BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. In Vitro Larvicidal and Antioxidant Activity of Dihydrophenanthroline-3-carbonitriles Thu, 24 Apr 2014 14:12:05 +0000 Many naturally occurring and synthetic compounds containing dihydrocyanopyridine and cyanopyran moiety show pharmacological properties. The aim of this study is to investigate the larvicidal and antioxidant potential of dihydrophenanthroline-3-carbonitrile derivatives 4a–f. A novel series of 2-amino-10-chloro-4,12-diphenyl-1,4,5,6-tetrahydrobenzo[j][1,7]phenanthroline-3-carbonitrile derivatives were synthesized by reacting different substituted acridine chalcones through Michel addition. The compounds were synthesized in excellent yields and the structures were corroborated on the basis of FT-IR, 1H NMR, 13C NMR, and ESI Mass analysis data. All the synthesized compounds were evaluated for larvicidal activity against Aedes aegypti and Culex quinquefasciatus larvae. Furthermore, the antioxidant activity was studied by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay method. From the antioxidant assay, the compound 4c was reported with profound antioxidant potential. A. Bharathi, Selvaraj Mohana Roopan, Abdul Abdul Rahuman, and Govindasamy Rajakumar Copyright © 2014 A. Bharathi et al. All rights reserved. Oxidative Stress Indicators in Patients with Prostate Disorders in Enugu, South-East Nigeria Thu, 24 Apr 2014 13:47:34 +0000 Depletion of cellular antioxidants can result from free radical formation due to normal endogenous reactions and the ingestion of exogenous substances and environmental factors. The levels of reactive oxygen species-(ROS-) scavenging enzymes such as SOD and glutathione peroxidase have been shown to be significantly altered in malignant cells and in primary cancer tissues. The aim of this study was to determine the antioxidant status of patients with prostate disorders in South-East Nigeria to ascertain the possible role of depletion of antioxidants in prostatic degeneration. 104 subjects made up of 40 PCa patients, 32 with BPH, and 32 controls participated in this study. The levels of superoxide dismutase, glutathione peroxidase, vitamin C, and vitamin E were estimated using standard procedures. The results show that both the BPH and PCa patients had a significant decrease () in GPX, SOD, vitamin C, and vitamin E levels compared to the control subjects. However, there was also a significant decrease () in SOD and vitamin C levels in PCa patients when compared with the BPH group. This indicates that patients with BPH and prostate cancer have decreased antioxidant status and may benefit from micronutrient supplementation. Romanda Duru, Obioma Njoku, and Ignatius Maduka Copyright © 2014 Romanda Duru et al. All rights reserved. Tumor and Endothelial Cell Hybrids Participate in Glioblastoma Vasculature Thu, 24 Apr 2014 12:57:01 +0000 Background. Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM). Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM. Materials and Methods. We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact. Results. In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF). By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation. Conclusion. A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance. Soufiane El Hallani, Carole Colin, Younas El Houfi, Ahmed Idbaih, Blandine Boisselier, Yannick Marie, Philippe Ravassard, Marianne Labussière, Karima Mokhtari, Jean-Léon Thomas, Jean-Yves Delattre, Anne Eichmann, and Marc Sanson Copyright © 2014 Soufiane El Hallani et al. All rights reserved. IDH1/IDH2 but Not TP53 Mutations Predict Prognosis in Bulgarian Glioblastoma Patients Thu, 24 Apr 2014 12:53:22 +0000 Mutations in genes encoding isocitrate dehydrogenase isoforms 1 (IDH1) and 2 (IDH2) have been associated with good prognosis for patients with brain neoplasias and have been commonly found together with mutated TP53 gene. To determine the prevalence of IDH1, IDH2, and TP53 mutations and their impact on overall survival 106 glioblastoma patients were analysed. IDH1 mutations were detected in 13 and IDH2 mutation in one patient. Two homozygous samples with R132H mutation in IDH1 gene and a novel aberration K129R in IDH2 gene were found. Sixty-four percent of IDH1/IDH2 mutated tumours harboured also a mutation in TP53 gene. Genetic aberrations in TP53 were present in 37 patients. Statistical