BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Cyclophilin A Interacts with Viral VP4 and Inhibits the Replication of Infectious Bursal Disease Virus Sun, 24 May 2015 12:14:27 +0000 Nonstructural protein VP4, a serine protease of infectious bursal disease virus (IBDV) that catalyzes the hydrolysis of polyprotein pVP2-VP4-VP3 to form the viral proteins VP2, VP4, and VP3, is essential to the replication of IBDV. However, the interacting partners of VP4 in host cells and the effects of the interaction on the IBDV lifecycle remain incompletely elucidated. In this study, using the yeast two-hybrid system, the putative VP4-interacting partner cyclophilin A (CypA) was obtained from a chicken embryo fibroblast (CEF) expression library. CypA was further confirmed to interact with VP4 of IBDV using co-immunoprecipitation (CO-IP), GST pull-down, and confocal microscopy assays. Moreover, we found that the overexpression of CypA suppressed IBDV replication, whereas the knock-down of CypA by small interfering RNAs promoted the replication of IBDV. Taken together, our findings indicate that the host cell protein CypA interacts with viral VP4 and inhibits the replication of IBDV. Nian Wang, Lizhou Zhang, Yuming Chen, Zhen Lu, Li Gao, Yongqiang Wang, Yulong Gao, Honglei Gao, Hongyu Cui, Kai Li, Changjun Liu, Yanping Zhang, Xiaole Qi, and Xiaomei Wang Copyright © 2015 Nian Wang et al. All rights reserved. High Intensity Interval Training Favourably Affects Angiotensinogen mRNA Expression and Markers of Cardiorenal Health in a Rat Model of Early-Stage Chronic Kidney Disease Sun, 24 May 2015 06:24:42 +0000 The majority of CKD-related complications stem from cardiovascular pathologies such as hypertension. To help reduce cardiovascular complications, aerobic exercise is often prescribed. Emerging evidence suggests high intensity interval training (HIIT) may be more beneficial than traditional aerobic exercise. However, appraisals of varying forms of aerobic exercise, along with descriptions of mechanisms responsible for health-related improvements, are lacking. This study examined the effects of 8 weeks of HIIT (85% VO2max), versus low intensity aerobic exercise (LIT; 45–50% VO2max) and sedentary behaviour (SED), in an animal model of early-stage CKD. Tissue-specific mRNA expression of RAAS-related genes and CKD-related clinical markers were examined. Compared to SED, HIIT resulted in increased plasma albumin (), reduced remnant kidney weight (), and reduced kidney weight-body weight ratios (). Compared to LIT, HIIT resulted in reduced Agt mRNA expression (), reduced plasma LDL (), triglycerides (), and total cholesterol (), increased plasma albumin (), reduced remnant kidney weight (), and reduced kidney weight-body weight ratios (). These results suggest HIIT is a more potent regulator of several markers that describe and influence health in CKD. Patrick S. Tucker, Aaron T. Scanlan, and Vincent J. Dalbo Copyright © 2015 Patrick S. Tucker et al. All rights reserved. Physical Activity in Hemodialysis Patients Measured by Triaxial Accelerometer Sun, 24 May 2015 06:16:45 +0000 Different factors can contribute to a sedentary lifestyle among hemodialysis (HD) patients, including the period they spend on dialysis. The aim of this study was to evaluate characteristics of physical activities in daily life in this population by using an accurate triaxial accelerometer and to correlate these characteristics with physiological variables. Nineteen HD patients were evaluated using the DynaPort accelerometer and compared to nineteen control individuals, regarding the time spent in different activities and positions of daily life and the number of steps taken. HD patients were more sedentary than control individuals, spending less time walking or standing and spending more time lying down. The sedentary behavior was more pronounced on dialysis days. According to the number of steps taken per day, 47.4% of hemodialysis patients were classified as sedentary against 10.5% in control group. Hemoglobin level, lower extremity