Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Correlation of Serum β-Endorphin and the Quality of Life in Allergic Rhinitis Thu, 25 Aug 2016 16:13:48 +0000 http://www.hindawi.com/journals/dm/2016/2025418/ Background. Allergic rhinitis (AR) significantly impairs the quality of life of the patients; however, a questionnaire alone is an insufficient and subjective measure of this condition. Obtaining an objective clinical assessment of the level of impairment will be valuable for its treatment. β-Endorphin is one of the most important mediators of both mental state and specific immunity. Thus, we investigated the possibility of using β-endorphin as a biomarker for evaluating the impairment level in AR. Methods. This study included 48 patients with AR and 32 healthy volunteers. The serum β-endorphin level was determined by enzyme immunoassay, and the serum-specific IgE and total IgE levels were determined by immunoblot assay. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to assess the impairment level in the symptom duration. Results. The β-endorphin concentration was significantly decreased in AR patients compared to the healthy controls (, ). There was significant negative correlation between the impairment level and serum β-endorphin level (correlation coefficient: 0.468; ; ), but there was no association between the serum β-endorphin and total IgE levels (, ). Conclusion. -Endorphin is a systemic biomarker that has the potential to assess the impairment level in AR and may therefore be a novel therapeutic target for the treatment of AR. Jichao Sha, Cuida Meng, Lin Li, Na Cui, Qian Xiu, and Dongdong Zhu Copyright © 2016 Jichao Sha et al. All rights reserved. CEACAM1: Expression and Role in Melanocyte Transformation Wed, 24 Aug 2016 18:00:21 +0000 http://www.hindawi.com/journals/dm/2016/9406319/ Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination. Gabriela Turcu, Roxana Ioana Nedelcu, Daniela Adriana Ion, Alice Brînzea, Mirela Daniela Cioplea, Lucia Beatrice Jilaveanu, and Sabina Andrada Zurac Copyright © 2016 Gabriela Turcu et al. All rights reserved. The Role of Fecal Calprotectin in Evaluating Intestinal Involvement of Behçet’s Disease Wed, 24 Aug 2016 06:11:23 +0000 http://www.hindawi.com/journals/dm/2016/5423043/ One of the regions of involvement of Behçet’s disease (BD), a systematic inflammatory vasculitis with unknown etiology, is the gastrointestinal (GI) tract. Upper GI endoscopy, colonoscopy, and capsule endoscopy are frequently used methods to diagnose the intestinal involvement of BD. The aim of this study was to investigate the role of fecal calprotectin (FC) in the evaluation of intestinal involvement in BD. Material and Method. A total of 30 patients who were diagnosed with BD and had no GI symptoms and 25 individuals in the control group were included in this study. Results. Levels of FC were statistically significantly higher in patients with BD compared to the control group (). The correlation analysis performed including FC and markers of disease activity revealed a positive and statistically significant correlation between FC level and CRP and erythrocyte sedimentation rate (: 0.255, , and : 0.404, , resp.). FC levels in patients who were detected to have ulcers in the terminal ileum and colon in the colonoscopic examination were statistically significantly higher compared to the patients with BD without intestinal involvement (). Conclusion. The measurement of FC levels, in patients with BD who are asymptomatic for GI involvement, may be helpful to detect the possible underlying intestinal involvement. Burak Özşeker, Cem Şahin, Havva Solak Özşeker, S. Cumali Efe, Taylan Kav, and Yusuf Bayraktar Copyright © 2016 Burak Özşeker et al. All rights reserved. From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers Tue, 23 Aug 2016 14:21:41 +0000 http://www.hindawi.com/journals/dm/2016/4517492/ Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies. Vlad Voiculescu, Bogdan Calenic, Mihaela Ghita, Mihai Lupu, Ana Caruntu, Liliana Moraru, Suzana Voiculescu, Alexandra Ion, Maria Greabu, Nikolay Ishkitiev, and Constantin Caruntu Copyright © 2016 Vlad Voiculescu et al. All rights reserved. miR-155 Inhibits Nucleus Pulposus