stool samples were analyzed in our study. In addition, 30 stool samples were collected as healthy controls. Results. The methylation level of those samples was measured by methylation-specific polymerase chain reaction (MSP). The result shows that compared with the paired controls, both SNCA and FBN1 were significantly hypermethylated in CRC patients in tissue samples (). In the stool samples, hypermethylated SNCA and FBN1 were detected to be significantly higher than that in normal stool samples (). The combined sensitivity of at least one positive among the two markers in stool samples was 84.3%, with a specificity of 93.3%. In addition, our experiment suggested that the positive rates of SNCA and FBN1 in Dukes A stage were significantly higher than that of FOBT (; , resp.). Conclusion. We concluded that methylation testing of SNCA and FBN1 genes in stool sample may offer a good alternative in a simple, promising, and noninvasive detection of colorectal cancer. Wen-han Li, Hao Zhang, Qi Guo, Xuan-di Wu, Zi-sen Xu, Cheng-xue Dang, Peng Xia, and Yong-chun Song Copyright © 2015 Wen-han Li et al. All rights reserved. The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs Sun, 22 Feb 2015 12:22:23 +0000 http://www.hindawi.com/journals/dm/2015/542543/ Background. The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations. Materials and Methods. We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results. Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups. Discussion. The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population. Salma M. Wakil, Cao Nguyen, Nzioka P. Muiya, Editha Andres, Agnieszka Lykowska-Tarnowska, Batoul Baz, Asma I. Tahir, Brian F. Meyer, Grant Morahan, and Nduna Dzimiri Copyright © 2015 Salma M. Wakil et al. All rights reserved. The -844 G>A PAI-1 Polymorphism Is Associated with Acute Coronary Syndrome in Mexican Population Thu, 19 Feb 2015 11:06:19 +0000 http://www.hindawi.com/journals/dm/2015/460974/ Background. Acute coronary syndrome (ACS) has an important impact in public health with high morbidity and mortality. Prothrombotic and proinflammatory states are involved in the pathogenesis of the disease. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of the fibrinolysis and also is part of immune response. The -844 G>A gene polymorphism is related to increased PAI-1 protein levels. The aim of the study is to evaluate the association of -844 G>A PAI-1 polymorphism with ACS. Methods. A total of 646 individuals were recruited from Western Mexico: 350 unrelated healthy subjects and 296 patients with diagnosis of ACS. Results. The most important risk factor in our population was hypertension, followed by smoking. The genetic distribution showed an association of the A allele (, ) and AA genotype (, ) with ACS. The recessive model displayed similar results (, ). As additional finding, we observed significant differences in the genetic distribution of ACS dyslipidemic patients (, ). The A allele and AA genotype of -844 polymorphism of PAI-1 gene are risk factors for ACS. The AA genotype might be associated with the development of dyslipidemia in ACS patients. Ilian Janet García-González, Yeminia Valle, Elena Sandoval-Pinto, Emmanuel Valdés-Alvarado, Angélica Valdez-Haro, José Francisco Muñoz-Valle, Héctor Enrique Flores-Salinas, Luis Eduardo Figuera-Villanueva, Nory Omayra Dávalos-Rodríguez, and Jorge Ramón Padilla-Gutiérrez Copyright © 2015 Ilian Janet García-González et al. All rights reserved. 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” Thu, 19 Feb 2015 09:46:48 +0000 http://www.hindawi.com/journals/dm/2015/745879/ Erdim Sertoglu, Huseyin Kayadibi, and Metin Uyanik Copyright © 2015 Erdim Sertoglu et al. All rights reserved. The Influence of Vitamin D Receptor Genetic Variants on Bone Mineral Density and Osteoporosis in Chinese Postmenopausal Women Tue, 17 Feb 2015 11:00:24 +0000 http://www.hindawi.com/journals/dm/2015/760313/ Growing evidence indicates that the vitamin D receptor (VDR) gene is an important candidate gene for influencing the development of osteoporosis. The aim of the study was to evaluate the potential association between