muscle strength, and physical functioning of SF-36 questionnaire correlated significantly with the walking time and active time. Looking accurately at the patterns of activity in daily life, HDs patients are more sedentary, especially on dialysis days. These patients should be motivated to enhance the physical activity. Edimar Pedrosa Gomes, Maycon Moura Reboredo, Erich Vidal Carvalho, Daniel Rodrigues Teixeira, Laís Fernanda Caldi d’Ornellas Carvalho, Gilberto Francisco Ferreira Filho, Julio César Abreu de Oliveira, Helady Sanders-Pinheiro, Júlio Maria Fonseca Chebli, Rogério Baumgratz de Paula, and Bruno do Valle Pinheiro Copyright © 2015 Edimar Pedrosa Gomes et al. All rights reserved. Precursor Amino Acids Inhibit Polymyxin E Biosynthesis in Paenibacillus polymyxa, Probably by Affecting the Expression of Polymyxin E Biosynthesis-Associated Genes Thu, 21 May 2015 15:59:05 +0000 Polymyxin E belongs to cationic polypeptide antibiotic bearing four types of direct precursor amino acids including L-2,4-diaminobutyric acid (L-Dab), L-Leu, D-Leu, and L-Thr. The objective of this study is to evaluate the effect of addition of precursor amino acids during fermentation on polymyxin E biosynthesis in Paenibacillus polymyxa. The results showed that, after 35 h fermentation, addition of direct precursor amino acids to certain concentration significantly inhibited polymyxin E production and affected the expression of genes involved in its biosynthesis. L-Dab repressed the expression of polymyxin synthetase genes pmxA and pmxE, as well as 2,4-diaminobutyrate aminotransferase gene ectB; both L-Leu and D-Leu repressed the pmxA expression. In addition, L-Thr affected the expression of not only pmxA, but also regulatory genes spo0A and abrB. As L-Dab precursor, L-Asp repressed the expression of ectB, pmxA, and pmxE. Moreover, it affected the expression of spo0A and abrB. In contrast, L-Phe, a nonprecursor amino acid, had no obvious effect on polymyxin E biosynthesis and those biosynthesis-related genes expression. Taken together, our data demonstrated that addition of precursor amino acids during fermentation will inhibit polymyxin E production probably by affecting the expression of its biosynthesis-related genes. Zhiliang Yu, Chenglin Guo, and Juanping Qiu Copyright © 2015 Zhiliang Yu et al. All rights reserved. The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis Thu, 21 May 2015 15:58:19 +0000 Osteoarthritis (OA) is becoming a major public health problem in China, especially considering the increase in average life expectancy of the population. Thus, enhanced understanding of the molecular changes associated with OA is urgently needed to develop more effective strategies for the diagnosis and treatment of this debilitating disease. LncRNAs play an important role in the processes of bone and cartilage development. Maternally expressed gene 3 (MEG3) is a maternally expressed lncRNA and may function as a tumor suppressor by inhibiting angiogenesis. OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. In this study, we detected the mRNA expression of MEG3 and VEGF in articular cartilage samples from 20 OA patients and 10 healthy volunteers by real-time RT-PCR. VEGF protein is detected by ELISA in cartilage samples. The results show that human MEG3 is significantly downregulated in OA patients compared to normal cartilage samples. However, higher levels of VEGF mRNA and protein are found in OA compared to the control. Moreover, MEG3 levels are inversely associated with VEGF levels, suggesting that MEG3 may be involved in OA development through the regulation of angiogenesis. Wei Su, Wen Xie, Qingkun Shang, and Bing Su Copyright © 2015 Wei Su et al. All rights reserved. Antiedematogenic Evaluation of Copaifera langsdorffii Leaves Hydroethanolic Extract and Its Major Compounds Thu, 21 May 2015 14:33:38 +0000 Inflammatory disorders affect many people worldwide, and medicinal plants are used to ameliorate these health problems. This paper reports the antiedematogenic and analgesic evaluation of Copaifera