BioMed Research International http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile Sun, 21 Sep 2014 06:53:27 +0000 http://www.hindawi.com/journals/bmri/2014/683068/ Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. Karina Sánchez-Reyes, Alejandro Bravo-Cuellar, Georgina Hernández-Flores, José Manuel Lerma-Díaz, Luis Felipe Jave-Suárez, Paulina Gómez-Lomelí, Ruth de Celis, Adriana Aguilar-Lemarroy, Jorge Ramiro Domínguez-Rodríguez, and Pablo Cesar Ortiz-Lazareno Copyright © 2014 Karina Sánchez-Reyes et al. All rights reserved. Exercise Improves Immune Function, Antidepressive Response, and Sleep Quality in Patients with Chronic Primary Insomnia Sun, 21 Sep 2014 06:25:01 +0000 http://www.hindawi.com/journals/bmri/2014/498961/ The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm3) and CD8 (532.4 ± 259 to 435.7 ± 204 mm3). Decreases in cortisol were significantly correlated with increases in total sleep time and REM sleep . In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables. Giselle Soares Passos, Dalva Poyares, Marcos Gonçalves Santana, Alexandre Abílio de Souza Teixeira, Fábio Santos Lira, Shawn D. Youngstedt, Ronaldo Vagner Thomatieli dos Santos, Sergio Tufik, and Marco Túlio de Mello Copyright © 2014 Giselle Soares Passos et al. All rights reserved. From Pathways to Targets: Understanding the Mechanisms behind Polyglutamine Disease Sun, 21 Sep 2014 06:05:06 +0000 http://www.hindawi.com/journals/bmri/2014/701758/ The history of polyglutamine diseases dates back approximately 20 years to the discovery of a polyglutamine repeat in the androgen receptor of SBMA followed by the identification of similar expansion mutations in Huntington’s disease, SCA1, DRPLA, and the other spinocerebellar ataxias. This common molecular feature of polyglutamine diseases suggests shared mechanisms in disease pathology and neurodegeneration of disease specific brain regions. In this review, we discuss the main pathogenic pathways including proteolytic processing, nuclear shuttling and aggregation, mitochondrial dysfunction, and clearance of misfolded polyglutamine proteins and point out possible targets for treatment. Jonasz Jeremiasz Weber, Anna Sergeevna Sowa, Tina Binder, and Jeannette Hübener Copyright © 2014 Jonasz Jeremiasz Weber et al. All rights reserved. Erratum to “A Bioinformatics Pipeline for the Analyses of Viral Escape Dynamics and Host Immune Responses during an Infection” Sun, 21 Sep 2014 06:02:49 +0000 http://www.hindawi.com/journals/bmri/2014/680249/ Preston Leung, Rowena Bull, Andrew Lloyd, and Fabio Luciani Copyright © 2014 Preston Leung et al. All rights reserved. Effect of Ovariectomy on Stimulating Intracortical Remodeling in Rats Sun, 21 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/421431/ Objective. Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. Materials and Methods. Sixteen 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT) and histomorphometric assessments. Results. Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3, ) and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, ) in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. Conclusion. For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process. Chun Lei Li, Xi Ling Liu, Wei Xin Cai, Weijia William Lu, Roger A. Zwahlen, and Li Wu Zheng Copyright © 2014 Chun Lei Li et al. All rights reserved. Differential Protein Network Analysis of the Immune Cell Lineage Sun, 21 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/363408/ Recently, the Immunological Genome Project (ImmGen) completed the first phase of the goal to understand the molecular circuitry underlying the immune cell lineage in mice. That milestone resulted in the creation of the most comprehensive collection of gene expression profiles in the immune cell lineage in any model organism of human disease. There is now a requisite to examine this resource using bioinformatics integration with other molecular information, with the aim of gaining deeper insights into the underlying processes that characterize this immune cell lineage. We present here a bioinformatics approach to study differential protein interaction mechanisms across the entire immune cell lineage, achieved using affinity propagation applied to a protein interaction network similarity matrix. We demonstrate that the integration of protein interaction networks with the most comprehensive database of gene expression profiles of the immune cells can be used to generate hypotheses into the underlying mechanisms governing the differentiation and the differential functional activity