genetic variants of VDR gene and bone mineral density (BMD) and osteoporosis in Chinese postmenopausal women. The study included 970 Chinese postmenopausal women at the postmenopausal osteoporosis (482) and healthy controls (488). The BMD of lumbar spine (L2–4 anterior-posterior view), femoral neck hip, and total hip was evaluated using the Norland XR-46 dual energy X-ray absorptiometry (DEXA). The genotypes of VDR genetic variants were determined by the created restriction site-PCR (CRS-PCR) and confirmed by DNA sequencing methods. Our data indicated that the VDR p.Glicine (Gly)14 alanine (Ala) and p.histidine (His) 305 glutanine (Gln) genetic variants were statistically associated with adjusted femoral neck hip BMD, adjusted lumbar spine BMD, and adjusted total hip BMD ( values < 0.05). Results from this study suggest that the VDR p.Gly14Ala and p.His305Gln genetic variants are significantly associated with BMD decrease in Chinese postmenopausal women and might be used as molecular markers for assessing the risk of BMD and osteoporosis. Wei He, Ming Liu, Xiaonan Huang, Zuhong Qing, and Wei Gao Copyright © 2015 Wei He et al. All rights reserved. Sequence Variants of Peroxisome Proliferator-Activated Receptor-Gamma Gene and the Clinical Courses of Patients with End-Stage Renal Disease Sun, 15 Feb 2015 07:37:00 +0000 http://www.hindawi.com/journals/dm/2015/763459/ Background. PPAR-γ single nucleotide polymorphisms (SNPs) reportedly play an important role in determining metabolic risk among diverse population. Whether PPAR-γ SNPs affect the clinical courses in ESRD patients is unknown. Methods. From a multicenter cohort, we identified 698 patients with prevalent ESRD between 2002 and 2003, and other 782 healthy subjects as control. Two PPAR-γ SNPs, Pro12Ala (rs1801282) and C161T (rs3856806), were genotyped and their association with ESRD was examined. Both groups were prospectively followed until 2007, and the predictability of genotypes for the long-term survival of ESRD patients was analyzed. Results. After multivariable-adjusted regression, GG genotype of Pro12Ala was significantly more likely to associate with ESRD () among patients with non-diabetes-related ESRD. Cox’s proportional hazard regression showed that both Pro12Ala and C161T polymorphisms were significant predictors of mortality in ESRD patients with DM (Pro12Ala: GG versus other genotypes, hazard ratio [HR] <0.01; ; for C161T, CC versus TT genotypes, HR 2.86; ; CT versus TT genotypes, HR 1.93; ). Conclusion. This is the first and largest study to evaluate PPAR-γ SNPs in ESRD patients. Further mechanistic study is needed to elucidate the role of PPAR-γ among ESRD patients. Chia-Ter Chao, Yen-Ching Chen, Chih-Kang Chiang, Jenq-Wen Huang, Fu-Chang Hu, Cheng-Chung Fang, Chen-Chih Chang, and Chung-Jen Yen Copyright © 2015 Chia-Ter Chao et al. All rights reserved. Albumin-to-Alkaline Phosphatase Ratio: A Novel Prognostic Index for Hepatocellular Carcinoma Mon, 09 Feb 2015 09:52:28 +0000 http://www.hindawi.com/journals/dm/2015/564057/ Prognosis of patients with hepatocellular carcinoma (HCC) depends on both tumour extent and hepatic function reserve. Liver function test (LFT) is a basic routine blood test to evaluate hepatic function. We first analysed LFT components and their associated scores in a training cohort of 217 patients who underwent curative surgery to identify LFT parameters with high performance (discriminatory capacity, homogeneity, and monotonicity of gradient). We derived a novel index, albumin-to-alkaline phosphatase ratio (AAPR), which had the highest c-index (0.646) and (24.774) among other liver biochemical parameters. The AAPR was an independent prognostic factor for overall and disease-free survival. The adjusted hazard ratio of death and tumour relapse was 2.36 () and 1.85 (), respectively. The independent prognostic significance of AAPR on top of 5 commonly used and well established staging systems was further confirmed in 2 independent cohorts of patients receiving surgical resection () and palliative therapy (). In summary, the AAPR is a novel index readily derived from a simple low-cost routine blood test