langsdorffii Desf. leaves hydroethanolic extract (Cop) and two of its isolated compounds: quercetin-3-O-α-L-rhamnopyranosyl (quercitrin) and kaempferol-3-O-α-L-rhamnopyranosyl (afzelin). For that, the following experimental protocols were undertaken locomotor performance, writhing induced by acetic acid, antinociceptivity induced by formalin, hot plate latency, paw oedema induced by carrageenan and dextran, and cell migration induced by lipopolysaccharide (LPS), as well as the measurement of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) in macrophages. Neither the extract nor the isolated compounds displayed analgesic activity. The obtained results showed that C. langsdorffii extract possesses antiedematogenic properties acting on peripheral sites, whereas quercitrin and afzelin are not involved. Moreover, these properties are not associated with cell migration inhibition, TNF-α, IL-6, or IL-10 regulation. Ricardo Andrade Furtado, Cristiane Teixeira Vilhena Bernardes, Mauro Nogueira da Silva, Karina Furlani Zoccal, Lúcia Helena Faccioli, and Jairo Kenupp Bastos Copyright © 2015 Ricardo Andrade Furtado et al. All rights reserved. Prevention of Polyglycolic Acid-Induced Peritoneal Adhesions Using Alginate in a Rat Model Thu, 21 May 2015 14:18:05 +0000 Postoperative intra-abdominal or intrathoracic adhesions sometimes cause significant morbidity. We have designed three types of alginate-based treatments using strongly cross-linked (SL), weakly cross-linked (WL), and non-cross-linked (NL) alginate with calcium gluconate. In rat experiments, we compared the antiadhesive effects of the three types of alginate-based treatments, fibrin glue treatment (a standard treatment), and no treatment against adhesions caused by polyglycolic acid (PGA) mesh (PGA-induced adhesions). The antiadhesive materials were set on the PGA sheet fixed on the parietal peritoneum of the abdomen. Fifty-six days later, the adhesions were evaluated macroscopically by the adhesion scores and microscopically by hematoxylin-eosin staining and immunostaining. We also tested the fibroblast growth on the surface of the antiadhesive materials in vitro. The antiadhesive effects of WL and NL were superior to the no treatment and fibrin glue treatment. A microscopic evaluation confirmed that the PGA sheet was covered by a peritoneal layer constructed of well-differentiated mesothelial cells, and the inflammation was most improved in the NL and WL. The fibroblast growth was inhibited most on the surfaces of the NL and WL. These results suggest that either the WL or NL treatments are suitable for preventing PGA-induced adhesions compared to SL or the conventional treatment. Mari Matoba, Ayumi Hashimoto, Ayumi Tanzawa, Taichi Orikasa, Junki Ikeda, Yoshizumi Iwame, Yuki Ozamoto, Rie Abe, Hiroe Miyamoto, Chiko Yoshida, Toru Hashimoto, Hiroko Torii, Hideki Takamori, Shinichiro Morita, Hiroyuki Tsujimoto, and Akeo Hagiwara Copyright © 2015 Mari Matoba et al. All rights reserved. CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice Thu, 21 May 2015 13:46:17 +0000 Antibody-based imaging agents are attractive as adjuvant diagnostic tools for solid tumors. GPA33 is highly expressed in most human colorectal cancers and has been verified as a diagnostic and therapeutic target. Here, we built an A33scFv-Fc antibody against GPA33 by fusing A33scFv to the Fc fragment of human IgG1 antibodies. The A33scFv-Fc specifically binds GPA33-positive colorectal cancer cells and tumor tissues. After the intravenous injection of mice bearing subcutaneous GPA33-positive LS174T tumor grafts with near-infrared fluorescence probe CF750-labeled A33scFv-Fc (CF750-A33scFv-Fc), high contrast images of the tumor grafts could be kinetically documented within 24 h using an optical imaging system. However, GPA33-negative SMMC7721 tumor grafts could not be visualized by injecting the same amount of CF750-A33scFv-Fc. Moreover, in subcutaneous LS174T tumor-bearing mice, tissue scanning revealed that the CF750-A33scFv-Fc accumulated in the tumor grafts, other than the