across the immune cell lineage. This approach may not only serve as a hypothesis engine to derive understanding of differentiation and mechanisms across the immune cell lineage, but also help identify possible immune lineage specific and common lineage mechanism in the cells protein networks. Trevor Clancy and Eivind Hovig Copyright © 2014 Trevor Clancy and Eivind Hovig. All rights reserved. Computational Approaches for Microalgal Biofuel Optimization: A Review Sun, 21 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/649453/ The increased demand and consumption of fossil fuels have raised interest in finding renewable energy sources throughout the globe. Much focus has been placed on optimizing microorganisms and primarily microalgae, to efficiently produce compounds that can substitute for fossil fuels. However, the path to achieving economic feasibility is likely to require strain optimization through using available tools and technologies in the fields of systems and synthetic biology. Such approaches invoke a deep understanding of the metabolic networks of the organisms and their genomic and proteomic profiles. The advent of next generation sequencing and other high throughput methods has led to a major increase in availability of biological data. Integration of such disparate data can help define the emergent metabolic system properties, which is of crucial importance in addressing biofuel production optimization. Herein, we review major computational tools and approaches developed and used in order to potentially identify target genes, pathways, and reactions of particular interest to biofuel production in algae. As the use of these tools and approaches has not been fully implemented in algal biofuel research, the aim of this review is to highlight the potential utility of these resources toward their future implementation in algal research. Joseph Koussa, Amphun Chaiboonchoe, and Kourosh Salehi-Ashtiani Copyright © 2014 Joseph Koussa et al. All rights reserved. Protective Role of 5-Lipoxigenase during Leishmania infantum Infection Is Associated with Th17 Subset Sun, 21 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/264270/ Visceral leishmaniasis (VL) is a chronic and fatal disease caused by Leishmania infantum in Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Leucotriens are lipid mediators synthesized by 5-lipoxygenase (5-LO) and they display a protective role against protozoan parasites by inducing several functions in leucocytes. We determined the role of 5-LO activity in parasite control, focusing on the inflammatory immune response against Leishmania infantum infection. LTB4 is released during in vitro infection. The genetic ablation of 5-LO promoted susceptibility in highly resistant mice strains, harboring more parasites into target organs. The susceptibility was related to the failure of neutrophil migration to the infectious foci. Investigating the neutrophil failure, there was a reduction of proinflammatory cytokines involved in the related Th17 axis released into the organs. Genetic ablation of 5-LO reduced the CD4+T cells producing IL-17, without interfering in Th1 subset. L. infantum failed to activate DC from , showing reduced surface costimulatory molecule expression and proinflammatory cytokines involved in Th17 differentiation. BLT1 blockage with selective antagonist interferes with DC maturation and proinflammatory cytokines release. Thus, 5-LO activation coordinates the inflammatory immune response involved in the control of VL. Laís Amorim Sacramento, Fernando Q. Cunha, Roque Pacheco de Almeida, João Santana da Silva, and Vanessa Carregaro Copyright © 2014 Laís Amorim Sacramento et al. All rights reserved. Tumor Suppression and Promotion by Autophagy Thu, 18 Sep 2014 12:53:15 +0000 http://www.hindawi.com/journals/bmri/2014/603980/ Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer. Yenniffer Ávalos, Jimena Canales, Roberto Bravo-Sagua, Alfredo Criollo, Sergio Lavandero, and Andrew F. G. Quest Copyright © 2014 Yenniffer Ávalos et al. All rights reserved. Gender-Dependent Effect of GSTM1 Genotype on Childhood Asthma Associated with Prenatal Tobacco Smoke Exposure Thu, 18 Sep 2014 12:38:05 +0000 http://www.hindawi.com/journals/bmri/2014/769452/ It remains unclear whether the GSTM1 genotype interacts with tobacco smoke exposure (TSE) in asthma development. This study aimed to investigate the interactions among GSTM1 genotype, gender, and prenatal TSE with regard to childhood asthma development. In a longitudinal birth cohort in Taiwan, 756 newborns completed a 6-year