analysis of the impact of the studied factors on the overall survival showed that the mutations in IDH1/IDH2, but not the ones in TP53, were associated with longer survival. Also, the impact of age on prognosis was confirmed. This is the first comprehensive study on glioblastomas in Bulgaria. Our results suggest that IDH1/IDH2 but not TP53 mutations together with other prognostic factors such as age might be applied in clinical practice for prediction of outcome in patients with glioblastomas. Gergana Stancheva, Teodora Goranova, Maria Laleva, Margarita Kamenova, Atanaska Mitkova, Nikolay Velinov, George Poptodorov, Vanio Mitev, Radka Kaneva, and Nikolay Gabrovsky Copyright © 2014 Gergana Stancheva et al. All rights reserved. Experience of Preimplantation Genetic Diagnosis with HLA Matching at the University Hospital Virgen del Rocío in Spain: Technical and Clinical Overview Thu, 24 Apr 2014 12:39:43 +0000 Preimplantation genetic diagnosis (PGD) of genetic diseases, combined with HLA matching (PGD-HLA), is an option for couples at risk of transmitting a genetic disease to select unaffected embryos of an HLA tissue type compatible with that of an existing affected child. Here we present the results of our PGD-HLA program at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocío in Seville. Seven couples have participated in our program because of different indications. Overall, 26 cycles were performed, providing a total of 202 embryos. A conclusive molecular diagnosis and HLA-typing could be assured in 96% of the embryos. The percentage of transfers per cycle was 26.9% and the birth rate per cycle was 7.7% per transfer. Our PGD-HLA program resulted in the birth of 2 healthy babies, HLA-identical to their affected siblings, with successful subsequent haematopoietic stem cell (HSC) transplantations. Both HSC-transplanted children are currently doing well 48 and 21 months following transplantation, respectively. All the procedures, including HSCs umbilical cord transplantation, were performed in our hospital. Raquel María Fernández, Ana Peciña, Maria Dolores Lozano-Arana, Beatriz Sánchez, Jordi Guardiola, Juan Carlos García-Lozano, Salud Borrego, and Guillermo Antiñolo Copyright © 2014 Raquel María Fernández et al. All rights reserved. The E3 Ligase CHIP: Insights into Its Structure and Regulation Thu, 24 Apr 2014 12:37:31 +0000 The carboxy-terminus of Hsc70 interacting protein (CHIP) is a cochaperone E3 ligase containing three tandem repeats of tetratricopeptide (TPR) motifs and a C-terminal U-box domain separated by a charged coiled-coil region. CHIP is known to function as a central quality control E3 ligase and regulates several proteins involved in a myriad of physiological and pathological processes. Recent studies have highlighted varied regulatory mechanisms operating on the activity of CHIP which is crucial for cellular homeostasis. In this review article, we give a concise account of our current knowledge on the biochemistry and regulation of CHIP. Indranil Paul and Mrinal K. Ghosh Copyright © 2014 Indranil Paul and Mrinal K. Ghosh. All rights reserved. Synthesis and Evaluation of Tetramethylguanidinium-Polyethylenimine Polymers as Efficient Gene Delivery Vectors Thu, 24 Apr 2014 12:23:40 +0000 Previously, we demonstrated that 6-(N,N,N′,N′-tetramethylguanidinium chloride)-hexanoyl-polyethylenimine (THP) polymers exhibited significantly enhanced transfection efficiency and cell viability. Here, in the present study, we have synthesized a series of N,N,N′,N′-tetramethylguanidinium-polyethylenimine (TP1-TP5) polymers via a single-step reaction involving peripheral primary amines of bPEI and varying amounts of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). These polymers were found to interact efficiently with negatively charged pDNA and formed stable complexes in the size range of ~240–450 nm. Acid-base titration profiles revealed improved buffering capacity of TP polymers as compared to bPEI. Transfection and cytotoxicity assays performed with TP/pDNA complexes on HEK293, CHO, and HeLa cells showed significantly higher transfection efficiency and cell viability with one of the complexes, TP2/pDNA complex, exhibited the highest transfection efficiency (~1.4–2.3-fold) outcompeting native bPEI and the commercially available transfection reagent, Lipofectamine 2000. Compared to previously reported THP