Cells’ Degeneration through Targeting ERK 1/2 Thu, 18 Aug 2016 08:30:47 +0000 http://www.hindawi.com/journals/dm/2016/6984270/ We first investigated the difference in microRNA expression between normal NP cells and degenerative NP cells using gene chip. We have found that the expression of ERK1/2 was decreased with overexpression of miR-155 in normal nucleus pulposus cell. Expression of ERK1/2 was increased with inhibition of miR-155. Overexpression or inhibition of miR-155 had no effects on the expression level of mRNA ERK1/2 in nucleus pulposus cell, which showed that miR-155 affected the expression of pERK1/2 after transcription of ERK1/2 mRNA indicating that ERK1/2 was a new target protein regulated by miR-155. In the degeneration of intervertebral disc, inhibited miR-155 decreased the expressions of extracellular main matrix collagen II and glycosaminoglycan and increased expression of ERK1/2. Taken together, our data suggested that miR-155 was the identified miRNA which regulated NP cells degenerated through directly targeting ERK1/2. Dongping Ye, Libing Dai, Yicun Yao, Shengnan Qin, Han Xie, Wen Wang, and Weiguo Liang Copyright © 2016 Dongping Ye et al. All rights reserved. Detection of Soluble ED-A+ Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling Thu, 18 Aug 2016 07:44:00 +0000 http://www.hindawi.com/journals/dm/2016/3695454/ Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, ) and dilated (DCM, ) cardiomyopathy as well as hypertensive heart disease (HHD, ) compared to healthy controls (). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (), a negative correlation with left ventricular ejection fraction (, : −0.353), a positive correlation with left atrial diameter (, : 0.431), and a strong positive correlation with systolic pulmonary artery pressure (, : 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn. Barbara Ziffels, Johanna Ospel, Katja Grün, Dario Neri, Alexander Pfeil, Michael Fritzenwanger, Hans R. Figulla, Christian Jung, Alexander Berndt, and Marcus Franz Copyright © 2016 Barbara Ziffels et al. All rights reserved. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications Thu, 18 Aug 2016 06:44:05 +0000 http://www.hindawi.com/journals/dm/2016/1987505/ Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly () overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. Maciej Tarnowski, Michał Czerewaty, Anna Deskur, Krzysztof Safranow, Wojciech Marlicz, Elżbieta Urasińska, Mariusz Z. Ratajczak, and Teresa Starzyńska Copyright © 2016 Maciej Tarnowski et al. All rights reserved. Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery Sun, 14 Aug 2016 11:53:35 +0000 http://www.hindawi.com/journals/dm/2016/1868739/ Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients ( years old, 117 men and 14 women) with left ventricular ejection fraction of and low logistic EuroScore () undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11–24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), ]. OPN levels were positively related to EuroScore (, ). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event () and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43–4.99), ]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome. Eftihia Sbarouni, Panagiota Georgiadou, Sofia Chatzikyriakou, Antonis Analitis, Antigoni Chaidaroglou, Demitris Degiannis, and Vassilis Voudris Copyright © 2016 Eftihia Sbarouni et al. All rights reserved. Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study Thu, 11 Aug 2016 13:15:49 +0000 http://www.hindawi.com/journals/dm/2016/4095723/ Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer’s disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy. Oleg A. Levada, Nataliya V. Cherednichenko, Andriy V. Trailin, and Alexandra S. Troyan Copyright © 2016 Oleg A. Levada et al. All rights reserved. GSTP1 Methylation and Protein Expression in Prostate Cancer: Diagnostic Implications Wed, 10 Aug 2016 13:23:49 +0000 http://www.hindawi.com/journals/dm/2016/4358292/ GSTP1 belongs to the GSTs family, a group of enzymes involved in detoxification of exogenous substances and it also plays an important role in cell cycle regulation. Its dysregulation correlates with a large variety of tumors, in