BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Accumulation of Extracellular Hyaluronan by Hyaluronan Synthase 3 Promotes Tumor Growth and Modulates the Pancreatic Cancer Microenvironment Thu, 24 Jul 2014 18:42:37 +0000 Extensive accumulation of the glycosaminoglycan hyaluronan is found in pancreatic cancer. The role of hyaluronan synthases 2 and 3 (HAS2, 3) was investigated in pancreatic cancer growth and the tumor microenvironment. Overexpression of HAS3 increased hyaluronan synthesis in BxPC-3 pancreatic cancer cells. In vivo, overexpression of HAS3 led to faster growing xenograft tumors with abundant extracellular hyaluronan accumulation. Treatment with pegylated human recombinant hyaluronidase (PEGPH20) removed extracellular hyaluronan and dramatically decreased the growth rate of BxPC-3 HAS3 tumors compared to parental tumors. PEGPH20 had a weaker effect on HAS2-overexpressing tumors which grew more slowly and contained both extracellular and intracellular hyaluronan. Accumulation of hyaluronan was associated with loss of plasma membrane E-cadherin and accumulation of cytoplasmic β-catenin, suggesting disruption of adherens junctions. PEGPH20 decreased the amount of nuclear hypoxia-related proteins and induced translocation of E-cadherin and β-catenin to the plasma membrane. Translocation of E-cadherin was also seen in tumors from a transgenic mouse model of pancreatic cancer and in a human non-small cell lung cancer sample from a patient treated with PEGPH20. In conclusion, hyaluronan accumulation by HAS3 favors pancreatic cancer growth, at least in part by decreasing epithelial cell adhesion, and PEGPH20 inhibits these changes and suppresses tumor growth. Anne Kultti, Chunmei Zhao, Netai C. Singha, Susan Zimmerman, Ryan J. Osgood, Rebecca Symons, Ping Jiang, Xiaoming Li, Curtis B. Thompson, Jeffrey R. Infante, Michael A. Jacobetz, David A. Tuveson, Gregory I. Frost, H. Michael Shepard, and Zhongdong Huang Copyright © 2014 Anne Kultti et al. All rights reserved. Detecting Epistatic Interactions in Metagenome-Wide Association Studies by metaBOOST Thu, 24 Jul 2014 18:41:12 +0000 Material and Methods. We recall the definition of epistasis and extend it for metagenomic biomarkers and then we describe the overview of our method metaBOOST and provide detailed information about each step of metaBOOST. Results. We describe the data sources for both simulation studies and real metagenomic datasets. Then, we describe the procedure of simulation studies and provide results for it. After that, we conduct real datasets studies and report the results. Conclusions and Discussion. Finally, we conclude our method and discuss some possible improvements for the future. Mengmeng Wu and Rui Jiang Copyright © 2014 Mengmeng Wu and Rui Jiang. All rights reserved. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury Thu, 24 Jul 2014 12:30:41 +0000 Matrix metalloproteinases (MMPs) significantly contribute to ischemia reperfusion (I/R) injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s) involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2) in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological) conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury. Han-Bin Lin, Virgilio J. J. Cadete, Bikramjit Sra, Jolanta Sawicka, Zhicheng Chen, Lane K. Bekar, Francisco Cayabyab, and Grzegorz Sawicki Copyright © 2014 Han-Bin Lin et al. All rights reserved. Characterization of Morphology and Composition of Inorganic Fillers in Dental Alginates Thu, 24 Jul 2014 11:38:31 +0000 Energy dispersive X-ray spectroscopy microanalysis (EDX), scanning electron microscopy (SEM), and Archimedes’ Principle were used to determine the characteristics of inorganic filler particles in five dental alginates, including Cavex ColorChange (C), Hydrogum 5 (H5), Hydrogum (H), Orthoprint (O), and Jeltrate Plus (JP). The different alginate powders (0.5 mg) were fixed on plastic stubs and sputter coated with carbon for EDX analysis, then coated with gold, and observed using SEM. Volume fractions were determined by weighing a sample of each material in water before and after calcining at 450°C for 3 h. The alginate materials were mainly composed of silicon (Si) by weight (C—81.59%, H—79.89%, O—78.87%, H5—77.95%, JP—66.88%, wt). The filler fractions in volume (vt) were as follows: H5—84.85%, JP—74.76%, H—70.03%, O—68.31%, and