polymers, the transfection efficiency of TP/pDNA complexes was found to be lower, as examined by flow cytometry. These results highlight the importance of the hydrophobic C-6 linker in THP polymers in forming compact nanostructures with pDNA, which might lead to efficient uptake and internalization of the complexes; however, the projected TP polymers offer an advantage of their rapid and economical one-step synthesis. Manohar Mahato, Santosh Yadav, Pradeep Kumar, and Ashwani Kumar Sharma Copyright © 2014 Manohar Mahato et al. All rights reserved. The Three Genetics (Nuclear DNA, Mitochondrial DNA, and Gut Microbiome) of Longevity in Humans Considered as Metaorganisms Thu, 24 Apr 2014 10:50:49 +0000 Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between nDNA/mtDNA and the environment is most likely involved in phenomena such as ageing and longevity. To this scenario we have to add another level of complexity represented by the microbiota, that is, the whole set of bacteria present in the different part of our body with their whole set of genes. In particular, several studies investigated the role of gut microbiota (GM) modifications in ageing and longevity and an age-related GM signature was found. In this view, human being must be considered as “metaorganism” and a more holistic approach is necessary to grasp the complex dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host during ageing. In this review, the relationship between the three genetics and human longevity is addressed to point out that a comprehensive view will allow the researchers to properly address the complex interactions that occur during human lifespan. Paolo Garagnani, Chiara Pirazzini, Cristina Giuliani, Marco Candela, Patrizia Brigidi, Federica Sevini, Donata Luiselli, Maria Giulia Bacalini, Stefano Salvioli, Miriam Capri, Daniela Monti, Daniela Mari, Sebastiano Collino, Massimo Delledonne, Patrick Descombes, and Claudio Franceschi Copyright © 2014 Paolo Garagnani et al. All rights reserved. Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Methanol Extract of Muntingia calabura L. Leaves Thu, 24 Apr 2014 09:43:43 +0000 Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations. N. D. Mahmood, S. S. Mamat, F. H. Kamisan, F. Yahya, M. F. F. Kamarolzaman, N. Nasir, N. Mohtarrudin, S. F. Md. Tohid, and Z. A. Zakaria Copyright © 2014 N. D. Mahmood et al. All rights reserved. Repeatability of Ocular Measurements with a Dual-Scheimpflug Analyzer in Healthy Eyes Thu, 24 Apr 2014 09:42:58 +0000 Purpose. To assess the repeatability of the Galilei dual Scheimpflug analyzer (GDSA) in anterior segment examination. Methods. Fifty-two eyes from 52 healthy volunteers were prospectively and consecutively recruited. Anatomic, axial, refractive, and instantaneous parameters were measured with GDSA to provide a complete characterization of the anterior segment. Repeatability was assessed calculating intraclass correlation coefficient (ICC), and coefficient of variation (COV). Results. Correlation among repeated measurements showed almost perfect reliability (ICC > 0.81) for all parameters except thinnest central corneal thickness (CCT) (0.78), corneal thickness average out (0.79), and posterior axial curvature average out (0.60). Repeatability was excellent (COV 10%) for all parameters except anterior chamber volume and, superior iridocorneal angle and eccentricities. In these last three parameters, repeatability limits were excessively high compared to the mean. Conclusions. GDSA in healthy young persons had an almost perfect correlation in measuring anatomic, axial, instantaneous, and refractive parameters with greater variability for peripheral terms. Repeatability of anatomical parameters like pachymetry, anterior chamber, or iridocorneal angle and eccentricity were limited. In healthy young persons, the other evaluated parameters had very good repeatability and their limits of agreement showed excellent clinical results for this device. Carmen Lopez de la Fuente, Ana Sanchez-Cano, Francisco Segura, Lorena Fuentes-Broto, and Isabel Pinilla Copyright © 2014 Carmen Lopez de la Fuente et al. All rights reserved. Kinematic Analysis of the Upper Limb Motor Strategies in Stroke Patients as a Tool towards Advanced Neurorehabilitation Strategies: A Preliminary Study Thu, 24 Apr 2014 09:37:23 +0000 Advanced rehabilitation strategies of the upper limb