kidney and liver. In mice with orthotopic tumor transplantations, excrescent LS174T tumor tissues in the colon were successfully removed under guidance by CF750-A33scFv-Fc-based optical imaging. These results indicate that CF750-A33scFv-Fc can target GPA33, suggesting the potential of CF750-A33scFv-Fc as an imaging agent for the diagnosis of colorectal cancer. Danfeng Wei, Qing Fan, Huawei Cai, Hao Yang, Lin Wan, Lin Li, and Xiaofeng Lu Copyright © 2015 Danfeng Wei et al. All rights reserved. Effect of Fe3O4 Nanoparticles on Skin Tumor Cells and Dermal Fibroblasts Thu, 21 May 2015 13:03:13 +0000 Iron oxide (Fe3O4) nanoparticles have been used in many biomedical approaches. The toxicity of Fe3O4 nanoparticles on mammalian cells was published recently. Though, little is known about the viability of human cells after treatment with Fe3O4 nanoparticles. Herein, we examined the toxicity, production of reactive oxygen species, and invasive capacity after treatment of human dermal fibroblasts (HDF) and cells of the squamous tumor cell line (SCL-1) with Fe3O4 nanoparticles. These nanoparticles had an average size of 65 nm. Fe3O4 nanoparticles induced oxidative stress via generation of reactive oxygen species (ROS) and subsequent initiation of lipid peroxidation. Furthermore, the question was addressed of whether Fe3O4 nanoparticles affect myofibroblast formation, known to be involved in tumor invasion. Herein, Fe3O4 nanoparticles prevent the expression alpha-smooth muscle actin and therefore decrease the number of myofibroblastic cells. Moreover, our data show in vitro that concentrations of Fe3O4 nanoparticles, which are nontoxic for normal cells, partially reveal a ROS-triggered cytotoxic but also a pro-invasive effect on the fraction of squamous cancer cells surviving the treatment with Fe3O4 nanoparticles. The data herein show that the Fe3O4 nanoparticles appear not to be adequate for use in therapeutic approaches against cancer cells, in contrast to recently published data with cerium oxide nanoparticles. Lirija Alili, Swetlana Chapiro, Gernot U. Marten, Annette M. Schmidt, Klaus Zanger, and Peter Brenneisen Copyright © 2015 Lirija Alili et al. All rights reserved. The MicroRNA3686 Inhibits the Proliferation of Pancreas Carcinoma Cell Line by Targeting the Polo-Like Kinase 1 Thu, 21 May 2015 11:39:14 +0000 The Polo-like kinase 1 (PLK1) is one member of the so-called Polo-like kinase family which plays an important role in tumorigenesis. By analyzing the potential complementary microRNA (miRNA) targeting sequence of PLK1, we identified that miRNA-3686 (hereby and thereafter mir3696) could be the potential regulator for PLK1. Real-time PCR demonstrated that the mir3686 has a relatively higher expression in the immortalized pancreas cell HPDE6C7 than pancreas carcinoma derived cell line PANC1. The upregulation of mir3686 in HPDE6C7 cell corresponded with the low expression of PLK1 as well. Both luciferase based reporter assay and evaluation of endogenous PLK1 expression demonstrated that mir3686 regulated PLK1, which confirms our speculation. Moreover, we found that transfection of mir3686 in PANC1 cell could lead to proliferation inhibition and promote apoptosis. Further analysis demonstrated that mir3686 transfection in PANC1 cell also inhibited cell invasion, and clone formation in cell invasion assay and clonogenic cell survival assay, respectively. In contrast, inhibition of mir3686 expression in HPDE6C7 cell enhanced the capability of proliferation, cell invasion and clone formation. Taken together, our results indicated that mir3686 could target PLK1 to inhibit the cell proliferation in pancreas cancer derived cell line and mir3686 could be a new therapeutic target for pancreas cancer treatment. Hong-Yi Jin, Xin-Guang Qiu, and Bo Yang Copyright © 2015 Hong-Yi Jin et al. All rights reserved. In Vitro Antiproliferative Effect of the Acetone Extract of Rubus fairholmianus Gard. Root on Human Colorectal Cancer Cells Thu, 21 May 2015 11:30:27 +0000 Plants and plant derived products exert chemopreventive