C—56.10%. The tested materials demonstrated important differences in the inorganic elemental composition, filler fraction, and particle morphology. Ricardo Danil Guiraldo, Sandrine Bittencourt Berger, Rafael Leonardo Xediek Consani, Simonides Consani, Rodrigo Varella de Carvalho, Murilo Baena Lopes, Luciana Lira Meneghel, Fabiane Borges da Silva, and Mário Alexandre Coelho Sinhoreti Copyright © 2014 Ricardo Danil Guiraldo et al. All rights reserved. Childhood Renal Tumor: A Report from a Chinese Children’s Cancer Group Thu, 24 Jul 2014 11:29:11 +0000 Here we investigated the establishment of multicenter cooperative treatment groups in China, as well as radiotherapy compliance and effectiveness among children with renal tumors. Medical records were reviewed for 316 children with renal tumors diagnosed by a multicenter cooperative group from 14 hospitals in China from 1998 to 2012. Median patient age was 29.5 months (range, 2–173 months old), and male-to-female ratio was 1.4 : 1. After a median follow-up of 22 months (range, 1–177 months), five-year event-free survival rates were 72% overall; 76.1% for favorable histology (251 cases); 59% for unfavorable histology (27 cases); and 91%, 75%, 71%, 53%, and 48.5%, respectively for Stages I, II, III, IV, and V. Following standardized criteria, radiation therapy was indicated for 153 patients, among whom five-year event-free survival was 72.8% for the 95 who received radiation and 24% for the 58 patients who did not. Our results are reasonable but can be further improved and show the feasibility of a multicenter cooperative group model for childhood renal tumor treatment in China. Radiation therapy is important for stage III and IV patients but remains difficult to implement in some parts of China. Government management departments and medical professionals must pay attention to this situation. This clinical trial is registered with ChiCTR-PRCH-14004372. Jiaoyang Cai, Ci Pan, Qin Lu, Jie Yan, Xiuli Ju, Futian Ma, Yiping Zhu, Qiuling Liu, Lirong Sun, Lian Jiang, Lizhi Cao, Fu Li, Zhigang Liu, Lijing Qiao, Dongsheng Huang, Xin Tian, and Jingyan Tang Copyright © 2014 Jiaoyang Cai et al. All rights reserved. Peptide-Ligand Binding Modeling of siRNA with Cell-Penetrating Peptides Thu, 24 Jul 2014 11:26:49 +0000 The binding affinity of a series of cell-penetrating peptides (CPP) was modeled through docking and making use of the number of intermolecular hydrogen bonds, lipophilic contacts, and the number of sp3 molecular orbital hybridization carbons. The new ranking of the peptides is consistent with the experimentally determined efficiency in the downregulation of luciferase activity, which includes the peptides’ ability to bind and deliver the siRNA into the cell. The predicted structures of the complexes of peptides to siRNA were stable throughout 10 ns long, explicit water molecular dynamics simulations. The stability and binding affinity of peptide-siRNA complexes was related to the sidechains and modifications of the CPPs, with the stearyl and quinoline groups improving affinity and stability. The reranking of the peptides docked to siRNA, together with explicit water molecular dynamics simulations, appears to be well suited to describe and predict the interaction of CPPs with siRNA. Alfonso T. García-Sosa, Indrek Tulp, Kent Langel, and Ülo Langel Copyright © 2014 Alfonso T. García-Sosa et al. All rights reserved. Biomedical Data Integration, Modeling, and Simulation in the Era of Big Data and Translational Medicine Thu, 24 Jul 2014 11:01:30 +0000 Bairong Shen, Andrew E. Teschendorff, Degui Zhi, and Junfeng Xia Copyright © 2014 Bairong Shen et al. All rights reserved. Recent Trends in Pharmaceutical Radiochemistry for Molecular PET Imaging Thu, 24 Jul 2014 10:27:22 +0000 Olaf Prante, Roland Haubner, Patrick Riss, and Bernd Neumaier Copyright © 2014 Olaf Prante et al. All rights reserved. Mechanical Models of the Dynamics of Vitreous Substitutes Thu, 24 Jul 2014 10:05:40 +0000 We discuss some aspects of the fluid dynamics of vitreous substitutes in the vitreous chamber, focussing on the flow induced by rotations of the eye bulb. We use simple, yet not trivial, theoretical models to highlight mechanical concepts that are relevant to understand the dynamics of vitreous substitutes and also to identify ideal properties for vitreous replacement fluids. We first recall