in stroke patients focus on the recovery of the most important daily activities. In this study we analyzed quantitatively and qualitatively the motor strategies employed by stroke patients when reaching and drinking from a glass. We enrolled 6 hemiparetic poststroke patients and 6 healthy subjects. Motion analysis of the task proposed (reaching for the glass, bringing it to the mouth, and putting it back on the table) with the affected limb was performed. Clinical assessment using the Fugl-Meyer Assessment for Upper Extremity was also included. During the reaching for the glass the patients showed a reduced arm elongation and trunk axial rotation due to motor deficit. For this reason, as observed, they carried out compensatory strategies which included trunk forward displacement and head movements. These preliminary data should be considered to address rehabilitation treatment. Moreover, the kinematic analysis protocol developed might represent an outcome measure of upper limb rehabilitation processes. Irene Aprile, Marco Rabuffetti, Luca Padua, Enrica Di Sipio, Chiara Simbolotti, and Maurizio Ferrarin Copyright © 2014 Irene Aprile et al. All rights reserved. The Association between Autoantibodies and Peripheral Neuropathy in Lupus Nephritis Thu, 24 Apr 2014 09:12:22 +0000 Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy. Methods. Data of 559 SLE-LN patients were collected retrospectively, including titers of autoantibodies, electrodiagnostic studies, and clinical manifestations. Results. The neurologic manifestations of the SLE-LN patients were diverse and nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional gastrointestinal problems were the most prevalent symptoms and these were noted in every subtype of peripheral neuropathy. Among all the serology markers, anti-Ro was significantly associated with neuropathy related to SLE (). Conclusion. Peripheral neuropathy among LN patients is rare and may be easily overlooked. This study demonstrated that positive anti-Ro antibody may imply neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that should be added to the panel of conventional autoantibodies in LN patients. Yu-Jih Su, Chi-Ren Huang, Wen-Neng Chang, Nai-Wen Tsai, Chia-Te Kung, Wei-Che Lin, Chih-Cheng Huang, Chih-Min Su, Ben-Chung Cheng, Ya-Ting Chang, and Cheng-Hsien Lu Copyright © 2014 Yu-Jih Su et al. All rights reserved. Efficacy of Physiotherapy for Urinary Incontinence following Prostate Cancer Surgery Thu, 24 Apr 2014 07:30:48 +0000 The study enrolled 81 with urinary incontinence following radical prostate-only prostatectomy for prostatic carcinoma. The patients were divided into two groups. The patients in Group I were additionally subdivided into two subgroups with respect to the physiotherapeutic method used. The patients of subgroup IA received a rehabilitation program consisting of three parts. The patients of subgroup IB rehabilitation program consist of two parts. Group II, a control group, had reported for therapy for persistent urinary incontinence following radical prostatectomy but had not entered therapy for personal reasons. For estimating the level of incontinence, a 1-hour and 24-hour urinary pad tests, the miction diary, and incontinence questionnaire were used, and for recording the measurements of pelvic floor muscles tension, the sEMG (surface electromyography) was applied. The therapy duration depended on the level of incontinence and it continued for not longer than 12 months. Superior continence outcomes were obtained in Group I versus Group II and the difference was statistically significant. The odds ratio for regaining continence was greater in the rehabilitated Group I and smaller in the group II without the rehabilitation. A comparison of continence outcomes revealed a statistically significant difference between Subgroups IA versus IB. The physiotherapeutic procedures applied on patients with urine incontinence after prostatectomy, for most of them, proved to be an effective way of acting, which is supported by the obtained results. Elżbieta Rajkowska-Labon, Stanisław Bakuła, Marek Kucharzewski, and Zbigniew Śliwiński Copyright © 2014 Elżbieta Rajkowska-Labon et al. All rights reserved. The Significance of Serum Phosphate Level on Healing Index and Its Relative Effects in Skeletally Immature and Mature Patients with Hypophosphatemic Rickets Thu, 24 Apr 2014 