particular with prostate cancer. We investigated GSTP1 methylation status with methylation specific PCR (MS-PCR) in prostate cancer (PCa) and in benign tissue of 56 prostatectomies. We also performed immunohistochemistry (IHC) so as to correlate gene methylation with gene silencing. GSTP1 appears methylated in PCa and not in healthy tissue; IHC confirmed that methylation leads to protein underexpression (). GSTP1 is highly expressed in basal cell layer and luminal cells in benign glands while in prostatic intraepithelial neoplasia (PIN) it stains only basal cell layer, whereas PCa glands are completely negative. We demonstrated that methylation leads to underexpression of GSTP1. The progressive loss of GSTP1 expression from healthy glands to PIN and to PCa glands underlines its involvement in early carcinogenesis. Filippo Martignano, Giorgia Gurioli, Samanta Salvi, Daniele Calistri, Matteo Costantini, Roberta Gunelli, Ugo De Giorgi, Flavia Foca, and Valentina Casadio Copyright © 2016 Filippo Martignano et al. All rights reserved. Oxidative Stress-Related Biomarkers in Postmenopausal Osteoporosis: A Systematic Review and Meta-Analyses Wed, 10 Aug 2016 11:45:51 +0000 http://www.hindawi.com/journals/dm/2016/7067984/ Numerous studies suggested that oxidative stress (OS) played a central role in the onset and development of postmenopausal osteoporosis (PO); however, conflicting results were obtained as to the association of OS-related biomarkers and PO. This meta-analysis aimed to identify the association between these markers and PO, and explore factors that may explain the inconsistencies in these results. A systematic literature search was conducted in relevant database. Search terms and selection criteria were priorly determined to identify and include all studies that detected markers of OS in PO patients. We pooled data with a random effects meta-analysis with standardized mean differences and 95% confidence interval. Total 17 studies including 12 OS markers were adopted. The results showed that superoxide dismutase (SOD) in erythrocytes, catalase (CAT), total antioxidant status (TAS), hydroperoxides (HY), advanced oxidation protein products (AOPP), malondialdehyde (MDA), and vitamin B12 (VB12) in plasma/serum were not statistically different between the PO and control group, whereas significantly increased level of homocysteine (Hcy) and nitric oxide (NO), along with decreased SOD, glutathione peroxidase (GPx), folate, and total antioxidant power (TAP) in plasma/serum were obtained in the PO group. In summary, OS might serve as potential biomarkers in the etiopathophysiology and clinical course of PO. Qiaozhen Zhou, Li Zhu, Dafeng Zhang, Ning Li, Qiao Li, Panpan Dai, Yixin Mao, Xumin Li, Jianfeng Ma, and Shengbin Huang Copyright © 2016 Qiaozhen Zhou et al. All rights reserved. New Progress of Epigenetic Biomarkers in Urological Cancer Tue, 09 Aug 2016 12:58:58 +0000 http://www.hindawi.com/journals/dm/2016/9864047/ Urological cancers consist of bladder, kidney, prostate, and testis cancers and they are generally silenced at their early stage, which leads to the loss of the best opportunity for early diagnosis and treatment. Desired biomarkers are scarce for urological cancers and current biomarkers are lack of specificity and sensitivity. Epigenetic alterations are characteristic of nearly all kinds of human malignances including DNA methylation, histone modification, and miRNA regulation. Besides, the detection of these epigenetic conditions is easily accessible especially for urine, best target for monitoring the diseases of urinary system. Here, we summarize some new progress about epigenetic biomarkers in urological cancers, hoping to provide new thoughts for the diagnosis, treatment, and prognosis of urological cancers. Peng Wu, Ziyi Cao, and Song Wu Copyright © 2016 Peng Wu et al. All rights reserved. Urinary Lysosomal Enzyme Activities and Albuminuria in Ghanaian Patients with Type 2 Diabetes Mellitus Tue, 09 Aug 2016 08:23:46 +0000 http://www.hindawi.com/journals/dm/2016/2810639/ Renal tubular lysosomal enzyme activities like alanine aminopeptidase (AAP) and N-acetyl--D-glucosaminidase (NAG) have been shown to increase in patients developing