results by previous authors, showing that the maximum shear stress on the retina grows with increasing viscosity of the fluid up to a saturation value. We then investigate how the wall shear stress changes if a thin layer of aqueous humour is present in the vitreous chamber, separating the retina from the vitreous replacement fluid. The theoretical predictions show that the existence of a thin layer of aqueous is sufficient to substantially decrease the shear stress on the retina. We finally discuss a theoretical model that predicts the stability conditions of the interface between the aqueous and a vitreous substitute. We discuss the implications of this model to understand the mechanisms leading to the formation of emulsion in the vitreous chamber, showing that instability of the interface is possible in a range of parameters relevant for the human eye. Krystyna Isakova, Jan O. Pralits, Rodolfo Repetto, and Mario R. Romano Copyright © 2014 Krystyna Isakova et al. All rights reserved. miRNA Transcriptome of Hypertrophic Skeletal Muscle with Overexpressed Myostatin Propeptide Thu, 24 Jul 2014 10:02:43 +0000 MicroRNAs (miRNAs) play an imperative role in cell proliferation, differentiation, and cell metabolism through regulation of gene expression. Skeletal muscle hypertrophy that results from myostatin depression by its propeptide provides an interesting model to understand how miRNA transcriptome is involved in myostatin-based fiber hypertrophy. This study employed Solexa deep sequencing followed by Q-PCR methods to analyze miRNA transcriptome of skeletal muscle of myostatin propeptide transgenic mice in comparison with their littermate controls. A total of 461 mature known and 69 novel miRNAs were reported from this study. Fifty-seven miRNAs were expressed differentially between transgenic and littermate controls, of which most abundant miRNAs, miR-133a and 378a, were significantly differentially expressed. Expression profiling was validated on 8 known and 2 novel miRNAs. The miRNA targets prediction and pathway analysis showed that FST, SMAD3, TGFBR1, and AcvR1a genes play a vital role in skeletal muscle hypertrophy in the myostatin propeptide transgenic mice. It is predicted that miR-101 targeted to TGFBR1 and SMAD3, miR-425 to TGFBR2 and FST, and miR-199a to AcvR2a and TGF-β genes. In conclusion, the study offers initial miRNA profiling and methodology of miRNA targets prediction for myostatin-based hypertrophy. These differentially expressed miRNAs are proposed as candidate miRNAs for skeletal muscle hypertrophy. Ruheena Javed, Lu Jing, Jinzeng Yang, Xinyun Li, Jianhua Cao, and Shuhong Zhao Copyright © 2014 Ruheena Javed et al. All rights reserved. N-Acyl Homoserine Lactone-Mediated Quorum Sensing with Special Reference to Use of Quorum Quenching Bacteria in Membrane Biofouling Control Thu, 24 Jul 2014 09:59:53 +0000 Membrane biofouling remains a severe problem to be addressed in wastewater treatment systems affecting reactor performance and economy. The finding that many wastewater bacteria rely on N-acyl homoserine lactone-mediated quorum sensing to synchronize their activities essential for biofilm formations; the quenching bacterial quorum sensing suggests a promising approach for control of membrane biofouling. A variety of quorum quenching compounds of both synthetic and natural origin have been identified and found effective in inhibition of membrane biofouling with much less environmental impact than traditional antimicrobials. Work over the past few years has demonstrated that enzymatic quorum quenching mechanisms are widely conserved in several prokaryotic organisms and can be utilized as a potent tool for inhibition of membrane biofouling. Such naturally occurring bacterial quorum quenching mechanisms also play important roles in microbe-microbe interactions and have been used to develop sustainable nonantibiotic antifouling strategies. Advances in membrane fabrication and bacteria entrapment techniques have allowed the implication of such quorum quenching bacteria for better design of membrane bioreactor with improved antibiofouling efficacies. In view of this, the present paper is designed to review and discuss the recent developments in control of membrane biofouling with special emphasis on quorum quenching bacteria that are applied in membrane bioreactors. Harshad Lade, Diby Paul, and Ji Hyang Kweon Copyright © 2014 Harshad Lade et al. All rights reserved. 