06:39:07 +0000 The aim of this study was to find out the ideal cut-off level of phosphate for safe healing when deformity correction and concomitant lengthening are indicated in the two different skeletal maturity groups of patients with rickets. Thirty-nine hypophosphatemic rickets patients were selected for the study and were divided into two groups: 27 skeletally immature (group IM) and 12 skeletally mature (group M). The outcomes were evaluated with respect to the healing index (HI), laboratory findings, and complications with the mean follow-up of 5.1 years (range, 3.1–7.9). The healing index (HI) of group IM was 1.44 month/cm and HI of group M was 1.68 month/cm. The negative correlation between the level of serum phosphate and HI in group M (coefficient = −0.94) was evaluated to be less than the correlation in group IM (coefficient = −0.50), indicating that the HI is more likely to be affected by serum phosphate in group M than in group IM. Preoperative serum phosphate levels of 2.3 mg/dL and 2.6 mg/dL were analyzed to be the cut-off values of group IM and group M, respectively, in which the cut-off points divided the series into two groups having the most significantly different HI. Sang-Heon Song, Hanna Lee, Ji-Min Jeong, Woo-In Cho, Sung Eun Kim, and Hae-Ryong Song Copyright © 2014 Sang-Heon Song et al. All rights reserved. Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow? Wed, 23 Apr 2014 16:30:34 +0000 Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates. Carlo Bastianelli, Manuela Farris, Stefania Rapiti, Roberta Bruno Vecchio, and Giuseppe Benagiano Copyright © 2014 Carlo Bastianelli et al. All rights reserved. Evaluation of Anti-Candida Activity of Vitis vinifera L. Seed Extracts Obtained from Wine and Table Cultivars Wed, 23 Apr 2014 14:44:43 +0000 For the first time, grape seed extracts (GSEs), obtained from wine and table cultivars of Vitis vinifera L., cultured in experimental fields of Lazio and Puglia regions of Italy and grown in different agronomic conditions, have been tested on 43 Candida species strains. We demonstrated a significant correlation between the content of the flavan-3-ols in GSEs extracts, with a polymerization degree ≥4, and anti-Candida activity. Moreover, we demonstrated that GSEs, obtained from plants cultured with reduced irrigation, showed a content of polymeric flavan-3-ols 250 mg/g with geometric mean MIC values between 5.7 and 20.2 mg/L against Candida albicans reference strains. GSE, showing 573 mg/g of polymeric flavan-3-ols, has been tested in an experimental murine model of vaginal candidiasis by using noninvasive in vivo imaging technique. The results pointed out a significant inhibition of Candida albicans load 5 days after challenge. These findings indicate that GSEs with high content of polymeric flavan-3-ols can be used in mucosal infection as vaginal candidiasis. Giovanna Simonetti, Anna Rita Santamaria, Felicia Diodata D'Auria, Nadia Mulinacci, Marzia Innocenti, Francesca Cecchini, Eva Pericolini, Elena Gabrielli, Simona Panella, Donato Antonacci, Anna Teresa Palamara, Anna Vecchiarelli, and Gabriella Pasqua Copyright © 2014 Giovanna Simonetti et al. All rights reserved. Robotic Upper Limb Rehabilitation after Acute Stroke by NeReBot: Evaluation of Treatment Costs Wed, 23 Apr 2014 14:43:09 +0000 Stroke is the first cause of disability. Several robotic devices have been developed for stroke rehabilitation. Robot therapy by NeReBot is demonstrated to be an effective tool for the treatment of poststroke paretic upper limbs, able to improve the activities of daily living of stroke survivors when used both as additional treatment and in partial substitution of conventional rehabilitation therapy in the acute and subacute phases poststroke. This study presents the evaluation of the costs related to delivering such therapy, in comparison with conventional rehabilitation treatment. By comparing several NeReBot treatment protocols, made of different combinations of robotic and nonrobotic exercises, we show that robotic technology can be a valuable and economically sustainable aid in the management of poststroke patient rehabilitation. Masiero Stefano, Poli Patrizia, Armani Mario, Gregorio Ferlini, Roberto Rizzello, and Giulio Rosati Copyright © 2014 Masiero Stefano et al. All rights reserved. Analysis of the Associations between Vitamin D and Albuminuria or