follow-up, and 591 children with DNA samples available for GSTM1 genotyping were included in the study, and the interactive influences of gender-GSTM1 genotyping-prenatal TSE on childhood asthma development were analyzed. Among these 591 children, 138 (23.4%) had physician-diagnosed asthma at 6 years of age, and 347 (58.7%) were null-GSTM1. Prenatal TSE significantly increased the prevalence of childhood asthma in null-GSTM1 children relative to those with positive GSTM1. Further analysis showed that prenatal TSE significantly increased the risk of childhood asthma in girls with null-GSTM1. Furthermore, among the children without prenatal TSE, girls with null-GSTM1 had a significantly lower risk of developing childhood asthma and a lower total IgE level at 6 years of age than those with positive GSTM1. This study demonstrates that the GSTM1 null genotype presents a protective effect against asthma development in girls, but the risk of asthma development increases significantly under prenatal TSE. Chih-Chiang Wu, Chia-Yu Ou, Jen-Chieh Chang, Te-Yao Hsu, Ho-Chang Kuo, Chieh-An Liu, Chih-Lu Wang, Chia-Ju Chuang, Hau Chuang, Hsiu-Mei Liang, and Kuender D. Yang Copyright © 2014 Chih-Chiang Wu et al. All rights reserved. Myristic Acid Produces Anxiolytic-Like Effects in Wistar Rats in the Elevated Plus Maze Thu, 18 Sep 2014 12:23:46 +0000 http://www.hindawi.com/journals/bmri/2014/492141/ A mixture of eight fatty acids (linoleic, palmitic, stearic, myristic, elaidic, lauric, oleic, and palmitoleic acids) at similar concentrations identified in human amniotic fluid produces anxiolytic-like effects comparable to diazepam in Wistar rats. However, individual effects of each fatty acid remain unexplored. In Wistar rats, we evaluated the separate action of each fatty acid at the corresponding concentrations previously found in human amniotic fluid on anxiety-like behaviour. Individual effects were compared with vehicle, an artificial mixture of the same eight fatty acids, and a reference anxiolytic drug (diazepam, 2 mg/kg). Myristic acid, the fatty acid mixture, and diazepam increased the time spent in the open arms of the elevated plus maze and reduced the anxiety index compared with vehicle, without altering general locomotor activity. The other fatty acids had no effect on anxiety-like behaviour, but oleic acid reduced locomotor activity. Additionally, myristic acid produced anxiolytic-like effects only when the concentration corresponded to the one identified in human amniotic fluid (30 𝜇g/mL) but did not alter locomotor activity. We conclude that of the eight fatty acids contained in the fatty acid mixture, only myristic acid produces anxiolytic-like effects when administered individually at a similar concentration detected in human amniotic fluid. Carlos M. Contreras, Juan Francisco Rodríguez-Landa, Rosa Isela García-Ríos, Jonathan Cueto-Escobedo, Gabriel Guillen-Ruiz, and Blandina Bernal-Morales Copyright © 2014 Carlos M. Contreras et al. All rights reserved. Normoxic and Hyperoxic Cardiopulmonary Bypass in Congenital Heart Disease Thu, 18 Sep 2014 09:08:39 +0000 http://www.hindawi.com/journals/bmri/2014/678268/ Cyanotic congenital heart disease comprises a diverse spectrum of anatomical pathologies. Common to all, however, is chronic hypoxia before these lesions are operated upon when cardiopulmonary bypass is initiated. A range of functional and structural adaptations take place in the chronically hypoxic heart, which, whilst protective in the hypoxic state, are deleterious when the availability of oxygen to the myocardium is suddenly improved. Conventional cardiopulmonary bypass delivers hyperoxic perfusion to the myocardium and is associated with cardiac injury and systemic stress, whilst a normoxic perfusate protects against these insults. Amir Mokhtari and Martin Lewis Copyright © 2014 Amir Mokhtari and Martin Lewis. All rights reserved. EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia Thu, 18 Sep 2014 08:31:19 +0000 http://www.hindawi.com/journals/bmri/2014/548097/ Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis. A. Morales-Sánchez, E. N. Pompa-Mera, A. Fajardo-Gutiérrez, F. J. Alvarez-Rodríguez, V. C. Bekker-Méndez, J. de Diego Flores-Chapa, J. Flores-Lujano, E. Jiménez-Hernández, J. G. Peñaloza-González, M. C. Rodríguez-Zepeda, J. R. Torres-Nava, M. M. Velázquez-Aviña, R. Amador-Sánchez, M. Alvarado-Ibarra, N. Reyes-Zepeda, R. M. Espinosa-Elizondo, M. L. Pérez-Saldivar, J. C. Núñez-Enríquez, J. M. Mejía-Aranguré, and E. M. Fuentes-Pananá Copyright © 2014 A. Morales-Sánchez et al. All rights reserved. 