1,3,4-Oxadiazole Derivatives: Synthesis, Characterization, Antimicrobial Potential, and Computational Studies Thu, 24 Jul 2014 09:52:50 +0000 We report the synthesis and biological assessment of 1,3,4-oxadiazole substituted 24 derivatives as novel, potential antibacterial agents. The structures of the newly synthesized derivatives were established by the combined practice of UV, IR, 1H NMR, 13C NMR, and mass spectrometry. Further these synthesized derivatives were subjected to antibacterial activity against all the selected microbial strains in comparison with amoxicillin and cefixime. The antibacterial activity of synthesized derivatives was correlated with their physicochemical and structural properties by QSAR analysis using computer assisted multiple regression analysis and four sound predictive models were generated with good , , and Fischer statistic. The derivatives with potent antibacterial activity were subjected to molecular docking studies to investigate the interactions between the active derivatives and amino acid residues existing in the active site of peptide deformylase to assess their antibacterial potential as peptide deformylase inhibitor. Suman Bala, Sunil Kamboj, Anu Kajal, Vipin Saini, and Deo Nanadan Prasad Copyright © 2014 Suman Bala et al. All rights reserved. Innervation of a Prefabricated Flap: A New Experimental Model Thu, 24 Jul 2014 09:27:39 +0000 Introduction. Flap innervation by neoaxonogenesis is a promising field of investigation. The authors evaluated the possibility of innervating an acellular collagen scaffold as component of a potential prefabricated flap. Materials and Methods. Collagen matrix sheets were implanted around the femoral bundle of a murine model to produce two flaps on proximal and distal nerve stumps based on a flow-through model. After thirty days, nerve regeneration and integration into the collagen matrix were evaluated. The specimens were microscopically analyzed to study Schwann cell colonization and axonal integration with the matrix. Axonal count and density were assessed and statistically evaluated. Results. Qualitative structural and ultrastructural evaluation indicated integration, with axonal fibers merged within the collagen matrix, along with a newly formed vascular network on the proximal flap. Wallerian degeneration occurred inside the distal chamber. Axonal count and density did not show statistically significant differences between the nerve inside the proximal flap and the control side. Conclusions. Innervation of an acellular matrix can be obtained by direct nerve stump implantation. The flow-through system was relatively easy to build and reliable to provide adequate blood supply. The collagen scaffold may be a promising support or further studies of preinnervated microsurgical flaps. Marco Romeo, Giuseppe Cuccia, Shan Shan Qiu, Stefania Raimondo, Stefano Geuna, and Bernardo Hontanilla Copyright © 2014 Marco Romeo et al. All rights reserved. Sequence Alignment Tools: One Parallel Pattern to Rule Them All? Thu, 24 Jul 2014 09:22:56 +0000 In this paper, we advocate high-level programming methodology for next generation sequencers (NGS) alignment tools for both productivity and absolute performance. We analyse the problem of parallel alignment and review the parallelisation strategies of the most popular alignment tools, which can all be abstracted to a single parallel paradigm. We compare these tools to their porting onto the FastFlow pattern-based programming framework, which provides programmers with high-level parallel patterns. By using a high-level approach, programmers are liberated from all complex aspects of parallel programming, such as synchronisation protocols, and task scheduling, gaining more possibility for seamless performance tuning. In this work, we show some use cases in which, by using a high-level approach for parallelising NGS tools, it is possible to obtain comparable or even better absolute performance for all used datasets. Claudia Misale, Giulio Ferrero, Massimo Torquati, and Marco Aldinucci Copyright © 2014 Claudia Misale et al. All rights reserved. The N-Terminal Domain of Human DNA Helicase Rtel1 Contains a Redox Active Iron-Sulfur Cluster Thu, 24 Jul 2014 09:20:31 +0000 Human telomere length regulator Rtel1 is a superfamily II DNA