BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Association between Two Common Polymorphisms and Risk of Hepatocellular Carcinoma: Evidence from an Updated Meta-Analysis Thu, 17 Apr 2014 16:55:31 +0000 Background. Recent studies suggested that two common polymorphisms, miR-146a G>C and miR-196a2 C>T, may be associated with individual susceptibility to hepatocellular carcinoma (HCC). However, the results remain conflicting rather than conclusive. Object. The aim of this study was to assess the association between miR-146a G>C and miR-196a2 C>T polymorphisms and the risk of HCC. Methods. A meta-analysis of 17 studies (10938 cases and 11967 controls) was performed. Odds ratios and 95% confidence intervals were used to evaluate the strength of the association. Results. For miR-146a G>C, the variant genotypes were associated with a decreased risk of HCC (CC versus GG: OR = 0.780 and 95% CI 0.700–0.869; GC/CC versus GG: OR = 0.865 and 95% CI 0.787–0.952; CC versus GC/GG: OR = 0.835 and 95% CI 0.774–0.901). For miR-196a2 C>T, significant association was also observed (TT versus CC: OR = 0.783, 95% CI: 0.649–0.943, and ; CT versus CC: OR = 0.831, 95% CI 0.714–0.967, and ; CT/TT versus CC: OR = 0.817, 95% CI 0.703–0.949, and ). Conclusion. The two common polymorphisms miR-146a G>C and miR-196a2 C>T were associated with decreased HCC susceptibility, especially in Asian population. Zhaoming Wang, Lei Zhang, Xuesong Shi, Huayu Xu, Ting Wang, and Jianmin Bian Copyright © 2014 Zhaoming Wang et al. All rights reserved. Combinatorial Control of Transgene Expression by Hypoxia-Responsive Promoter and MicroRNA Regulation for Neural Stem Cell-Based Cancer Therapy Thu, 17 Apr 2014 14:11:28 +0000 Owing to their strong migratory capacity, tumor tropism, and tumor inhibitory effect, neural stem cells (NSCs) have recently emerged as one of the most attractive gene delivery vectors for cancer therapy. However, further animal studies found that proportional NSC vectors were distributed to nontarget organs after intravenous injection and the nonspecific transgene expression led to significant cytotoxic effects in these organs. Hence, an expression cassette that controls the transgene expression within NSC vectors in a tumor site-specific manner is desired. Considering hypoxia as a hallmark of tumor microenvironment, we have developed a novel NSC vector platform coupling transcriptional targeting with microRNA (miRNA) regulation for tumor hypoxia targeting. This combinatorial vector employed a hypoxia-responsive promoter and repeated targeting sequences of an miRNA that is enriched in NSCs but downregulated upon hypoxia induction to control the transgene expression. This resulted in significantly improved hypoxic selectivity over the use of a control vector without miRNA regulation. Thus, incorporating miRNA regulation into a transcriptional targeting vector adds an extra layer of security to prevent off-target transgene expression and should be useful for the development of NSC vectors with high targeting specifcity for cancer therapy. Yumei Luo and Detu Zhu Copyright © 2014 Yumei Luo and Detu Zhu. All rights reserved. Macrophage Plasticity in Skeletal Muscle Repair Thu, 17 Apr 2014 14:04:02 +0000 Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle. Elena Rigamonti, Paola Zordan, Clara Sciorati, Patrizia Rovere-Querini, and Silvia Brunelli Copyright © 2014 Elena Rigamonti et al. All rights reserved. Epithelial-Mesenchymal Transition Regulated by EphA2 Contributes to Vasculogenic Mimicry Formation of Head and Neck Squamous Cell Carcinoma Thu, 17 Apr 2014 13:34:19 +0000 Purpose. Vasculogenic mimicry (VM) was related to invasion and metastasis of head and neck squamous cell carcinoma (HNSCC) patients. This study was designed to investigate the role of EphA2 in VM formation of HNSCC. Methods. The SiRNA technique was used to knock down the expression of EphA2 in vitro. The ability of cell migration and invasion were measured by transwell and wound healing assays; three-dimensional culture was used to detect the ability of channel-like structure formation; Western blot was used to detect the expression of epithelial-mesenchymal transition- (EMT-) related molecules in vitro. Further semiquantitative real-time RT-PCR assays and immunohistochemistry were used to demonstrate expression of EphA2 and EMT-related molecules according to