effects on various cancer cell lines by the induction of cell death mechanisms. The effects of root acetone extract of Rubus fairholmianus (RFRA) on the proliferation of human colorectal cancer (Caco-2) cells have been investigated in this study. The extract led to a dose dependent decrease in both viability and proliferation and increased cytotoxicity using trypan blue exclusion, adenosine 5′-triphosphate (ATP), and lactate dehydrogenase (LDH) assay. The morphological features of the treated cells were supportive for the antiproliferative activity. The Annexin V/propidium iodide staining indicated that R. fairholmianus induced toxic effects in Caco-2 cells and the percentages of the early and late apoptotic population significantly increased when compared with control cells. Also we studied the apoptosis inducing ability of the extract by analysing caspase 3/7 activity and the induction of cell death via the effector caspases was confirmed; the activity increased in treated cells compared with control. Thus the present findings highlight that the R. fairholmianus root acetone extract exhibits antiproliferative activity on Caco-2 cells by the induction of apoptosis via caspase dependent pathway. Blassan Plackal Adimuriyil George, Ivan Mfouo Tynga, and Heidi Abrahamse Copyright © 2015 Blassan Plackal Adimuriyil George et al. All rights reserved. Inflammatory Joint Diseases Thu, 21 May 2015 11:21:56 +0000 Guixiu Shi, Julian L. Ambrus, Shuang Ye, and Long Shen Copyright © 2015 Guixiu Shi et al. All rights reserved. Liver Failure Impairs the Intrahepatic Elimination of Interleukin-6, Tumor Necrosis Factor-Alpha, Hepatocyte Growth Factor, and Transforming Growth Factor-Beta Thu, 21 May 2015 11:20:27 +0000 The strategic location of the liver and its metabolic activity make it a key organ regulating homeostasis. Our purpose was to examine its participation in removal of cytokines: interleukin-6 (Il-6), tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor (HGF), and transforming growth factor-beta (TGF-β) from the portal circulation in human. 20 liver donors and 20 patients with end-stage liver failure were included in the study. Their blood was collected during liver transplantation from the portal, hepatic, and peripheral vein, and the hepatic artery and cytokines’ concentrations were determined. Using the results the mathematical model of cytokine elimination by the liver was developed. In donors significantly lower levels of IL-6, TNF-α, HGF, and TGF-β were detected in portal blood compared to hepatic vein. In patients with cirrhosis there were no significant differences of IL-6, TNF-α, and TGF-β levels between portal and hepatic veins. Significantly higher level of HGF in hepatic compared to portal vein was observed. In healthy liver elimination of the cytokines prevailed over their synthesis, as reflected by the positive values of the elimination ratios. In the cirrhotic liver elimination ratios of Il-6, HGF, and TGF-β were negative indicating the prevalence of intrahepatic synthesis of cytokines over their removal. Dawid Porowski, Agnieszka Wirkowska, Ewa Hryniewiecka, Janusz Wyzgał, Marek Pacholczyk, and Leszek Pączek Copyright © 2015 Dawid Porowski et al. All rights reserved. Mass Spectrometry Applications in Biomedical Research Thu, 21 May 2015 09:56:37 +0000 Fa-Yun Che, Hai-Teng Deng, and Shi-Jian Ding Copyright © 2015 Fa-Yun Che et al. All rights reserved. Mcl-1 Is a Novel Target of miR-26b That Is Associated with the Apoptosis Induced by TRAIL in HCC Cells Thu, 21 May 2015 08:50:14 +0000 Aim. To investigate the role of miR-26b and Mcl-1 in TRAIL-inducing cell death in hepatocellular carcinoma. Methods. The expression of miR-26b and Mcl-1 in HCC was detected by RT-qPCR and western blot. The regulation of Mcl-1 by miR-26b was determined by luciferase reporter assay. MTT and flow cytometry were employed to detect the cell viability and apoptosis. Results. miR-26b is commonly downregulated in HCC cell lines compared with the LO2 cell line. In contrast, the Mcl-1 expression is upregulated