diabetic nephropathy and nephrosclerosis. This study aimed to determine the activities of N-acetyl--D-glucosaminidase and alanine aminopeptidase and albumin concentration in urine samples of patients with type 2 diabetes. One hundred and thirty (65 type 2 diabetic and 65 nondiabetic) subjects participated in this study. Blood samples were drawn for measurements of fasting blood glucose, albumin (Alb), lipids, and creatinine (Cr). Early morning spot urine samples were also collected for activities of alanine aminopeptidase (AAP), N-acetyl--D-glucosaminidase (NAG), and concentration of albumin (U-Alb) and creatinine (U-Cr). Both NAG/Cr and AAP/Cr were significantly increased in diabetic subjects compared to controls (). There was positive correlation between NAG/Cr and Alb/Cr (, ) and between NAG/Cr and serum creatinine (, ). A negative correlation was found between NAG/Cr and eGFR (, ). 9.3% and 12% of diabetics with normoalbuminuria had elevated levels of AAP/Cr and NAG/Cr, respectively. We conclude that measuring the urinary enzymes activities (NAG/Cr and AAP/Cr) could be useful as a biomarker of early renal involvement in diabetic complications. Henry Asare-Anane, Felix Twum, Emmanuel Kwaku Ofori, Erving L. Torgbor, Seth D. Amanquah, and Charlotte Osafo Copyright © 2016 Henry Asare-Anane et al. All rights reserved. Expression Pattern and Clinicopathological Relevance of the Indoleamine 2,3-Dioxygenase 1/Tryptophan 2,3-Dioxygenase Protein in Colorectal Cancer Mon, 08 Aug 2016 16:26:17 +0000 http://www.hindawi.com/journals/dm/2016/8169724/ Aims. Cancer cells use the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to suppress the host’s immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. Higher IDO1 expression was shown to be involved in colorectal cancer (CRC) progression and to be correlated with impaired clinical outcome. However, the potential correlation between the expression of IDO1 in a CRC population with a low mutation rate of the APC gene remains unknown. Material and Methods. Tissues and blood samples were collected from 192 CRC patients. The expressions of IDO1, tryptophan 2,3-dioxygenase (TDO2), and beta-catenin proteins were analyzed by immunohistochemistry. Microsatellite instability (MSI) was determined by PCR amplification of microsatellite loci. Results. The results showed that high IDO1 or TDO2 protein expression was associated with characteristics of more aggressive phenotypes of CRC. For the first time, they also revealed a positive correlation between the abnormal expression of beta-catenin and IDO1 or TDO2 proteins in a CRC population with a low mutation rate of APC. Conclusion. We concluded that an IDO1-regulated molecular pathway led to abnormal expression of beta-catenin in the nucleus/cytoplasm of CRC patients with low mutation rate of APC, making IDO1 an interesting target for immunotherapy in CRC. I-Chien Chen, Kuen-Haur Lee, Ying-Hua Hsu, Wei-Ran Wang, Chuan-Mu Chen, and Ya-Wen Cheng Copyright © 2016 I-Chien Chen et al. All rights reserved. Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma Mon, 08 Aug 2016 10:52:10 +0000 http://www.hindawi.com/journals/dm/2016/9831237/ Basal cell carcinoma (BCC) is the world’s leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC. Mihai Lupu, Constantin Caruntu, Mihaela Adriana Ghita, Vlad Voiculescu, Suzana Voiculescu, Adrian E. Rosca, Ana Caruntu, Liliana Moraru, Iris Maria Popa, Bogdan Calenic, Maria Greabu, and Daniela Elena Costea Copyright © 2016 Mihai Lupu et al. All rights reserved. Expression Profile of p53 and p21 in Large Bowel Mucosa as Biomarkers of Inflammatory-Related Carcinogenesis in Ulcerative Colitis Sun, 07 Aug 2016 09:59:18 +0000 http://www.hindawi.com/journals/dm/2016/3625279/ Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that slightly increases the risk of colorectal cancer in patients with long-standing extended disease. Overexpression of p53 and p21 in colonic epithelia is usually detected in UC patients when no dysplasia is histologically seen and it is used by pathologists as a discriminator between regenerative changes and intraepithelial neoplasia, as well as a tissue biomarker useful to predict the risk of evolution toward malignancy. We