VM presence or not in human tissue. Results. Knocking down EphA2 in vitro leads to disabled channel-like structure formation, reduction of invasion and migration ability, and reverse of EMT-related markers. Both semiquantitative real-time RT-PCR and immunohistochemistry showed that expressions of EphA2, Twist, and Vimentin were higher in the VM-positive group than in the VM-negative group significantly, while expressions of E-cadherin, claudin4, and DSG-3 were reverse. Conclusions. EphA2 played a key role in VM formation of HNSCC through regulation of EMT. Wei Wang, Peng Lin, Baocun Sun, Shiwu Zhang, Wenjuan Cai, Chunrong Han, Li Li, Honghua Lu, and Xiulan Zhao Copyright © 2014 Wei Wang et al. All rights reserved. Serial Serum Leukocyte Apoptosis Levels as Predictors of Outcome in Acute Traumatic Brain Injury Thu, 17 Apr 2014 13:33:18 +0000 Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI). This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome. Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects. Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (), motor deficits (), GCS (), ISS (), WBC count (), late apoptosis in lymphocytes and monocytes on Day 1 ( and , resp.), subdural hemorrhage on initial brain CT (), neurosurgical intervention (), and acute posttraumatic seizure () were significant risk factors of outcome. Only motor deficits () and late apoptosis in monocytes on Day 1 () were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients. Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury. Hung-Chen Wang, Tzu-Ming Yang, Yu-Jun Lin, Wu-Fu Chen, Jih-Tsun Ho, Yu-Tsai Lin, Aij-Lie Kwan, and Cheng-Hsien Lu Copyright © 2014 Hung-Chen Wang et al. All rights reserved. Does Long-Term Use of Silver Nanoparticles Have Persistent Inhibitory Effect on H. pylori Based on Mongolian Gerbil’s Model? Thu, 17 Apr 2014 13:32:32 +0000 Background. It is urgent to find alternative agents due to increasing failure rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long-term effect of silver nanoparticles (AgNP) on H. pylori based on Mongolian gerbil’s model. Materials and Methods. Fifty gerbils were randomly allocated to six groups (A–F). Group (Gr) A: the gerbils were fed with broth; Gr B and D: the gerbils were fed with AgNP/clay complex (0.1% of weight); Gr C and E: the gerbils were fed with AgNP/clay complex(1% of weight); and Gr D, E, and F: the gerbils were inoculated with H. pylori. At the 20th experimental week, the gerbils were sacrificed. Histology was evaluated according to the classification of the Sydney system. was considered to be statistically significant. Results. The AgNP/clay has more obvious inhibitory effect on H. pylori in vitro. There was a trend of higher concentrations of AgNP with stronger inhibitory effect on H. pylori growth . There were no significant differences of inflammation among groups D, E, and F Conclusion. AgNP/clay would be a potential and safe agent for inhibiting H. pylori. It should be helpful for eradication of H. pylori infection. Chao-Hung Kuo, Chien-Yu Lu, Yuan-Chieh Yang, Chieh Chin, Bi-Chuang Weng, Chung-Jung Liu, Yen-Hsu Chen, Lin-Li Chang, Fu-Chen Kuo, Deng-Chyang Wu, and Hong-Lin Su Copyright © 2014 Chao-Hung Kuo et al. All rights reserved. Effect of Dietary Intake of Avocado Oil and Olive Oil on Biochemical Markers of Liver Function in Sucrose-Fed Rats Thu, 17 Apr 2014 13:32:31 +0000 Metabolic changes, along with cardiovascular and hepatic factors, are associated with the development of diseases such as diabetes, dyslipidemia, and obesity. We evaluated the effect of avocado oil supplementation (centrifuged and solvent extracted), compared with olive oil, upon the hepatic function in sucrose-fed rats. Twenty-five rats were divided into five groups: control (basal diet), a sucrose-fed group (basal diet plus 30% sucrose solution), and three other groups (S-OO, S-AOC, and S-AOS, indicating basal diet plus 30% sucrose solution plus olive oil OO, avocado oil extracted by centrifugation AOC or using solvent AOS, resp.). Glucose, total cholesterol, triglycerides, total protein, albumin, globulin, direct bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, cholinesterase, and α-amylase concentrations were determined and avocado oil effect on them was studied. In some cases the induced metabolic alteration significantly affected total protein and bilirubin