18F-Fluorodeoxyglucose Uptake in Abdominal Aortic Aneurysms: A Useful Biomarker of AAA Rupture Risk Thu, 18 Sep 2014 08:17:01 +0000 http://www.hindawi.com/journals/bmri/2014/930738/ Kosmas I. Paraskevas, Dimitri P. Mikhailidis, and Frank J. Veith Copyright © 2014 Kosmas I. Paraskevas et al. All rights reserved. Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations Thu, 18 Sep 2014 08:08:35 +0000 http://www.hindawi.com/journals/bmri/2014/389869/ Carborane-based compounds are promising lead structures for development of inhibitors of carbonic anhydrases (CAs). Here, we report structural and computational analysis applicable to structure-based design of carborane compounds with selectivity toward the cancer-specific CAIX isoenzyme. We determined the crystal structure of CAII in complex with 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane at 1.0 Å resolution and used this structure to model the 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane interactions with CAIX. A virtual glycine scan revealed the contributions of individual residues to the energy of binding of 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane to CAII and CAIX, respectively. Pavel Mader, Adam Pecina, Petr Cígler, Martin Lepšík, Václav Šícha, Pavel Hobza, Bohumír Grüner, Jindřich Fanfrlík, Jiří Brynda, and Pavlína Řezáčová Copyright © 2014 Pavel Mader et al. All rights reserved. Purification and Characterization of Alkaline-Thermostable Protease Enzyme from Pitaya (Hylocereus polyrhizus) Waste: A Potential Low Cost of the Enzyme Thu, 18 Sep 2014 07:41:10 +0000 http://www.hindawi.com/journals/bmri/2014/259238/ The thermoalkaline protease enzyme from pitaya (Hylocereus polyrhizus) waste was purified by a factor of 221.2 with 71.3% recovery using ammonium sulphate precipitation, gel filtration, and cation exchange chromatography. Gel filtration chromatography together with sodium dodecyl sulphate gel electrophoresis (SDS-PAGE) revealed that the enzyme is monomeric with a molecular weight of 26.7 kDa. The apparent and of the protease were 2.8 mg/mL and 31.20 u/min, respectively. The optimum pH and temperature were 8.0 and 70°C. The enzyme was highly active and stable over a wide pH range (from pH 3.0 to pH 11.0 with the optimum activity at pH 8.0). The protease has broad specificity toward azocasein, casein, hemoglobin, and gelatine. Activity of the enzyme was inhibited by Fe2+ and Zn2+, while protease activity was increased in the presence of Ca2+ and Mg2+ and Cu2+ by factors of 125%, 110%, and 105%, respectively. The alkaline protease showed extreme stability toward surfactants and oxidizing agent. The purified protease exhibited extreme stability in the presence of organic solvents and inhibitors. In addition, the enzyme was relativity stable toward organic solvents and chelating agents, such as ethylenediaminetetraacetic acid (EDTA). The enzyme, derived from pitaya peel, possesses unique characteristics and could be used in various industrial and biotechnological applications. Mehrnoush Amid, Mohd Yazid ABD Manap, and Nor Khanani Zohdi Copyright © 2014 Mehrnoush Amid et al. All rights reserved. Evolution of Network Biomarkers from Early to Late Stage Bladder Cancer Samples Thu, 18 Sep 2014 06:53:32 +0000 http://www.hindawi.com/journals/bmri/2014/159078/ We use a systems biology approach to construct protein-protein interaction networks (PPINs) for early and late stage bladder cancer. By comparing the networks of these two stages, we find that both networks showed very significantly different mechanisms. To obtain the differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two bladder cancer stages using microarray data from cancer cells and their adjacent noncancer cells, respectively. With their carcinogenesis relevance values (CRVs), we identified 152 and 50 significant proteins and their PPI networks (network markers) for early and late stage bladder cancer by statistical assessment. To investigate the evolution of network biomarkers in the carcinogenesis process, primary pathway analysis showed that the significant pathways of early stage bladder cancer are related to ordinary cancer mechanisms, while the ribosome pathway and spliceosome pathway are most important for late stage bladder cancer. Their only intersection is the ubiquitin mediated proteolysis pathway in the whole stage of bladder cancer. The evolution of network biomarkers from early to late stage can reveal the carcinogenesis of bladder cancer. The findings in this study are new clues specific to this study and give us a direction for targeted cancer therapy, and it should be validated in vivo or in vitro in the future. Yung-Hao Wong, Cheng-Wei Li, and Bor-Sen Chen Copyright © 2014 Yung-Hao Wong et al. All rights reserved. 