present a one-year prospective observational study including a cohort of 45 patients with UC; p53 and p21 were evaluated in epithelial cells. p53 was positive in 74 samples revealed in 5% to 90% of epithelial cells, while 63 biopsies had strong positivity for p21 in 5% to 50% of epithelial cells. Architectural distortion was significantly correlated with p53 overexpression in epithelial cells. Thus, we consider that architectural distortion is a good substitute for p53 and p21 expression. We recommend use of p53 as the most valuable tissue biomarker in surveillance of UC patients, identifying the patients with higher risk for dysplasia. Association of p21 is also recommended for a better quantification of risk and for diminishing the false-negative results. Cristiana Popp, Luciana Nichita, Theodor Voiosu, Alexandra Bastian, Mirela Cioplea, Gianina Micu, Gabriel Pop, Liana Sticlaru, Andreea Bengus, Andrei Voiosu, and Radu Bogdan Mateescu Copyright © 2016 Cristiana Popp et al. All rights reserved. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus Wed, 03 Aug 2016 14:05:36 +0000 http://www.hindawi.com/journals/dm/2016/1243819/ Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus. Catalina Ionescu, Catalina Gabriela Corbu, Cristiana Tanase, Christian Jonescu-Cuypers, Cristina Nicula, Dana Dascalescu, Miruna Cristea, and Liliana-Mary Voinea Copyright © 2016 Catalina Ionescu et al. All rights reserved. Elevated Plasma α-Defensins (HNP1–3) Levels Correlated with IgA1 Glycosylation and Susceptibility to IgA Nephropathy Tue, 02 Aug 2016 06:19:50 +0000 http://www.hindawi.com/journals/dm/2016/8123138/ Aim. IgA nephropathy (IgAN) is the most common form of glomerulonephritis. Recent genome-wide association study (GWAS) suggested that DEFA locus (which encodes α-defensins) may play a key role in IgAN. Methods. The levels of α-defensins in 169 IgAN patients and 83 healthy controls were tested by ELISA. Results. We observed that α-defensins human neutrophil peptides 1–3 (HNP1–3) in IgAN patients were elevated compared with healthy controls. The mean levels of α-defensins of 83 healthy controls and 169 IgAN patients were 50 ng/mL and 78.42 ng/mL. When the results were adjusted to the mean levels of α-defensins of IgAN patients, the percentage of individuals with high levels of α-defensins increased in IgAN patients (22.5%) compared to healthy controls (9.6%) (). The elevation of α-defensins in IgAN patients was independent of renal function or neutrophil count, which were major sources of α-defensins in circulation. More importantly, negative correlation was observed between galactose-deficient IgA1and α-defensins. Conclusion. As α-defensin is a lectin-like peptide, we speculated that it might be involved in IgA galactose deficiency. The data implied that patients with IgAN had higher plasma α-defensins levels and high α-defensins correlated with IgA galactose deficiency, further suggesting a pathogenic role of α-defensins in IgAN. Yuan-yuan Qi, Xu-jie Zhou, Fa-juan Cheng, and Hong Zhang Copyright © 2016 Yuan-yuan Qi et al. All rights reserved. Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients Sun, 31 Jul 2016 11:54:54 +0000 http://www.hindawi.com/journals/dm/2016/3672353/ Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects ( and , resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (, ), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process. Alessandro Trentini, Massimiliano Castellazzi, Carlo Cervellati, Maria Cristina Manfrinato, Carmine Tamborino, Stefania Hanau, Carlo Alberto Volta, Eleonora Baldi, Vladimir Kostic, Jelena Drulovic, Enrico Granieri, Franco Dallocchio, Tiziana Bellini, Irena Dujmovic, and Enrico Fainardi Copyright © 2016 Alessandro Trentini et al. All rights reserved. Predictors of Impaired Postpartum Renal Function in Women after Preeclampsia: Results of a Prospective Single Center Study Sun, 31 Jul 2016 07:27:12 +0000 http://www.hindawi.com/journals/dm/2016/7861919/ Objective. The purpose of this prospective study was to investigate the predictive value of single prepartum findings combined with serum biomarkers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor) indicating severity of preeclampsia (PE) for