in HCC cell lines. Bioinformatic analysis identified a putative target site in the Mcl-1 mRNA for miR-26b and luciferase reporter assay showed that miR-26b directly targeted the 3′-UTR (3′-Untranslated Regions) of Mcl-1 mRNA. Transfection of miR-26b mimics suppressed Mcl-1 expression in HCC cells and sensitized the cancer cells to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) cytotoxicity. In addition, transfection of HCC cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-26b to TRAIL-inducing apoptosis. Conclusions. Our study showed that miR-26b was a negative regulator of Mcl-1 gene and sensitized TRAIL-inducing apoptosis in HCC cells, suggesting that the miR-26b-Mcl-1 pathway might be a novel target for the treatment of HCC. Chunlin Jiang, Jianting Long, Baoxian Liu, Xiaoyan Xie, and Ming Kuang Copyright © 2015 Chunlin Jiang et al. All rights reserved. Outbreak Control and Clinical, Pathological, and Epidemiological Aspects and Molecular Characterization of a Bovine Herpesvirus Type 5 on a Feedlot Farm in São Paulo State Thu, 21 May 2015 07:42:27 +0000 This paper describes the control, epidemiological, pathological, and molecular aspects of an outbreak of meningoencephalitis in calves due to bovine herpesvirus 5 at a feedlot with 540 animals in São Paulo State, Brazil. The introduction of new animals and contact between the resident animals and the introduced ones were most likely responsible for virus transmission. Bovine herpesvirus 1 vaccine was used, resulting in the efficacy of the outbreak control, although two bovine herpesvirus 1 positive animals, vaccinated and revaccinated, presented meningoencephalitis, thereby characterizing vaccinal failure. Jane Megid, Acácia Ferreira Vicente, Camila Michele Appolinario, Susan Dora Allendorf, Mateus de Souza Ribeiro Mioni, Thaís Gasparini Baraldi, Adriana Cortez, Marcos Bryan Heinemann, Clovis Reinaldo Silva Fonseca, Vanessa Cristina Pelícia, Bruna Leticia Devidé Ribeiro, Liria Hiromi Okuda, and Edviges Maristela Pituco Copyright © 2015 Jane Megid et al. All rights reserved. Role of B7-H4 siRNA in Proliferation, Migration, and Invasion of LOVO Colorectal Carcinoma Cell Line Thu, 21 May 2015 07:23:03 +0000 Objectives. Colorectal cancer is one of the most common malignancies. Recent studies investigated that B7-H4 is highly expressed in various cancers. We aimed at exploring the effect of B7-H4 siRNA on proliferation, invasion, and migration of LOVO cells which expressed B7-H4 notably. Design and Methods. Colon adenocarcinoma dataset was downloaded from The Cancer Genome Atlas. 35 colorectal cancer patients admitted to Shanghai Tongren Hospital were enrolled in this study. Cell proliferation and cell cycle distribution were identified by CCK8 and flow cytometry, respectively. Transwell assay was performed to detect the invasion and migration of LOVO cells. CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were determined by real-time PCR and western blot. Results. B7-H4 expressed is elevated in colorectal cancer tissues than in the adjacent normal tissues. B7-H4 siRNA effectively inhibited the proliferation at 24 h and 48 h, arrested cell cycle at G0/G1, and suppressed cell invasion and migration. Gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT were correlative with the B7-H4 expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced. Conclusions. B7-H4 siRNA can effectively inhibit proliferation, invasion, and migration of LOVO cells by targeting CXCL12/CXCR4 and JAK2/STAT3 signaling, which can serve as a new target for colorectal carcinoma treatment. Hai-xia Peng, Wei-qi Wu, Da-ming Yang, Rong Jing, Ji Li, Feng-li Zhou, Yun-fei Jin, Sai-yu Wang, and Yi-min Chu Copyright © 2015 Hai-xia Peng et al. All rights reserved. Signal Transduction Inhibitors as Promising Anticancer Agents Thu, 21 May 2015 07:15:36 +0000 Raj Kumar, Cedric Dos Santos, Tarunveer Singh Ahluwalia, and Sandeep Singh Copyright © 2015 Raj Kumar et al. All rights reserved. Helicobacter pylori Infection Thu, 21 May 2015 07:11:25 +0000 Ping-I Hsu, Yoshio