18FDG, [18F]FLT, [18F]FAZA, and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts Thu, 18 Sep 2014 05:25:40 +0000 http://www.hindawi.com/journals/bmri/2014/787365/ Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG), 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET. György Trencsényi, Teréz Márián, Imre Lajtos, Zoltán Krasznai, László Balkay, Miklós Emri, Pál Mikecz, Katalin Goda, Gábor Szalóki, István Juhász, Enikő Németh, Tünde Miklovicz, Gábor Szabó, and Zoárd T. Krasznai Copyright © 2014 György Trencsényi et al. All rights reserved. Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair Thu, 18 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/845323/ Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration. Justin R. Siebert, Amanda Conta Steencken, and Donna J. Osterhout Copyright © 2014 Justin R. Siebert et al. All rights reserved. Serial Changes of Neointimal Tissue after Everolimus-Eluting Stent Implantation in Porcine Coronary Artery: An Optical Coherence Tomography Analysis Thu, 18 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/851676/ Purposes. The serial changes in neointimal tissues were compared between everolimus-eluting stent (EES) and bare-metal stent (BMS) in the porcine coronary artery using optical coherence tomography (OCT). Methods. Serial (1, 3, and 6 month follow-up after stent implantation) OCT examinations were performed in 15 swine with 15 BMS- and 15 EES-treated lesions in porcine coronary arteries. Results. In BMS-implanted lesions, neointimal volume decreased from 7.3 mm3 to 6.9 mm3 and 6.4 mm3 at 1, 3, and 6 months follow-up without statistical significance (). At the time points of 1, 3, and 6 months, neointimal tissue appearance was mainly a homogeneous pattern (80.0%, 93.3%, and 100%, resp.), while the other pattern was layered. In contrast, in EES-implanted lesions, neointimal volume significantly increased from 4.8 mm3 to 9.8 mm3 between 1 and 3 months but significantly decreased to 8.6 mm3 between 3 and 6 months (). Between 1 and 3 months, the layered pattern of neointimal tissue increased from 26.7% to 66.7% but decreased to 20.0% between 3 and 6 months. Conclusions. EES had a biphasic pattern of neointimal amounts that correlated with changes in neointimal morphology. Hoyoun Won, Jung-Sun Kim, Dong-Ho Shin, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, and Myeong-Ki Hong Copyright © 2014 Hoyoun Won et al. All rights reserved. Comparative Diagnostic Accuracy of Ganglion Cell-Inner Plexiform and Retinal Nerve Fiber Layer Thickness Measures by Cirrus and Spectralis Optical Coherence Tomography in Relapsing-Remitting Multiple Sclerosis Thu, 18 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/128517/ Objective. To estimate sensitivity and specificity of several optical coherence tomography (OCT) measurements for detecting retinal thickness changes in patients with relapsing-remitting multiple sclerosis (RRMS), such as macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with Cirrus (OCT) and peripapillary retinal nerve fiber layer (pRNFL) thickness measured with Cirrus and Spectralis OCT. Methods. Seventy patients (140 eyes) with RRMS and seventy matched healthy subjects underwent pRNFL and GCIPL thickness analysis using Cirrus OCT and pRNFL using Spectralis OCT. A prospective, cross-sectional evaluation of sensitivities and specificities was performed using latent class analysis due to the absence of a gold standard. Results. GCIPL measures had higher sensitivity and specificity than temporal pRNFL measures obtained with both OCT devices. Average GCIPL thickness was significantly more sensitive than temporal pRNFL by Cirrus (96.34% versus 58.41%) and minimum GCIPL thickness was significantly more sensitive than temporal pRNFL by Spectralis (96.41% versus 69.69%). Generalised estimating equation analysis revealed that age (), optic neuritis antecedent (), and disease duration () were significantly associated with abnormal results in average GCIPL thickness. Conclusion. Average and minimum GCIPL measurements had significantly better sensitivity to detect retinal thickness changes in RRMS than temporal pRNFL thickness measured by Cirrus and Spectralis OCT, respectively. Julio J. González-López, Gema Rebolleda, Marina Leal, Noelia Oblanca, Francisco J. Muñoz-Negrete, Lucienne Costa-Frossard, and José C. Álvarez-Cermeño Copyright © 2014 Julio J. González-López