helicase and is essential for maintaining proper length of telomeres in chromosomes. Here we report that the N-terminal domain of human Rtel1 (RtelN) expressed in Escherichia coli cells produces a protein that contains a redox active iron-sulfur cluster with the redox midpoint potential of −248 ± 10 mV (pH 8.0). The iron-sulfur cluster in RtelN is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster. Purified RtelN retains a weak binding affinity for the single-stranded (ss) and double-stranded (ds) DNA in vitro. However, modification of the iron-sulfur cluster by hydrogen peroxide or nitric oxide does not significantly affect the DNA binding activity of RtelN, suggesting that the iron-sulfur cluster is not directly involved in the DNA interaction in the N-terminal domain of Rtel1. Aaron P. Landry and Huangen Ding Copyright © 2014 Aaron P. Landry and Huangen Ding. All rights reserved. Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease Thu, 24 Jul 2014 08:58:17 +0000 Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH. Amirmasoud Zangiabadi, Carmine G. De Pasquale, and Dimitar Sajkov Copyright © 2014 Amirmasoud Zangiabadi et al. All rights reserved. Antiviral Action of Synthetic Stigmasterol Derivatives on Herpes Simplex Virus Replication in Nervous Cells In Vitro Thu, 24 Jul 2014 08:56:54 +0000 Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied. Erina Petrera, Analía G. Níttolo, and Laura E. Alché Copyright © 2014 Erina Petrera et al. All rights reserved. Cationic Polyene Phospholipids as DNA Carriers for Ocular Gene Therapy Thu, 24 Jul 2014 08:54:19 +0000 Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy. Susana Machado, Sofia Calado, Diogo Bitoque, Ana Vanessa Oliveira, Christer L. Øpstad, Muhammad Zeeshan, Hans-Richard Sliwka, Vassilia Partali, Michael D. Pungente, and Gabriela A. Silva Copyright © 2014 Susana Machado et al. All rights reserved. The Parameters of Transcutaneous Electrical Nerve Stimulation Are Critical to Its Regenerative Effects When Applied Just after a Sciatic Crush Lesion in Mice Thu, 24 Jul 2014 07:56:08 +0000 We investigated the effect of two frequencies of transcutaneous electrical nerve stimulation (TENS) applied immediately after lesion on peripheral nerve regeneration after a mouse sciatic crush injury. The animals were anesthetized and subjected to crushing of the right sciatic nerve and then separated into three groups: nontreated, Low-TENS (4 Hz), and High-TENS (100 Hz). The animals of Low- and High-TENS groups were stimulated for 2 h immediately after the surgical procedure, while the nontreated group was only positioned for the same period. After five weeks the animals were euthanized, and the nerves dissected bilaterally for histological and histomorphometric analysis. Histological assessment by light and electron microscopy showed that High-TENS and nontreated nerves had a similar profile, with extensive signs of degeneration. Conversely, Low-TENS led to increased regeneration, displaying histological aspects similar to control nerves. High-TENS also led to decreased density of fibers in the range of 6–12 μm diameter and decreased fiber diameter and myelin area in the range of 0–2 μm diameter. These findings suggest that High-TENS applied just after a peripheral nerve crush may be deleterious for regeneration, whereas Low-TENS may increase nerve regeneration capacity. Diana Cavalcante Miranda de Assis, Êmyle Martins Lima, Bruno Teixeira Goes, João Zugaib Cavalcanti, Alaí Barbosa Paixão, Marcos André Vannier-Santos, Ana Maria Blanco Martinez, and Abrahão Fontes Baptista Copyright © 2014 Diana Cavalcante Miranda de Assis et al. All rights reserved. Diagnostic and Prognostic Value of Soluble Syndecan-1 in Pleural Malignancies Thu, 24 Jul 2014 07:55:16 +0000 Background. The distinction between malignant and benign pleural effusions is a diagnostic challenge today and measuring soluble biomarkers could add to the diagnostic accuracy. Syndecan-1 is a proteoglycan involved in various cellular functions and is cleaved from the cell surface in a regulated manner. The shed fragment, which can be recovered in effusion supernatant and in serum, retains its binding capacities, but often with different functions and signalling properties than the cell-bound form. Aim. This study aimed to investigate the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera from patients with pleural malignancies. Study Design. Using two cohorts of patients, we assessed the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera, using enzyme-linked immunosorbent assays. Results. In pleural effusions, syndecan-1 distinguished malignant and benign diseases, with an odds ratio of 8.59 (95% CI 3.67 to 20.09). Furthermore, syndecan-1 in pleural effusions predicted a survival difference for patients with pleural metastatic disease and malignant mesothelioma of 11.2 and 9.2 months, respectively. However, no such effects were seen when syndecan-1 was measured in serum. Conclusion. Soluble syndecan-1 is a promising candidate biomarker for the cytopathological diagnosis and prognostication of malignant pleural effusions. Filip Mundt, Ghazal Heidari-Hamedani, Gustav Nilsonne, Muzaffer Metintas, Anders Hjerpe, and Katalin Dobra Copyright © 2014 Filip Mundt et al. All rights reserved. Security Mechanism Based on Hospital Authentication Server for Secure Application of Implantable Medical Devices Thu, 24 Jul 2014 07:55:14 +0000 After two recent security attacks against implantable medical devices (IMDs) have been reported, the privacy and security risks of IMDs have been widely recognized in the medical device market and research community, since the malfunctioning of IMDs might endanger the patient’s life. During the last few years, a lot of researches have been carried out to address the security-related issues of IMDs, including privacy, safety, and accessibility issues. A physician accesses IMD through an external device called a programmer, for diagnosis and treatment. Hence, cryptographic key management between IMD and programmer is important to enforce a strict access control. In this paper, a new security architecture for the security of IMDs is proposed, based on a 3-Tier security model, where the programmer interacts with a Hospital Authentication Server, to get permissions to access IMDs. The proposed security architecture greatly simplifies the key management between IMDs and programmers. Also proposed is a security mechanism to guarantee the authenticity of the patient data collected from IMD and the nonrepudiation of the physician’s treatment based on it. The proposed architecture and mechanism are analyzed and compared with several previous works, in terms of security and performance. Chang-Seop Park Copyright © 2014 Chang-Seop Park. All rights reserved. The Relationship between Specific Cognitive Domains, Fear of Falling, and Falls in People with Multiple Sclerosis Thu, 24 Jul 2014 07:33:21 +0000 The primary aim was to examine the relationship between seven definite aspects of cognition measured by a computerized cognitive testing tool on the history falls in people with mild to moderate MS (PwMS). Secondary aims focused on whether cognition performance is correlated to fear of falling, walking velocity, and a patient-rated measure of walking ability. One hundred and one PwMS were included in the study analysis. Fifty-two had a history of at least one fall during the past year. Outcome measures included a computerized cognitive test battery designed to evaluate multiple cognitive domains, gait speed, and self-reported questionnaires; 12-item MS walking scale (MSWS-12); and Falls Efficacy Scale International. Significant differences between fallers and nonfallers were exhibited in attention and verbal function, scoring 7.5% () and 6.2% (), respectively, below the parallel scores of the nonfallers. Attention was the only cognitive component significantly correlated with the MSWS-12 self-reported questionnaire. Fear of falling was significantly correlated with 6 (out of 7) definite cognitive variables. The present findings support the concept that when evaluating and attempting to reduce fall risk, emphasis should be placed not only on traditional fall risk factors like muscle strength and motor function, but also on cognitive function. Alon Kalron Copyright © 2014 Alon Kalron. All rights reserved. The Evolution of Legislation in the Field of Medically Assisted Reproduction and Embryo Stem Cell Research in European Union Members Thu, 24 Jul 2014 07:18:37 +0000 Medically Assisted Reproduction (MAR), involving in vitro fertilisation (IVF), and research on embryos have created expectation to many people affected by infertility; at the same time it has generated a surplus