and is an independent prognostic indicator for patients with HCC regardless of treatment options. Anthony W. H. Chan, Stephen L. Chan, Frankie K. F. Mo, Grace L. H. Wong, Vincent W. S. Wong, Yue-Sun Cheung, Henry L. Y. Chan, Winnie Yeo, Paul B. S. Lai, and Ka-Fai To Copyright © 2015 Anthony W. H. Chan et al. All rights reserved. Prognostic Utility of Vitamin D in Acute Coronary Syndrome Patients in Coastal Norway Thu, 05 Feb 2015 11:17:17 +0000 http://www.hindawi.com/journals/dm/2015/283178/ Background. An inverse relationship between cardiovascular risk and levels of vitamin D and omega-3 index may exist. Objectives. To evaluate the prognostic utility of serum 25-hydroxyvitamin D [25(OH)D] in 871 patients with suspected acute coronary syndrome (ACS) and to assess the seasonal correlation between 25(OH)D and the omega-3 index in 456 ACS patients from southwestern Norway. Results. In the univariate analysis the hazard ratio (HR) at 2-year follow-up for all-cause mortality in the highest as compared to the lowest quartile of 25(OH)D in the total population was 0.61 (95% confidence interval (CI), 0.37–1.00), . At 7-year follow-up, the corresponding HR for all-cause mortality was 0.66 (95% CI, 0.49–0.90), , and for females alone 0.51 (95% CI, 0.32–0.83), . Quartile survival did not differ in the multivariable analysis, whereas 25(OH)D < 40 nM (<16 ng/mL) was found to be independently related to mortality. Seasonal differences in 25(OH)D, but not for the omega-3 index, were noted, and the two biomarkers were positively correlated, especially during winter-spring; Pearson’s correlation coefficient was 0.358, . Conclusion. Vitamin D levels are related to survival, especially in females, and correlate with the omega-3 index. Patrycja A. Naesgaard, Volker Pönitz, Hildegunn Aarsetoey, Trygve Brügger-Andersen, Heidi Grundt, William S. Harris, Harry Staines, and Dennis W. T. Nilsen Copyright © 2015 Patrycja A. Naesgaard et al. All rights reserved. MTHFR C677T Gene Polymorphism and Head and Neck Cancer Risk: A Meta-Analysis Based on 23 Publications Sat, 31 Jan 2015 11:17:45 +0000 http://www.hindawi.com/journals/dm/2015/681313/ Objective. Conflicting results on the association between MTHFR polymorphism and head and neck cancer (HNC) risk were reported. We therefore performed a meta-analysis to derive a more precise relationship between MTHFR C677T polymorphism and HNC risk. Methods. Three online databases of PubMed, Embase, and CNKI were researched on the associations between MTHFR C677T polymorphism and HNC risk. Twenty-three published case-control studies involving 4,955 cases and 8,805 controls were collected. Odds ratios (ORs) with 95% confidence interval (CI) were used to evaluate the relationship between MTHFR C677T polymorphism and HNC risk. Sensitivity analysis, cumulative analyses, and publication bias were conducted to validate the strength of the results. Results. Overall, no significant association between MTHFR C677T polymorphism and HNC risk was found in this meta-analysis (T versus C: OR = 1.04, 95% CI = 0.92–1.18; TT versus CC: OR = 1.15, 95% CI = 0.90–1.46; CT versus CC: OR = 1.00, 95% CI = 0.85–1.17; CT + TT versus CC: OR = 1.01, 95% CI = 0.87–1.18; TT versus CC + CT: OR = 1.11, 95% CI = 0.98–1.26). In the subgroup analysis by HWE, ethnicity, study design, cancer location, and negative significant associations were detected in almost all genetic models, except for few significant risks that were found in thyroid cancer. Conclusion. This meta-analysis demonstrates that MTHFR C677T polymorphism may not be a risk factor for the developing of HNC. Yu-Ming Niu, Mo-Hong Deng, Wen Chen, Xian-Tao Zeng, and Jie Luo Copyright © 2015 Yu-Ming Niu et al. All rights reserved. In Vitro Sensitivity of Paired Leishmania (Viannia) braziliensis Samples Isolated before Meglumine Antimoniate Treatment and after Treatment Failure or Reactivation of Cutaneous Leishmaniasis Sat, 31 Jan 2015 08:05:56 +0000 http://www.hindawi.com/journals/dm/2015/943236/ This study evaluated the in vitro sensitivity of paired Leishmania braziliensis samples isolated from the same patient before pentavalent antimonial treatment (Sample A) and after treatment failure or cutaneous leishmaniasis reactivation (Sample B) in patients undergoing intralesional administration or injections (5 mgS/kg/d) of meglumine antimoniate. Fourteen samples from 7 patients were studied. After 24 h of drug exposure, 50% lethal dose (LD50) values for promastigotes ranged from 0.37 mg/mL to 5.86 mg/mL for samples obtained before treatment (A) and 0.89 mg/mL to 7.80 mg/mL for samples obtained after treatment (B). After 48 h, LD50 values ranged from 0.37 mg/mL to 5.75 mg/mL and 0.70 mg/mL to 7.68 mg/mL for A and B samples, respectively. After 48 h, LD50 values for amastigotes ranged from 11.7 to 44.3 μg/mL for A samples and 13.7 to 52.7 μg/mL for B samples. Of 7 patients, 1 discontinued treatment and 6 were cured after retreatment with amphotericin B (4 cases) or meglumine antimoniate (2 cases). Overall the B samples had higher LD50 values than A samples; however the difference was not significant. These results do not support the hypothesis that low-dose and intralesional treatments induce selection of resistant parasites in vitro and suggest that other factors may influence therapeutic outcome in patients with poor response to initial treatment. Cibele Baptista, Luciana de Freitas Campos Miranda, Maria de Fátima Madeira, Leonor Laura Pinto Leon, Fátima Conceição-Silva, and Armando de Oliveira Schubach Copyright © 2015 Cibele Baptista et al. All rights reserved. Can Biomarkers Help to Diagnose Early Heart Failure with Preserved Ejection Fraction? Sat, 31 Jan 2015 06:44:55 +0000 http://www.hindawi.com/journals/dm/2015/426045/ Early heart failure with preserved ejection fraction (HFpEF) is a frequent disease, but its diagnosis is difficult and relies mostly on the evidence of left ventricular filling pressure (LVFP) elevation during exercise. Several reports have suggested that natriuretic peptides plasma levels reflect exercise-induced increase in LVFP, but they still have significant limitations. In this context, any new laboratory biomarker that can accurately reflect LVFP elevation during exercise is desirable. Recently, cardiotrophin-1, soluble endoglin, ST2, growth differentiation factor 15, galectin-3, and other new laboratory markers associated with LVFP have emerged. However, the current data on the relationship of these biomarkers and diastolic dysfunction are limited to resting conditions. Therefore, their secretion deserves to be tested under the exercise to determine their potential role in making a diagnosis of early HFpEF. Jaroslav Meluzín and Josef Tomandl Copyright © 2015 Jaroslav Meluzín and Josef Tomandl. All rights reserved. The Prognostic Value of Intermedin in Patients with Breast Cancer Wed, 28 Jan 2015 07:47:37 +0000 http://www.hindawi.com/journals/dm/2015/862158/ This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects using t-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer. Yi-Min Lu, Jian-Bo Zhong, Hai-Yong Wang, Xiong-Fei Yu, and Zhong-Qi Li Copyright © 2015 Yi-Min Lu et al. All rights reserved. Correlation between Sperm Parameters and Protein Expression of Antioxidative Defense Enzymes in Seminal Plasma: A Pilot Study Tue, 27 Jan 2015 08:34:37 +0000 http://www.hindawi.com/journals/dm/2015/436236/ Background. Semen analysis is the cornerstone in the evaluation of male (in)fertility. However, there are men with normal semen tests but with impaired fertilizing ability, as well as fertile men with poor sperm characteristics. Thus, there is rising interest to find novel parameters that will help to predict and define the functional capacity of spermatozoa. Methods. We examined whether there is a correlation between semen parameters (count, progressive motility, and morphology) and protein expression/activity of antioxidative defense enzymes in seminal plasma from 10 normospermic subjects. Results. Sperm progressive motility was in positive correlation with seminal plasma protein expression of both superoxide dismutase (SOD) isoforms (MnSOD and CuZnSOD) and catalase. Also, positive correlation was observed between sperm count and MnSOD protein expression, as well as between sperm morphology and protein