Yamaoka, Khean-Lee Goh, Marco Manfredi, Deng-Chyang Wu, and Varocha Mahachai Copyright © 2015 Ping-I Hsu et al. All rights reserved. Toxicity of Nanomaterials Wed, 20 May 2015 14:14:38 +0000 Haseeb A. Khan and Rishi Shanker Copyright © 2015 Haseeb A. Khan and Rishi Shanker. All rights reserved. Human Genetic Diseases Wed, 20 May 2015 13:44:57 +0000 Hao Deng, Peter Riederer, Han-Xiang Deng, Weidong Le, Wei Xiong, and Yi Guo Copyright © 2015 Hao Deng et al. All rights reserved. Anticancer Properties of Natural Products Wed, 20 May 2015 13:37:37 +0000 István Zupkó, Walter Jaeger, Zeki Topcu, and Chin-Chung Wu Copyright © 2015 István Zupkó et al. All rights reserved. Advances in the Development of Biotherapeutics Wed, 20 May 2015 13:35:53 +0000 Pedro H. Oliveira, Juergen Mairhofer, Paula M. Alves, Alvaro R. Lara, and Cleo Kontoravdi Copyright © 2015 Pedro H. Oliveira et al. All rights reserved. Chewing, Stress-Related Diseases, and Brain Function Wed, 20 May 2015 13:35:13 +0000 Kin-ya Kubo, Huayue Chen, Xiaolin Zhou, Jian-Hua Liu, and Olivier Darbin Copyright © 2015 Kin-ya Kubo et al. All rights reserved. Sensitive Detection of Thirteen Bacterial Vaginosis-Associated Agents Using Multiplex Polymerase Chain Reaction Wed, 20 May 2015 11:29:10 +0000 Bacterial vaginosis (BV) is characterized by a polymicrobial proliferation of anaerobic bacteria and depletion of lactobacilli, which are components of natural vaginal microbiota. Currently, there are limited conventional methods for BV diagnosis, and these methods are time-consuming, expensive, and rarely allow for the detection of more than one agent simultaneously. Therefore, we conceived and validated a multiplex polymerase chain reaction (M-PCR) assay for the simultaneous screening of thirteen bacterial vaginosis-associated agents (BV-AAs) related to symptomatic BV: Gardnerella vaginalis, Mobiluncus curtisii, Mobiluncus mulieris, Bacteroides fragilis, Mycoplasma hominis, Atopobium vaginae, Ureaplasma urealyticum, Megasphaera type I, Clostridia-like bacteria vaginosis-associated bacteria (BVABs) 1, 2, and 3, Sneathia sanguinegens, and Mycoplasma genitalium. The overall validation parameters of M-PCR compared to single PCR (sPCR) were extremely high, including agreement of 99.1% and sensitivity, specificity, and positive predictive values of 100.0%, negative predictive value of 97.0%, accuracy of 99.3%, and agreement with Nugent results of 100.0%. The prevalence of BV-AAs was very high (72.6%), and simultaneous agents were detected in 53.0%, which demonstrates the effectiveness of the M-PCR assay. Therefore, the M-PCR assay has great potential to impact BV diagnostic methods in vaginal samples and diminish associated complications in the near future. Natália Malaguti, Larissa Danielle Bahls, Nelson Shozo Uchimura, Fabrícia Gimenes, and Marcia Edilaine Lopes Consolaro Copyright © 2015 Natália Malaguti et al. All rights reserved. Molecular Analysis of AFP and HSA Interactions with PTEN Protein Wed, 20 May 2015 11:24:17 +0000 Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA), but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP), and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog), demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma. Mingyue Zhu, Bo Lin, Peng Zhou, and Mengsen Li Copyright © 2015 Mingyue Zhu et al. All rights reserved. Changes in Heart Rate Variability after Coronary Artery Bypass Grafting and Clinical Importance of These Findings Wed, 20 May 2015 11:05:37 +0000 Heart rate variability is a physiological feature indicating the influence of the autonomic nervous system on the heart rate. Association of the reduced heart rate variability due to myocardial infarction and the increased postinfarction mortality was first described more than thirty years ago. Many studies have unequivocally demonstrated that coronary artery bypass grafting surgery generally leads to significant reduction in heart rate variability, which is even more pronounced than after myocardial infarction. Pathophysiologically, however, the mechanisms