of laws and ethical and social debates. Undoubtedly, MAR represents a rather new medical field and constant developments in medicine and new opportunities continue to defy the attempt to respond to those questions. In this paper, the authors reviewed the current legislation in the 28 EU member states trying to evaluate the different legislation paths adopted over the last 15 years and highlighting those EU countries with no specific legislation in place and MAR is covered by a general health Law and those countries in which there are no laws in this field but only “guidelines.” The second aim of this work has been to compare MAR legislation and embryo research in EU countries, which derive from different origins ranging from an extremely prohibitive approach versus a liberal one, going through a cautious regulatory approach. Francesco Paolo Busardò, Matteo Gulino, Simona Napoletano, Simona Zaami, and Paola Frati Copyright © 2014 Francesco Paolo Busardò et al. All rights reserved. Tailored PVA/ECM Scaffolds for Cartilage Regeneration Thu, 24 Jul 2014 07:17:01 +0000 Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to design in vitro a supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM), which is decellularized Wharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA). Wharton’s jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton’s jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration. Elena Stocco, Silvia Barbon, Daniele Dalzoppo, Silvano Lora, Leonardo Sartore, Marcella Folin, Pier Paolo Parnigotto, and Claudio Grandi Copyright © 2014 Elena Stocco et al. All rights reserved. Repeated Batch Fermentation Biotechnology for the Biosynthesis of Lipid and Gamma-Linolenic Acid by Cunninghamella bainieri 2A1 Thu, 24 Jul 2014 07:09:16 +0000 The biosynthesis of biomedical products including lipid and gamma-linolenic acid (GLA) by Cunninghamella bainieri 2A1 was studied in repeated batch fermentation. Three key process variables, namely, glucose concentration, ammonium tartrate concentration, and harvesting time, were optimized using response surface methodology. Repeated batch fermentation was carried out by the cultivation of Cunninghamella bainieri 2A1 in nitrogen-limited medium with various nitrogen concentration (1–4 g/L) and glucose concentration (20–40 g/L) at three time intervals (12 h, 24 h, and 48 h). Experimental results showed that the highest lipid concentration of 6.2 g/L and the highest GLA concentration of 0.4 g/L were obtained in optimum conditions, where 20.2 g/L glucose, 2.12 g/L ammonium tartrate, and 48 h harvesting time were utilized. Statistical results showed that the interaction between glucose and ammonium tartrate concentration had highly significant effects on lipid and GLA biosynthesis (). Moreover, harvesting time had a significant interaction effect with glucose and ammonium tartrate concentration on lipid production (). Marjan Ganjali Dashti, Peyman Abdeshahian, Wan Mohtar Wan Yusoff, Mohd Sahaid Kalil, and Aidil Abdul Hamid Copyright © 2014 Marjan Ganjali Dashti et al. All rights reserved. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart Thu, 24 Jul 2014 06:41:21 +0000 The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. Sarai Limon-Miranda, Diana G. Salazar-Enriquez, Jesus Muñiz, Mario V. Ramirez-Archila, Enrique A. Sanchez-Pastor, Felipa Andrade, Jose G. Soñanez-Organis, Edgar F. Moran-Palacio, and Adolfo Virgen-Ortiz Copyright © 2014 Sarai Limon-Miranda et al. All rights reserved. Heat Shock Proteins at the Crossroads between Cancer and Alzheimer’s Disease Thu, 24 Jul 2014 06:37:47 +0000 Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90) have been implicated in many crucial steps of carcinogenesis: stabilizing oncogenic proteins, inhibiting programmed cell death and replicative senescence, induction of tumor angiogenesis, and activation of the invasion and metastasis. Plenty of cancer related proteins have the ability of regulating the expression of Hsp70/90 through heat shock factor 1. Cancer and Alzheimer’s disease (AD) have plenty of overlapping regions in molecular genetics and cell biology associated with Hsp70/90. The Hsp70, as a protein stabilizer, has a cellular protection against neurodegeneration of the central nervous system, while Hsp90 promote neurodegenerative disorders indirectly through regulating the expression of Hsp70 and other chaperones. All these make existing anticancer drugs target Hsp70/90 which might be used in AD therapy. Hao Wang, Meng-Shan Tan, Rui-Chun Lu, Jin-Tai Yu, and Lan Tan Copyright © 2014 Hao Wang et al. All rights reserved. New Perspectives on Antiacne Plant Drugs: Contribution to Modern Therapeutics Thu, 24 Jul 2014 00:00:00 +0000 Acne is a common but serious skin disease, which affects approximately 80% adolescents and young adults in 11–30 age group. 