expression of catalase in seminal plasma. In contrast, protein expression of glutathione peroxidase was not in correlation with any sperm parameter, while its activity negatively correlated with sperm morphology and motility. Conclusions. These data suggest that evaluation of protein expression of antioxidative defense enzymes in seminal plasma might be of importance in the evaluation of male fertility status and that could be used as an additional biomarker along with classic semen analysis in assessment of semen quality. Biljana Macanovic, Milica Vucetic, Aleksandra Jankovic, Ana Stancic, Biljana Buzadzic, Eliana Garalejic, Aleksandra Korac, Bato Korac, and Vesna Otasevic Copyright © 2015 Biljana Macanovic et al. All rights reserved. Next Generation Sequencing to Determine the Cystic Fibrosis Mutation Spectrum in Palestinian Population Mon, 26 Jan 2015 08:18:02 +0000 http://www.hindawi.com/journals/dm/2015/458653/ An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine. O. Essawi, M. Farraj, K. De Leeneer, W. Steyaert, K. De Pauw, A. De Paepe, K. Claes, T. Essawi, and P. J. Coucke Copyright © 2015 O. Essawi et al. All rights reserved. Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines? Mon, 19 Jan 2015 07:32:36 +0000 http://www.hindawi.com/journals/dm/2015/758314/ Objective. To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue. Methods. Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue 34) and fatigued (CIS20r fatigue 35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs. Results. Similar cytokine levels were observed between MS patients with and without fatigue . Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age. Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS. Trial Registrations. ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628. Arjan Malekzadeh, Wietske Van de Geer-Peeters, Vincent De Groot, Charlotte Elisabeth Teunissen, Heleen Beckerman, and TREFAMS-ACE Study Group Copyright © 2015 Arjan Malekzadeh et al. All rights reserved. High CD133 Expression in the Nucleus and Cytoplasm Predicts Poor Prognosis in Non-Small Cell Lung Cancer Sun, 18 Jan 2015 11:34:56 +0000 http://www.hindawi.com/journals/dm/2015/986095/ Objective. The aim of this study was to investigate the expression of Prominin-1 (CD133) in cancer cells and its potential value as a prognostic indicator of survival in patients with non-small cell lung cancer (NSCLC). Methods. Cancerous tissues and matched normal tissues adjacent to the carcinoma from 239 NSCLC patients were obtained immediately after surgery. Immunohistochemistry of tissue microarrays was used to characterize the expression of CD133 in NSCLC and adjacent tissues. The correlation of CD133 expression with clinical characteristics and prognosis was determined by statistical analysis. Results. CD133 protein expression levels in both the cytoplasm and nucleus were significantly higher in NSCLC tissues compared with corresponding peritumoral tissue (). CD133 expression in the nucleus of NSCLC cells was related to tumor diameter (), tumor differentiation (), and TNM stage (). Kaplan-Meier survival and Cox regression analyses revealed that high CD133 expression in the nucleus was an independent predictor of poor prognosis of NSCLC, as was high cytoplasmic CD133 expression (). Conclusion. Our findings provide the first evidence that high expression of CD133 in both the nucleus and cytoplasm is associated with poor prognosis in NSCLC. Minjie Huang, Huijun Zhu, Jian Feng, Songshi Ni, and Jianfei Huang Copyright © 2015 Minjie Huang et al. All rights reserved. Nasal Potential Difference in Cystic Fibrosis considering Severe CFTR Mutations Thu, 15 Jan 2015 14:16:23 +0000 http://www.hindawi.com/journals/dm/2015/306825/ The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients) (G1), CF patients with classes IV-VI CFTR mutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ2, and Fisher’s exact tests, . No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects. Ronny Tah Yen Ng, Fernando Augusto de Lima Marson, Jose Dirceu Ribeiro, Antonio Fernando Ribeiro, Carmen Silvia Bertuzzo, Maria Angela Gonçalves de Oliveira Ribeiro, Silvana