β-Cell Function in Chinese Type 2 Diabetes Wed, 23 Apr 2014 14:11:04 +0000 Objective. To investigate the associations of 25-(OH)D and β-cell function or insulin resistance or albuminuria in Chinese type 2 diabetic patients. Methods. In total, 1408 type 2 diabetic patients without vitamin D supplement were included in this retrospective study. Results. Comparison between patients with and without 25-(OH)D deficiency indicated that, compared with patients with 25-(OH)D ≥ 50 nmol/L, patients with 25-(OH)D < 50 nmol/L showed a higher level of urine albumin-creatinine ratio (ACR) ( mg/g versus  mg/g). Multiple regression analysis indicated that 25-(OH)D was independently and negatively correlated with urine ACR (, 95%CI 0.972–0.999, ), adjusted by age, diabetic duration, HBP duration, SBP, HbA1c, creatinine, LDL-C, triglyceride, total cholesterol, and HDL-C. Compared with patients with normal level of urine ACR, patients with higher level of urine ACR showed a significant lower level of 25-(OH)D ( nmol/L versus  nmol/L, ). Analysis of the associations of 25-(OH)D and β-cell function or insulin resistance showed that 25-(OH)D may not correlate with β-cell function or insulin resistance. Conclusion. 25-(OH)D was independently associated with albuminuria in Chinese type 2 diabetic patients but was not associated with β-cell function or insulin resistance. Xiaoling Cai, Zhaoheng Hu, Ling Chen, Xueyao Han, and Linong Ji Copyright © 2014 Xiaoling Cai et al. All rights reserved. Computational Prediction of Protein Function Based on Weighted Mapping of Domains and GO Terms Wed, 23 Apr 2014 13:45:28 +0000 In this paper, we propose a novel method, SeekFun, to predict protein function based on weighted mapping of domains and GO terms. Firstly, a weighted mapping of domains and GO terms is constructed according to GO annotations and domain composition of the proteins. The association strength between domain and GO term is weighted by symmetrical conditional probability. Secondly, the mapping is extended along the true paths of the terms based on GO hierarchy. Finally, the terms associated with resident domains are transferred to host protein and real annotations of the host protein are determined by association strengths. Our careful comparisons demonstrate that SeekFun outperforms the concerned methods on most occasions. SeekFun provides a flexible and effective way for protein function prediction. It benefits from the well-constructed mapping of domains and GO terms, as well as the reasonable strategy for inferring annotations of protein from those of its domains. Zhixia Teng, Maozu Guo, Qiguo Dai, Chunyu Wang, Jin Li, and Xiaoyan Liu Copyright © 2014 Zhixia Teng et al. All rights reserved. Prevalence of HIV and Syphilis Infection among Men Who Have Sex with Men in China: A Meta-Analysis Wed, 23 Apr 2014 13:43:03 +0000 Objectives. To figure out the most current prevalence of HIV and syphilis in MSM in China. Methods. A meta-analysis was conducted on the studies searched through PubMed, CNKI, and Wanfang published between 1 January 2009 and 11 April 2013. Results. Eighty-four eligible studies, either in Chinese or in English, were included in this review. The pooled prevalence of HIV and syphilis infection in MSM in China was 6.5% and 11.2%, respectively. The subgroup analyses indicated that the prevalence of HIV infection was higher in the economically less developed cities than that in the developed cities (7.5% versus 6.1%, ). In contrast, the prevalence of syphilis infection was lower in less developed cities than in developed cities (8.6% versus 15.1%). Studies with a sample size smaller than 500 had a lower prevalence of HIV and syphilis infection than those with a sample size greater than 500 (5.9% versus 7.2% for HIV; 11.0% versus 11.5% for syphilis, respectively). Conclusions. HIV and syphilis infection are prevalent in MSM in China. The different prevalence of HIV and syphilis infection between developing and developed cities underscores the need to target prevention strategies based on economic conditions. Yunhua Zhou, Dongliang Li, Dabing Lu, Yuhua Ruan, Xiao Qi, and Ge Gao Copyright © 2014 Yunhua Zhou et al. All rights reserved. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo Wed, 23 Apr 2014 13:42:27 +0000 Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation. Shu-Ting Chan, Yi-Chin Lin, Cheng-Hung Chuang, Rong-Jen Shiau, Jiunn-Wang Liao, and Shu-Lan Yeh Copyright © 2014 Shu-Ting Chan et al. All rights reserved. Leczyme: A New Candidate Drug for Cancer Therapy Wed, 23 Apr 2014 13:40:28 +0000 Sialic acid-binding lectin (SBL), isolated from oocytes of Rana catesbeiana, is leczyme and has both lectin and ribonuclease (RNase) activities. A remarkable antitumor effect of SBL has also been reported. SBL agglutinates various kinds of tumor cells but not normal cells. SBL agglutination activity is not affected by mono- or oligosaccharides. However, SBL-induced agglutination and antitumor effects are inhibited by sialomucin but not asialomucin. In addition, SBL has very little effect on sialidase-treated cells. SBL causes cancer-selective induction of apoptosis by multiple signaling pathways, which target RNA. Synergistic antitumor effects with other molecules, such as tumor necrosis factor-related apoptosis ligand (TRAIL) and interferon-γ (IFN-γ), have been reported. Thus, SBL may be a novel candidate molecule for anticancer drug development. Sialoglycoconjugates on the tumor cell surface may be associated with lectin activity and antitumor effects of SBL. We review the properties of SBL, particularly its lectin, RNase, and antitumor activities, and comprehensively examine the potential application of SBL for clinical purposes. Takeo Tatsuta, Shigeki Sugawara, Kohta Takahashi, Yukiko Ogawa, Masahiro Hosono, and Kazuo Nitta Copyright © 2014 Takeo Tatsuta et al. All rights reserved. Microarray Analysis of Serum mRNA in Patients with Head and Neck Squamous Cell Carcinoma at Whole-Genome Scale Wed, 23 Apr 2014 12:26:03 +0000 With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’s value ) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease. Markéta Čapková, Jana Šáchová, Hynek Strnad, Michal Kolář, Miluše Hroudová, Martin Chovanec, Zdeněk Čada, Martin Šteffl, Jaroslav Valach, Jan Kastner, Čestmír Vlček, Karel Smetana Jr., and Jan Plzák Copyright © 2014 Markéta Čapková et al. All rights reserved. Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients Wed, 23 Apr 2014 12:09:35 +0000 Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT). Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower () in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher () for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT. Maurizio Valeriani, Alessia Carnevale, Linda Agolli, Paolo Bonome, Adelaide Montalto, Luca Nicosia, Mattia F. Osti, Vitaliana De Sanctis, Giuseppe Minniti, and Riccardo Maurizi Enrici Copyright © 2014 Maurizio Valeriani et al. All rights reserved. The Multifaceted Functions of CXCL10 in Cardiovascular Disease Wed, 23 Apr 2014 09:28:28 +0000 C-X-C motif ligand 10 (CXCL10), or interferon-inducible protein-10, is a small chemokine belonging to the CXC chemokine family. Its members are responsible for leukocyte trafficking and act on tissue cells, like endothelial and vascular smooth muscle cells. CXCL10 is secreted by leukocytes and tissue cells and functions as a chemoattractant, mainly for lymphocytes. After binding to its receptor CXCR3, CXCL10 evokes a range of inflammatory responses: key features in cardiovascular disease (CVD). The role of CXCL10 in CVD has been extensively described, for example for atherosclerosis, aneurysm formation, and myocardial infarction. However, there seems to be a discrepancy between experimental and clinical settings. This discrepancy occurs from differences in biological actions between species (e.g. mice and human), which is dependent on CXCL10 signaling via different CXCR3 isoforms or CXCR3-independent signaling. This makes translation from experimental to clinical settings challenging. Furthermore, the overall consensus on the actions of CXCL10 in specific CVD models is not yet reached. The purpose of this review is to describe the functions of CXCL10 in different CVDs in both experimental and clinical settings and to highlight and discuss the possible discrepancies and translational difficulties. Furthermore, CXCL10 as a possible biomarker in CVD will be discussed. Pleunie van den Borne, Paul H. A. Quax, Imo E. Hoefer, and Gerard Pasterkamp Copyright © 2014 Pleunie van den Borne et al. All rights reserved. Kinematic Metrics Based on the Virtual Reality System Toyra as an Assessment of the Upper Limb Rehabilitation in People with Spinal Cord Injury Wed, 23 Apr 2014 