occurrence and extent of impaired postpartum kidney function. Study Design. In this prospective, single center study 44 PE patients were compared to 39 healthy controls (similar in age and gestational age with singleton pregnancy) evaluated at time of delivery and at 6 months and 12 months postpartum. values below 0.05 are considered statistically significant. Results. The majority of the PE patients had persistence of proteinuria (>120 mg/L after delivery) 6 months () and 12 months postpartum () compared to controls. Also reduced GFR (glomerular filtration rate) persisted up to 6 months postpartum in PE patients compared to controls (). Prepartum sFlt-1 levels indeed correlated with impaired renal function parameters. Conclusion. A significant proportion of our PE patients had lower GFR levels and persistent proteinuria up to 12 months postpartum. Prepartum sFlt-1 is a trend-setting marker for impaired renal function postpartum, but it is not sufficient enough to predict renal impairment after PE. An evaluation of 24-month follow-up data is scheduled. T. Kaleta, A. Stock, D. Panayotopoulos, O. Vonend, D. Niederacher, M. Neumann, T. Fehm, W. Kaisers, and M. Fleisch Copyright © 2016 T. Kaleta et al. All rights reserved. Expressions of Endocan in Patients with Meningiomas and Gliomas Wed, 27 Jul 2016 06:44:27 +0000 http://www.hindawi.com/journals/dm/2016/7157039/ Objective. Endocan has been shown to be a marker for several cancers and may show degree of malignancy. The aim of this study is to assess tissue levels of endocan in common brain tumors, namely, meningiomas, low-grade gliomas (LGGs), and high-grade gliomas (HGGs). Patients and Methods. Endocan was assayed by commercially available enzyme linked immunosorbent assay (ELISA) kits in a total of 50 brain tumors (20 meningiomas, 19 LGGs, and 20 HGGs) and 15 controls. The results were compared to control brain tissues. Results. Each tumor group showed significant higher levels of endocan compared to controls (). In addition, endocan levels showed steady increase from the least (meningiomas) to the most (HGGs) malignant tumors and positive correlation was noted between the degree of malignancy and endocan level (). Conclusion. Endocan, a vital molecule for angiogenesis, is expressed in common brain tumors and results suggest that endocan could be a marker for malignancy. Pinar Atukeren, Ahmad Kunbaz, Okan Turk, Rahsan Kemerdere, Mustafa Onur Ulu, Nursel Turkmen Inanir, and Taner Tanriverdi Copyright © 2016 Pinar Atukeren et al. All rights reserved. Tyrosine Kinase Receptor Landscape in Lung Cancer: Therapeutical Implications Tue, 26 Jul 2016 13:26:10 +0000 http://www.hindawi.com/journals/dm/2016/9214056/ Lung cancer is a heterogeneous disease responsible for the most cases of cancer-related deaths. The majority of patients are clinically diagnosed at advanced stages, with a poor survival rate. For this reason, the identification of oncodrivers and novel biomarkers is decisive for the future clinical management of this pathology. The rise of high throughput technologies popularly referred to as “omics” has accelerated the discovery of new biomarkers and drivers for this pathology. Within them, tyrosine kinase receptors (TKRs) have proven to be of importance as diagnostic, prognostic, and predictive tools and, due to their molecular nature, as therapeutic targets. Along this review, the role of TKRs in the different lung cancer histologies, research on improvement of anti-TKR therapy, and the current approaches to manage anti-TKR resistance will be discussed. A. Quintanal-Villalonga, Luis Paz-Ares, Irene Ferrer, and S. Molina-Pinelo Copyright © 2016 A. Quintanal-Villalonga et al. All rights reserved. Evaluation of MTBDRplus and MTBDRsl in Detecting Drug-Resistant Tuberculosis in a Chinese Population Mon, 25 Jul 2016 13:37:17 +0000 http://www.hindawi.com/journals/dm/2016/2064765/ Background. This study aims to evaluate GenoType MTBDRplus and GenoType MTBDRsl for their ability to detect drug-resistant tuberculosis in a Chinese population. Methods. We collected 112 Mycobacteria tuberculosis strains from Jiangsu province, China. The conventional DST and line probe assay were used to detect drug resistance to