Dalge Severino, and Eulalia Sakano Copyright © 2015 Ronny Tah Yen Ng et al. All rights reserved. Study on the Usefulness of APR Scores from the Viewpoint of Proinflammatory Cytokines Thu, 15 Jan 2015 12:46:11 +0000 http://www.hindawi.com/journals/dm/2015/981981/ Background. Delayed diagnosis and treatment of newborn infection adversely impact outcomes. Clinical laboratory parameters have aimed to obtain the most correct and prompt diagnosis and treatment of this disease. This study simultaneously observed changes over time in APR as well as proinflammatory cytokines and anti-proinflammatory cytokines and aims to clarify usefulness of APR scores. Methods. We evaluated the usefulness of acute phase reactants (APR) in 46 newborns whose serum up to age 7 days had been stored, with comparison of three types (Group I: infection 15, Group F: fetal inflammatory response syndrome 17, and Group C: control 14) of APR-based scores, those of C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), and haptoglobin (Hp), with proinflammatory cytokine levels. APR scores for CRP, AGP, and Hp and the levels of the proinflammatory cytokines IL-1β, IL-6, IL-8, IL-10, and TNFα were determined. Results. The cytokine levels started to increase from age 0 days and then decreased rapidly. The three APR scores, CRP, AG, and Hp, were elevated at age 0 days and then gradually decreased in infection (Group I) and fetal inflammatory response syndrome (Group F). The duration of antibiotic administration according to APR scores was significantly shorter in Group F than in Group I. Conclusion. This study demonstrated APR scores to be more useful for deciding whether antibiotics should be discontinued than proinflammatory cytokine levels. T. Nakamura, D. Hatanaka, T. Yoshioka, S. Yamada, and H. Goto Copyright © 2015 T. Nakamura et al. All rights reserved. Microinflammation Factors in the Common Diseases of the Heart and Kidneys Wed, 14 Jan 2015 11:35:14 +0000 http://www.hindawi.com/journals/dm/2015/470589/ Aim. To determine levels of interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1) in different cardiorenal syndrome (CRS) modalities and to compare findings to some already investigated direct and indirect parameters of inflammation and atherosclerosis. Materials and Methods. Testing involved 114 examinees, divided into control and clinical groups suffering from different modalities and were formed according to the basis of a valid classification for CRS. Results. C-reactive protein (CRP) was significantly higher in all CRSs in comparison to the control group . PAI-1 in CRSs was statistically higher than in the control group. IL-8 was increased in all CRSs, and especially in CRS-5, where no significance was found. PAI-1 correlated with IL-8 in all CRSs, with significant value in CRS-2 and CRS-5. Correlation for PAI-1 and high-density lipoproteins (HDL) was found in CRS-4, while IL-8 was found to be related to CRP level in all CRSs, with significance only in CRS-1 . Conclusions. C-reactive protein, IL-8, and PAI-1 could be useful for clinical differentiation of chronic modalities of CRSs. Inflammation was the most pronounced in CRS-4. Lipid status parameters could be useful for differentiation of CRSs. Furthermore, HDL in chronic primary kidney diseases and triglycerides and total cholesterol in CRS-5 could be valuable. Danijela Tasic, Sonja Radenkovic, Gordana Kocic, Marina Deljanin Ilic, and Aleksandra Ignjatovic Copyright © 2015 Danijela Tasic et al. All rights reserved. Association between BMP4 rs17563 Polymorphism and NSCL/P Risk: A Meta-Analysis Mon, 12 Jan 2015 06:16:23 +0000 http://www.hindawi.com/journals/dm/2015/763090/ Objective. To investigate the association between bone morphogenetic protein 4 (BMP4) rs17563 polymorphism and nonsyndromic cleft lip with or without palate (NSCL/P) risk. Methods. Four online databases were researched and the related publications were collected. Odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship; publication bias, metaregression, and sensitivity analysis were conducted to guarantee the strength of results. Results. Six published case-control studies were