09:27:05 +0000 The aim of this study was to develop new strategies based on virtual reality that can provide additional information to clinicians for the rehabilitation assessment. Virtual reality system Toyra has been used to record kinematic information of 15 patients with cervical spinal cord injury (SCI) while performing evaluation sessions using the mentioned system. Positive correlation, with a moderate and very strong association, has been found between clinical scales and kinematic data, considering only the subscales more closely related to the upper limb function. A set of metrics was defined combining these kinematic data to obtain parameters of reaching amplitude, joint amplitude, agility, accuracy, and repeatability during the evaluation sessions of the virtual reality system Toyra. Strong and moderate correlations have been also found between the metrics reaching and joint amplitude and the clinical scales. Fernando Trincado-Alonso, Iris Dimbwadyo-Terrer, Ana de los Reyes-Guzmán, Patricia López-Monteagudo, Alberto Bernal-Sahún, and Ángel Gil-Agudo Copyright © 2014 Fernando Trincado-Alonso et al. All rights reserved. Endocannabinoid Receptors Gene Expression in Morbidly Obese Women with Nonalcoholic Fatty Liver Disease Wed, 23 Apr 2014 09:25:55 +0000 Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD. Methods. We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL, ), simple steatosis (SS, ), and nonalcoholic steatohepatitis (NASH, ) by enzyme-linked immunosorbent assay and RT-PCR. Results. We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin. Conclusions. The increased expression of CB1 in NASH and the negative correlation with PPARα suggest a deleterious role of CB1 in NAFLD. Regarding CB2, its positive correlation with the anti-inflammatory molecule adiponectin and, paradoxically, with inflammatory genes suggests that this receptor has a dual role. Taken together, our results suggest that endocannabinoid receptors might be involved in the pathogenesis of NAFLD, a finding which justifies further study. Teresa Auguet, Alba Berlanga, Esther Guiu-Jurado, Ximena Terra, Salomé Martinez, Carmen Aguilar, Elisa Filiu, Ajla Alibalic, Fàtima Sabench, Mercé Hernández, Daniel Del Castillo, and Cristóbal Richart Copyright © 2014 Teresa Auguet et al. All rights reserved. Novel Design Strategy for Checkpoint Kinase 2 Inhibitors Using Pharmacophore Modeling, Combinatorial Fusion, and Virtual Screening Wed, 23 Apr 2014 09:23:00 +0000 Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set () with the value 0.816 by combining the and prediction results. The potential inhibitors were selected from NCI database by screening according to + prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study. Chun-Yuan Lin and Yen-Ling Wang Copyright © 2014 Chun-Yuan Lin and Yen-Ling Wang. All rights reserved. Effects of Canonical NF-κB Signaling Pathway on the Proliferation and Odonto/Osteogenic Differentiation of Human Stem Cells from Apical Papilla Wed, 23 Apr 2014 08:58:19 +0000 Background Information. NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-κB pathway on the osteo/odontogenic capacity of SCAPs in vitro. Results. Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-α or blocked by BMS-345541. NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF-κB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP-1/DMP-1) in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-κB pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups. Conclusion. Our findings suggest that classical NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs. Junjun Li, Ming Yan, Zilu Wang, Shuanglin Jing, Yao Li, Genxia Liu, Jinhua Yu, and Zhipeng Fan Copyright © 2014 Junjun Li et al. All rights reserved. High Level of Tregs Is a Positive Prognostic Marker in Patients with HPV-Positive Oral and Oropharyngeal Squamous Cell Carcinomas Wed, 23 Apr 2014 07:44:25 +0000 Background. Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. Material and Methods. Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. Results. Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. Conclusion. Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence. E. Lukesova, J. Boucek, E. Rotnaglova, M. Salakova, E. Koslabova, M. Grega, T. Eckschlager, B. Rihova, B. Prochazka, J. Klozar, and R. Tachezy Copyright © 2014 E. Lukesova et al. All rights reserved.