rifampicin (RFP), isoniazid (INH), ofloxacin (OFX), kanamycin (Km), and ethambutol (EMB). Results. The sensitivity and specificity were 100% and 50% for RFP and 86.11% and 47.06% for INH, respectively. The most common mutations observed in MTBDRplus were rpoBWT8 omission + MUT3 presence, katGWT omission + MUT1 presence, and inhAWT1 omission + MUT1 presence. For drug resistance to OFX, Km, and EMB, the sensitivity of MTBDRsl was 94.74%, 62.50%, and 58.82%, respectively, while the specificity was 92.59%, 98.81%, and 91.67%, respectively. The most common mutations were gyrAWT3 omission + MUT3C presence, rrsMUT1 presence, embBWT omission + MUT1B presence, and embBWT omission + MUT1A presence. Sequencing analysis found several uncommon mutations. Conclusion. In combination with DST, application of the GenoType MTBDRplus and GenoType MTBDRsl assays might be a useful additional tool to allow for the rapid and safe diagnosis of drug resistance to RFP and OFX. Wei Lu, Yan Feng, Jianming Wang, and Limei Zhu Copyright © 2016 Wei Lu et al. All rights reserved. Circulating MicroRNAs as Potential Molecular Biomarkers in Pathophysiological Evolution of Pregnancy Sun, 17 Jul 2016 08:35:41 +0000 http://www.hindawi.com/journals/dm/2016/3851054/ MicroRNAs represent nonprotein coding small RNA molecules that are very stable to degradation and responsible for gene silencing in most eukaryotic cells. Increased evidence has been accumulating over the years about their potential value as biomarkers for several diseases. MicroRNAs were predicted to be involved in nearly all biological processes from development to oncogenesis. In this review, we address the importance of circulating microRNAs in different conditions associated with pregnancy starting with the implantation period to preeclampsia and we shortly describe the correlation between placental circulating miRNAs and pregnancy status. We also discuss the importance of microRNAs in recurrent abortion and ectopic pregnancy. Dragos Cretoiu, Jiahong Xu, Junjie Xiao, Nicolae Suciu, and Sanda Maria Cretoiu Copyright © 2016 Dragos Cretoiu et al. All rights reserved. Discovery and Validation of Hypermethylated Markers for Colorectal Cancer Thu, 14 Jul 2016 08:17:57 +0000 http://www.hindawi.com/journals/dm/2016/2192853/ Colorectal carcinoma (CRC) is one of the most prevalent malignant tumors worldwide. Screening and early diagnosis are critical for the clinical management of this disease. DNA methylation changes have been regarded as promising biomarkers for CRC diagnosis. Here, we map DNA methylation profiling on CRC in six CRCs and paired normal samples using a 450 K bead array. Further analysis confirms the methylation status of candidates in two data sets from the Gene Expression Omnibus. Receiver operating characteristic (ROC) curves are calculated to determine the diagnostic performances. We identify 1549 differentially methylated regions (DMRs) showing differences in methylation between CRC and normal tissue. Two genes (ADD2 and AKR1B1), related to the DMRs, are selected for further validation. ROC curves show that the areas under the curves of ADD2 and AKR1B1 are higher than that of SEPT9, which has been clinically used as a screening biomarker of CRC. Our data suggests that aberrant DNA methylation of ADD2 and AKR1B1 could be potential screening markers of CRC. Jiufeng Wei, Guodong Li, Shuwei Dang, Yuhui Zhou, Kai Zeng, and Ming Liu Copyright © 2016 Jiufeng Wei et al. All rights reserved. A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology Wed, 13 Jul 2016 10:20:43 +0000 http://www.hindawi.com/journals/dm/2016/4895050/ Matrix metalloproteinases are a class of enzymes involved in the degradation of extracellular matrix molecules. While these molecules are exceptionally effective mediators of physiological tissue remodeling, as occurs in wound healing and during embryonic development, pathological upregulation has been implicated in many disease processes. As effectors and indicators of pathological states, matrix metalloproteinases are excellent candidates in the diagnosis and assessment of these diseases. The purpose of this review is to discuss matrix metalloproteinases as they pertain to cartilage health, both