of heart rate variability reduction associated with acute myocardial infarction and coronary artery bypass grafting are different. Generally, heart rate variability gradually recovers to the preoperative values within six months of the procedure. Unlike the reduced heart rate variability in patients having sustained myocardial infarction, a finding of reduced heart rate variability after coronary artery bypass surgery is not considered relevant in predicting mortality. Current knowledge about changes in heart rate variability in coronary patients and clinical relevance of such a finding in patients undergoing coronary artery bypass grafting are presented. Nenad Lakusic, Darija Mahovic, Peter Kruzliak, Jasna Cerkez Habek, Miroslav Novak, and Dusko Cerovec Copyright © 2015 Nenad Lakusic et al. All rights reserved. Insights in Behavior of Variably Formulated Alginate-Based Microcapsules for Cell Transplantation Wed, 20 May 2015 10:00:35 +0000 Alginate-based microencapsulation of live cells may offer the opportunity to treat chronic and degenerative disorders. So far, a thorough assessment of physical-chemical behavior of alginate-based microbeads remains cloudy. A disputed issue is which divalent cation to choose for a high performing alginate gelling process. Having selected, in our system, high mannuronic (M) enriched alginates, we studied different gelling cations and their combinations to determine their eventual influence on physical-chemical properties of the final microcapsules preparation, in vitro and in vivo. We have shown that used of ultrapure alginate allows for high biocompatibility of the formed microcapsules, regardless of gelation agents, while use of different gelling cations is associated with corresponding variable effects on the capsules’ basic architecture, as originally reported in this work. However, only the final application which the capsules are destined to will ultimately guide the selection of the ideal, specific gelling divalent cations, since in principle there are no capsules that are better than others. Pia Montanucci, Silvia Terenzi, Claudio Santi, Ilaria Pennoni, Vittorio Bini, Teresa Pescara, Giuseppe Basta, and Riccardo Calafiore Copyright © 2015 Pia Montanucci et al. All rights reserved. Quantitative Assessment of the Association between Genetic Variants in MicroRNAs and Colorectal Cancer Risk Wed, 20 May 2015 09:31:47 +0000 Background. The associations between polymorphisms in microRNAs and the susceptibility of colorectal cancer (CRC) were inconsistent in previous studies. This study aims to quantify the strength of the correlation between the four common polymorphisms among microRNAs (hsa-mir-146a rs2910164, hsa-mir-149 rs2292832, hsa-mir-196a2 rs11614913, and hsa-mir-499 rs3746444) and CRC risk. Methods. We searched PubMed, Web of Knowledge, and CNKI to find relevant studies. The combined odds ratio (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the association in a fixed or random effect model. Results. 15 studies involving 5,486 CRC patients and 7,184 controls were included. Meta-analyses showed that rs3746444 had association with CRC risk in Caucasians (OR = 0.57, 95% CI = 0.34–0.95). In the subgroup analysis, we found significant associations between rs2910164 and CRC in hospital based studies (OR = 1.24, 95% CI = 1.03–1.49). rs2292832 may be a high risk factor of CRC in population based studied (OR = 1.18, 95% CI = 1.08–1.38). Conclusion. This meta-analysis showed that rs2910164 and rs2292832 may increase the risk of CRC. However, rs11614913 polymorphism may reduce the risk of CRC. rs3746444 may have a decreased risk to CRC in Caucasians. Xiao-Xu Liu, Meng Wang, Dan Xu, Jian-Hai Yang, Hua-Feng Kang, Xi-Jing Wang, Shuai Lin, Peng-Tao Yang, Xing-Han Liu, and Zhi-Jun Dai Copyright © 2015 Xiao-Xu Liu et al. All rights reserved. Target-Specific Oral Anticoagulants—New Approaches in the Field of Oral Anticoagulation Wed, 20 May 2015 09:03:09 +0000 Helen Mani, Jonathan Douxfils, and Jack Ansell Copyright © 2015 Helen Mani et al. All rights reserved.