et al. All rights reserved. Lenalidomide Induces Immunomodulation in Chronic Lymphocytic Leukemia and Enhances Antitumor Immune Responses Mediated by NK and CD4 T Cells Wed, 17 Sep 2014 11:59:19 +0000 http://www.hindawi.com/journals/bmri/2014/265840/ Lenalidomide is an immunomodulatory drug with therapeutic activity in chronic lymphocytic leukemia (CLL). However, it has pleiotropic effects, and the mechanism of action responsible for its therapeutic activity has not been well defined yet. Herein, we show that lenalidomide treatment does not have an effect on the proliferation of leukemia cells, but it increases the proliferation of B cells from healthy donors. Lenalidomide did not exert a direct effect on the apoptosis of leukemia cells obtained from CLL patients, although it indirectly induced their apoptosis through the activation of nonmalignant immune cells. Thus, lenalidomide markedly increased the proliferation of NK and CD4 T cells. The effect of lenalidomide on NK cells was secondary to the induction of IL-2 production by CD4 T cells. Accordingly, depletion of T cells or blockade of IL-2 activity completely abrogated the proliferation of NK cells. Additionally, lenalidomide enhanced NK and NKT-like cell-mediated natural cytotoxicity against leukemia cells from CLL patients. Lenalidomide also upregulated CD20 expression on leukemia cells and, accordingly, it had a synergistic effect with rituximab on promoting antibody-dependent cell-mediated cytotoxicity against primary leukemia cells. Overall, these observations provide a support for combining lenalidomide with rituximab as a treatment in CLL. Andrea Acebes-Huerta, Leticia Huergo-Zapico, Ana Pilar Gonzalez-Rodriguez, Azahara Fernandez-Guizan, Angel R. Payer, Alejandro López-Soto, and Segundo Gonzalez Copyright © 2014 Andrea Acebes-Huerta et al. All rights reserved. Pentachlorophenol Degradation by Janibacter sp., a New Actinobacterium Isolated from Saline Sediment of Arid Land Wed, 17 Sep 2014 11:48:30 +0000 http://www.hindawi.com/journals/bmri/2014/296472/ Many pentachlorophenol- (PCP-) contaminated environments are characterized by low or elevated temperatures, acidic or alkaline pH, and high salt concentrations. PCP-degrading microorganisms, adapted to grow and prosper in these environments, play an important role in the biological treatment of polluted extreme habitats. A PCP-degrading bacterium was isolated and characterized from arid and saline soil in southern Tunisia and was enriched in mineral salts medium supplemented with PCP as source of carbon and energy. Based on 16S rRNA coding gene sequence analysis, the strain FAS23 was identified as Janibacter sp. As revealed by high performance liquid chromatography (HPLC) analysis, FAS23 strain was found to be efficient for PCP removal in the presence of 1% of glucose. The conditions of growth and PCP removal by FAS23 strain were found to be optimal in neutral pH and at a temperature of 30°C. Moreover, this strain was found to be halotolerant at a range of 1–10% of NaCl and able to degrade PCP at a concentration up to 300 mg/L, while the addition of nonionic surfactant (Tween 80) enhanced the PCP removal capacity. Amel Khessairi, Imene Fhoula, Atef Jaouani, Yousra Turki, Ameur Cherif, Abdellatif Boudabous, Abdennaceur Hassen, and Hadda Ouzari Copyright © 2014 Amel Khessairi et al. All rights reserved. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines Wed, 17 Sep 2014 09:19:39 +0000 http://www.hindawi.com/journals/bmri/2014/568693/ Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models. Falko Lange, Benjamin Franz, Claudia Maletzki, Michael Linnebacher, Maja Hühns, and Robert Jaster Copyright © 2014 Falko Lange et al. All rights reserved. Emerging Rapid Resistance Testing Methods for Clinical Microbiology Laboratories and Their Potential Impact on Patient Management Wed, 17 Sep 2014 08:57:44 +0000 http://www.hindawi.com/journals/bmri/2014/375681/ Atypical and multidrug resistance, especially ESBL and carbapenemase expressing Enterobacteriaceae, is globally spreading. Therefore, it becomes increasingly difficult to achieve therapeutic success by calculated antibiotic therapy. Consequently, rapid antibiotic resistance testing is essential. Various molecular and mass spectrometry-based approaches have been introduced in diagnostic microbiology to speed up the providing of reliable resistance data. PCR- and sequencing-based approaches are the most expensive but the most frequently applied modes of testing, suitable for the detection of resistance genes even from primary material. Next