collected. Overall, no significant association between BMP4 rs17563 polymorphism and NSCL/P risk was found. It was notable that significant susceptibility on different ethnicity was observed in the stratified analysis. For Chinese population, the BMP4 rs17563 polymorphism was a significantly increased risk for NSCL/P (C versus T: OR = 1.52, 95% CI = 1.28–1.82, , %; CC versus TT: OR = 2.58, 95% CI = 1.74–3.82, , %; TC + CC versus TT: OR = 1.45, 95% CI = 1.14–1.84, , %; CC versus TT + TC: OR=2.46, 95% CI = 1.46–4.14, , %). On the contrary, significantly protective effects were found in Brazilian population (C versus T: OR = 0.69, 95% CI = 0.50–0.96, , %; TC versus TT: OR = 0.52, 95% CI = 0.40–0.68, , %; TC + CC versus TT: OR = 0.52, 95% CI = 0.35–0.78, , %). Conclusion. This meta-analysis indicated that BMP4 rs17563 polymorphism could play a different role during the development of NSCL/P based on ethnicity diversity. Yuan-Yuan Hu, Chuan-Qi Qin, Mo-Hong Deng, Yu-Ming Niu, and Xing Long Copyright © 2015 Yuan-Yuan Hu et al. All rights reserved. Validation of Serum Biomarkers Derived from Proteomic Analysis for the Early Screening of Preeclampsia Mon, 05 Jan 2015 09:30:59 +0000 http://www.hindawi.com/journals/dm/2015/121848/ Aim. To examine the potential value of previously identified biomarkers using proteomics in early screening for preeclampsia (PE). Methods. 24 blood samples from women who subsequently developed PE and 48 from uncomplicated pregnancies were obtained at 11–13 weeks and analysed after delivery. Cystatin-C, sVCAM-1, and Pappalysin-1 were quantified by ELISA. Maternal characteristics and medical history were recorded. Results. Median values of Cystatin-C, sVCAM-1, and Pappalysin-1 in the PE group as compared to controls were 909.1 gEq/mL versus 480.0 gEq/mL, , 832.0 gEq/mL versus 738.8 gEq/mL, , and 234.4 gEq/mL versus 74.9 gEq/mL, , respectively. Areas under the receiver-operating characteristic curves (AUC, standard error (SE)) for predicting PE were Cystatin-C: 0.90 (SE 0.04), VCAM-1: 0.66 (SE 0.074), and Pappalysin-1: 0.63 (SE 0.083). To discriminate between cases at risk for PE and normal controls, cut-off values of 546.8 gEq/mL for Cystatin-C, 1059.5 gEq/mL for sVCAM-1, and 220.8 gEq/mL for Pappalysin-1 were chosen, providing sensitivity of 91%, 41%, and 54% and specificity of 85%, 100%, and 95%, respectively. Conclusions. sVCAM-1 and Pappalysin-1 do not improve early screening for PE. Cystatin-C, however, seems to be associated with subsequent PE development, but larger studies are necessary to validate these findings. Aggeliki Kolialexi, Dimitrios Gourgiotis, George Daskalakis, Antonis Marmarinos, Alexandra Lykoudi, Danai Mavreli, Ariadni Mavrou, and Nikolas Papantoniou Copyright © 2015 Aggeliki Kolialexi et al. All rights reserved. High Frequency of CD8 Positive Lymphocyte Infiltration Correlates with Lack of Lymph Node Involvement in Early Rectal Cancer Tue, 30 Dec 2014 09:47:13 +0000 http://www.hindawi.com/journals/dm/2014/792183/ Aims. A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. Methods. A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2) was stained for several immunomarkers of the innate and the adaptive immune response. Patients’ survival and nodal status were analyzed and correlated with infiltration of the different immune cells. Results. Of all tested markers, only CD8 () and TIA-1 () were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect “per se,” CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992–0.996; and OR 0.988; 95% CI 0.984–0.994; , resp.). An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (). Conclusion. Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients’ nodal involvement. Silvio Däster, Serenella Eppenberger-Castori, Christian Hirt, Inti Zlobec, Tarik Delko, Christian A. Nebiker, Savas D. Soysal, Francesca Amicarella, Giandomenica Iezzi, Giuseppe Sconocchia, Michael Heberer, Alessandro Lugli, Giulio C. Spagnoli, Christoph Kettelhack, Luigi Terracciano, Daniel Oertli, Urs von Holzen, Luigi Tornillo, and Raoul A. Droeser Copyright © 2014 Silvio Däster et al. 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