under physiological circumstances and in the instances of osteoarthritis and rheumatoid arthritis, and to discuss their utility as biomarkers in instances of the latter. Brandon J. Rose and David L. Kooyman Copyright © 2016 Brandon J. Rose and David L. Kooyman. All rights reserved. Disease Biomarkers in Gastrointestinal Malignancies Sun, 03 Jul 2016 07:24:48 +0000 http://www.hindawi.com/journals/dm/2016/4714910/ Omeed Moaven, Hamid Raziee, Wilbur Bowne, Mohammad Reza Abbaszadegan, and Bryan C. Fuchs Copyright © 2016 Omeed Moaven et al. All rights reserved. Proteomic-Based Approaches for the Study of Cytokines in Lung Cancer Thu, 30 Jun 2016 15:00:12 +0000 http://www.hindawi.com/journals/dm/2016/2138627/ Proteomic techniques are currently used to understand the biology of different human diseases, including studies of the cell signaling pathways implicated in cancer progression, which is important in knowing the roles of different proteins in tumor development. Due to its poor prognosis, proteomic approaches are focused on the identification of new biomarkers for the early diagnosis, prognosis, and targeted treatment of lung cancer. Cytokines are proteins involved in inflammatory processes and have been proposed as lung cancer biomarkers and therapeutic targets because it has been reported that some cytokines play important roles in tumor development, invasion, and metastasis. In this review, we aim to summarize the different proteomic techniques used to discover new lung cancer biomarkers and therapeutic targets. Several cytokines have been identified as important players in lung cancer using these techniques. We underline the most important cytokines that are useful as biomarkers and therapeutic targets. We also summarize some of the therapeutic strategies targeted for these cytokines in lung cancer. Ángela Marrugal, Laura Ojeda, Luis Paz-Ares, Sonia Molina-Pinelo, and Irene Ferrer Copyright © 2016 Ángela Marrugal et al. All rights reserved. Expressions of Matrix Metalloproteinases 2, 7, and 9 in Carcinogenesis of Pancreatic Ductal Adenocarcinoma Sun, 26 Jun 2016 09:01:37 +0000 http://www.hindawi.com/journals/dm/2016/9895721/ Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease, usually diagnosed in an advanced stage which gives a slight chance of recovery. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that participate in tissue remodeling and stimulate neovascularization and inflammatory response. The aim of the study was to evaluate the expression of MMP-2, MMP-7, and MMP-9 in normal ducts, tumor pancreatic adenocarcinoma cells, and peritumoral stroma in correlation with clinicohistopathological parameters. The study material was obtained from 29 patients with pancreatic ductal adenocarcinoma. The expressions of MMP-2, MMP-7, and MMP-9 were performed by immunohistochemical technique. Microvessel density (MVD) was visualized by special immunostaining. The expressions of MMP-2, MMP-7, and MMP-9 were mainly observed in tumor cells and peritumoral stroma. MMP-2 expression in cancer cells was correlated with female gender, stronger inflammation, and histopathological type of cancer (, ; , ; , , resp.). The expression of MMP-7 in tumor cells was found to positively correlate with the presence of necrosis and negatively correlate with MVD (, ; , ). We also showed that positive MMP-9 expression in tumor cells was associated with MVD (, ); however, it was not statistically significant. Our results demonstrate that MMP-2, MMP-7, and MMP-9 expressions correlate with various morphological features of the PDAC tumor such as inflammation, necrosis, and formation of the new blood vessels. Katarzyna Jakubowska, Anna Pryczynicz, Joanna Januszewska, Iwona Sidorkiewicz, Andrzej Kemona, Andrzej Niewiński, Łukasz Lewczuk, Bogusław Kędra, and Katarzyna Guzińska-Ustymowicz Copyright © 2016 Katarzyna Jakubowska et al. All rights reserved. Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers Wed, 15 Jun 2016 13:37:59 +0000 http://www.hindawi.com/journals/dm/2016/1427849/ Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients. Chang-Qing Yin, Chun-Hui Yuan, Zhen Qu, Qing Guan, Hao Chen, and Fu-Bing Wang Copyright © 2016 Chang-Qing Yin et al. All rights reserved.