generation sequencing, based either on assessment of allelic single nucleotide polymorphisms or on the detection of nonubiquitous resistance mechanisms might allow for sequence-based bacterial resistance testing comparable to viral resistance testing on the long term. Fluorescence in situ hybridization (FISH), based on specific binding of fluorescence-labeled oligonucleotide probes, provides a less expensive molecular bridging technique. It is particularly useful for detection of resistance mechanisms based on mutations in ribosomal RNA. Approaches based on MALDI-TOF-MS, alone or in combination with molecular techniques, like PCR/electrospray ionization MS or minisequencing provide the fastest resistance results from pure colonies or even primary samples with a growing number of protocols. This review details the various approaches of rapid resistance testing, their pros and cons, and their potential use for the diagnostic laboratory. Hagen Frickmann, Wycliffe Omurwa Masanta, and Andreas E. Zautner Copyright © 2014 Hagen Frickmann et al. All rights reserved. Proinflammatory Cytokines Correlate with Depression and Anxiety in Colorectal Cancer Patients Wed, 17 Sep 2014 07:15:35 +0000 http://www.hindawi.com/journals/bmri/2014/739650/ The objective of this study was to investigate whether serum cytokine levels correlate with depression and anxiety in colorectal cancer (CRC) patients. Twenty patients hospitalized for surgical resection of CRC were included in the study group and twenty healthy volunteers comprised the control group. Depression and anxiety were analyzed using the Hospital Anxiety and Depression Scale (HADS), and serum levels of IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, and TGF-β were measured by Cytometric Bead Array. We found that more than half of CRC patients presented clinically significant levels of anxiety or depression, and 65% of them manifested a combination of severe anxiety and depression. CRC patients had increased serum levels of IL-1β, IL-6, IL-8, and TNF-α but lower IL-10 concentrations. Correlation analysis between HADS score and cytokine levels revealed a positive association of anxiety and/or depression with IL-1β, IL-6, IL-8, and TNF-α and a negative correlation with IL-10. These results indicate that circulating proinflammatory cytokines are involved in the pathophysiology of anxiety and depression in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of therapeutic interventions that lead to an improved quality of life and overall survival of CRC patients. Diego Oliveira Miranda, Taís Aparecida Soares de Lima, Lucas Ribeiro Azevedo, Omar Feres, José Joaquim Ribeiro da Rocha, and Gabriela Pereira-da-Silva Copyright © 2014 Diego Oliveira Miranda et al. All rights reserved. Planarians Sense Simulated Microgravity and Hypergravity Wed, 17 Sep 2014 06:44:19 +0000 http://www.hindawi.com/journals/bmri/2014/679672/ Planarians are flatworms, which belong to the phylum Platyhelminthes. They have been a classical subject of study due to their amazing regenerative ability, which relies on the existence of adult totipotent stem cells. Nowadays they are an emerging model system in the field of developmental, regenerative, and stem cell biology. In this study we analyze the effect of a simulated microgravity and a hypergravity environment during the process of planarian regeneration and embryogenesis. We demonstrate that simulated microgravity by means of the random positioning machine (RPM) set at a speed of 60 °/s but not at 10 °/s produces the dead of planarians. Under hypergravity of 3 g and 4 g in a large diameter centrifuge (LDC) planarians can regenerate missing tissues, although a decrease in the proliferation rate is observed. Under 8 g hypergravity small planarian fragments are not able to regenerate. Moreover, we found an effect of gravity alterations in the rate of planarian scission, which is its asexual mode of reproduction. No apparent effects of altered gravity were found during the embryonic development. Teresa Adell, Emili Saló, Jack J. W. A. van Loon, and Gennaro Auletta Copyright © 2014 Teresa Adell et al. All rights reserved. Dendritic Cell Profile Induced by Schistosoma mansoni Antigen in Cutaneous Leishmaniasis Patients Wed, 17 Sep 2014 06:41:25 +0000 http://www.hindawi.com/journals/bmri/2014/743069/ The inflammatory response in cutaneous leishmaniasis (CL), although responsible for controlling the infection, is associated with the pathogenesis of disease. Conversely, the immune response induced by S. mansoni antigens is able to prevent immune-mediated diseases. The