42.5% of men and 50.9% of women continue to suffer from this disease into their twenties. Bacterial resistance is now at the alarming stage due to the irrational use of antibiotics. Hence, search for new lead molecule/bioactive and rational delivery of the existing drug (for better therapeutic effect) to the site of action is the need of the hour. Plants and plant-derived products have been an integral part of health care system since time immemorial. Therefore, plants that are currently used for the treatment of acne and those with a high potential are summarized in the present review. Most active plant extracts, namely, P. granatum, M. alba, A. anomala, and M. aquifolium exhibit minimum inhibitory concentration (MIC) in the range of 4–50 µg/mL against P. acnes, while aromatic oils of C. obovoides, C. natsudaidai, C. japonica, and C. nardus possess MICs 0.005–0.6 μL/mL and phytomolecules such as rhodomyrtone, pulsaquinone, hydropulsaquinone, honokiol, magnolol, xanthohumol lupulones, chebulagic acid and rhinacanthin-C show MIC in the range of 0.5–12.5 μg/mL. Novel drug delivery strategies of important plant leads in the treatment of acne have also been discussed. Priyam Sinha, Shruti Srivastava, Nidhi Mishra, and Narayan Prasad Yadav Copyright © 2014 Priyam Sinha et al. All rights reserved. Differences in Cytotoxic, Genotoxic, and Inflammatory Response of Bronchial and Alveolar Human Lung Epithelial Cells to Pristine and COOH-Functionalized Multiwalled Carbon Nanotubes Thu, 24 Jul 2014 00:00:00 +0000 Functionalized MWCNTs are used in many commercial and biomedical applications, but their potential health effects are not well defined. We investigated and compared cytotoxic, genotoxic/oxidative, and inflammatory effects of pristine and carboxyl MWCNTs exposing human respiratory (A549 and BEAS-2B) cells to 1–40 μg/mL of CNTs for 24 h. Both MWCNTs induced low viability reduction (by WST1 assay) in A549 cells and only MWCNTs-COOH caused high viability reduction in BEAS-2B cells reaching 28.5% viability at 40 μg/mL. Both CNTs induced membrane damage (by LDH assay) with higher effects in BEAS-2B cells at the highest concentrations reaching 20% cytotoxicity at 40 μg/mL. DNA damage (by Fpg-comet assay) was induced by pristine MWCNTs in A549 cells and by both MWCNTs in BEAS-2B cells reaching for MWCNTs-COOH a tail moment of 22.2 at 40 μg/mL versus 10.2 of unexposed cells. Increases of IL-6 and IL-8 release (by ELISA) were detected in A549 cells exposed to MWCNTs-COOH from 10 μg/mL while IL-8 increased in BEAS-2B cells exposed to pristine MWCNTs at 20 and 40 μg/mL. The results show higher cytogenotoxicity of MWCNTs-COOH in bronchial and of pristine MWCNTs in alveolar cells. Different inflammatory response was also found. The findings suggest the use of in vitro models with different end points and cells to study CNT toxicity. Cinzia Lucia Ursini, Delia Cavallo, Anna Maria Fresegna, Aureliano Ciervo, Raffaele Maiello, Giuliana Buresti, Stefano Casciardi, Stefano Bellucci, and Sergio Iavicoli Copyright © 2014 Cinzia Lucia Ursini et al. All rights reserved. Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients Thu, 24 Jul 2014 00:00:00 +0000 Background. Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress. Methods. Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2. Results. 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count , and reductions in levels of C-reactive protein , and total indoxyl glucuronide , . No statistically significant changes were observed in other uremic toxin levels or measures of QOL. Conclusions. Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power—further studies are warranted. Ranganathan Natarajan, Bohdan Pechenyak, Usha Vyas, Pari Ranganathan, Alan Weinberg, Peter Liang, Mary C. Mallappallil, Allen J. Norin, Eli A. Friedman, and Subodh J. Saggi Copyright © 2014 Ranganathan Natarajan et al. All rights reserved.