aim of this study was to evaluate the potential of the S. mansoni Sm29 antigen to change the profile of monocyte-derived dendritic cells (MoDCs) from subjects with cutaneous leishmaniasis (CL) in vitro. Monocytes derived from the peripheral blood mononuclear cells of twelve patients were cultured with GM-CSF and IL-4 for differentiation into dendritic cells and then stimulated with soluble Leishmania antigen (SLA) in the presence or absence of Sm29 antigen. The expression of surface molecules associated with maturation and activation (HLA-DR, CD40, CD83, CD80, and CD86), inflammation (IL-12, TNF), and downregulation (IL-10, IL-10R) was evaluated using flow cytometry. We observed that the frequencies of HLA-DR, CD83, CD80, and CD86 as well as of IL-10 and IL-10R on MoDCs were higher in cultures stimulated with Sm29, compared to the unstimulated cell cultures. Our results indicate that the Sm29 antigen is able to activate regulatory MoDCs in patients with cutaneous leishmaniasis. It might be useful to control the inflammatory process associated with this disease. Diego Mota Lopes, Jamille Souza Fernandes, Thiago Marconi de Souza Cardoso, Aline Michele Barbosa Bafica, Sérgio Costa Oliveira, Edgar M. Carvalho, Maria Ilma Araujo, and Luciana Santos Cardoso Copyright © 2014 Diego Mota Lopes et al. All rights reserved. Collagen-Glycosaminoglycan Matrix Implantation Promotes Angiogenesis following Surgical Brain Trauma Wed, 17 Sep 2014 06:02:11 +0000 http://www.hindawi.com/journals/bmri/2014/672409/ Surgical brain injury (SBI) is unavoidable during many neurosurgical procedures intrinsically linked to postoperative neurological deficits. We have previously demonstrated that implantation of collagen glycosaminoglycan (CG) following surgical brain injury could significantly promote functional recovery and neurogenesis. In this study we further hypothesized that this scaffold may provide a microenvironment by promoting angiogenesis to favor neurogenesis and subsequent functional recovery. Using the rodent model of surgical brain injury as we previously established, we divided Sprague-Dawley male rats (weighting 300–350 g) into three groups: (1) sham (2) surgical injury with a lesion (L), and (3) L with CG matrix implantation (L + CG). Our results demonstrated that L + CG group showed a statistically significant increase in the density of vascular endothelial cells and blood vessels over time. In addition, tissue concentrations of angiogenic growth factors (such as VEGF, FGF2, and PDGF) significantly increased in L + CG group. These results suggest that implantation of a CG scaffold can promote vascularization accompanied by neurogenesis. This opens prospects for use of CG scaffolds in conditions such as brain injury including trauma and ischemia. Kuo-Feng Huang, Wei-Cherng Hsu, Jong-Kai Hsiao, Gunng-Shinng Chen, and Jia-Yi Wang Copyright © 2014 Kuo-Feng Huang et al. All rights reserved. The Importance of Autophagy Regulation in Breast Cancer Development and Treatment Wed, 17 Sep 2014 05:11:20 +0000 http://www.hindawi.com/journals/bmri/2014/710345/ Breast cancer (BC) is a potentially life-threatening malignant tumor that still causes high mortality among women. One of the mechanisms through which cancer development could be controlled is autophagy. This process exerts different effects during the stages of cancer initiation and progression due to the occurring superimposition of signaling pathways of autophagy and carcinogenesis. Chronic inhibition of autophagy or autophagy deficiency promotes cancer, due to instability of the genome and defective cell growth and as a result of cell stress. However, increased induction of autophagy can become a mechanism which allows tumor cells to survive the conditions of hypoxia, acidosis, or chemotherapy. Therefore, in the development of cancer, autophagy is regarded as a double-edged sword. Determination of the molecular mechanisms underlying autophagy regulation and its role in tumorigenesis is an essential component of modern anticancer strategies. Results of scientific studies show that inhibition of autophagy may enhance the effectiveness of currently used anticancer drugs and other therapies (like radiotherapy). However, in some cases, the promotion of autophagy can induce death and, hence, elimination of the cancer cells and reduction of tumor size. This review summarizes the current knowledge on autophagy regulation in BC and up-to-date anticancer strategies correlated with autophagy. Joanna Magdalena Zarzynska Copyright © 2014 Joanna Magdalena Zarzynska. All rights reserved.