levels and also had a highly significant effect on α-amylase levels. AOC and AOS exhibited effects similar to those of olive oil, according to the nonsignificant difference in fatty acid profile observed by other authors. Avocado oil consumption could be beneficial in the control of altered metabolic profile illnesses as it presents effects on hepatic function biochemical markers similar to olive oil. Octavio Carvajal-Zarrabal, Cirilo Nolasco-Hipolito, Ma. Guadalupe Aguilar-Uscanga, Guadalupe Melo Santiesteban, Patricia M. Hayward-Jones, and Dulce Ma. Barradas-Dermitz Copyright © 2014 Octavio Carvajal-Zarrabal et al. All rights reserved. Neuroimaging to Investigate Multisystem Involvement and Provide Biomarkers in Amyotrophic Lateral Sclerosis Thu, 17 Apr 2014 13:29:05 +0000 Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS). Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS. Pierre-François Pradat and Mohamed-Mounir El Mendili Copyright © 2014 Pierre-François Pradat and Mohamed-Mounir El Mendili. All rights reserved. Cerebral Endothelial Function Determined by Cerebrovascular Reactivity to L-Arginine Thu, 17 Apr 2014 12:41:27 +0000 Endothelium forms the inner cellular lining of blood vessels and plays an important role in many physiological functions including the control of vasomotor tone. Cerebral endothelium is probably one of the most specific types but until recently it was impossible to determine its function. In this review, the role of cerebrovascular reactivity to L-arginine (CVR-L-Arg) for assessment of cerebral endothelial function is discussed. L-Arginine induces vasodilatation through enhanced production of nitric oxide (NO) in the cerebral endothelium. Transcranial Doppler sonography is used for evaluation of cerebral blood flow changes. The method is noninvasive, inexpensive, and enables reproducible measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold standard for systemic endothelial function and intima-media thickness as a marker for morphological changes. However, it seems to show specific cerebral endothelial function. So far CVR-L-Arg has been used to study cerebral endothelial function in many pathological conditions such as stroke, migraine, etc. In addition CVR-L-Arg has also proven its usefulness in order to show potential improvement after pharmacological interventions. In conclusion CVR-L-Arg is a promising noninvasive research method that could provide means for evaluation of cerebral endothelial function in physiological and pathological conditions. Janja Pretnar-Oblak Copyright © 2014 Janja Pretnar-Oblak. All rights reserved. Association between Risk Factors for Vascular Dementia and Adiponectin Thu, 17 Apr 2014 12:22:25 +0000 Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia. Juhyun Song, Won Taek Lee, Kyung Ah Park, and Jong Eun Lee Copyright © 2014 Juhyun Song et al. All rights reserved. Building and Repairing the Heart: What Can We Learn from Embryonic Development? Thu, 17 Apr 2014 11:03:39 +0000 Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed. Ana G. Freire, Tatiana P. Resende, and Perpétua Pinto-do-Ó Copyright © 2014 Ana G. Freire et al. All rights reserved. Effect of Curcumin on Lifespan, Activity Pattern, Oxidative Stress, and Apoptosis in the Brains of Transgenic Drosophila Model of Parkinson’s Disease Thu, 17 Apr 2014 10:19:53 +0000 Background. A time dependent loss of dopaminergic neurons and the formation of intracellular aggregates of alpha synuclein have been reported in PD model flies. Methods. The progeny (PD flies) expressing human alpha synuclein was exposed to 25, 50, and 100 µM of curcumin mixed in the diet for 24 days. The effect of curcumin was studied on lifespan, activity pattern, oxidative stress, and apoptosis in the brains of PD model flies. The activity of PD model flies was monitored by using Drosophila activity monitors (DAMs). For the estimation of oxidative stress, lipid peroxidation and protein carbonyl content were estimated in the flies brains of each treated groups. The cell death in Drosophila brain was analyzed by isolating brains in Ringer’s solution placing them in 70% ethanol and stained in acridine orange to calculate the gray scale values. Results. The exposure of flies to 25, 50, and 100 µM of curcumin showed a dose dependent significant delay in the loss of activity pattern, reduction in the oxidative stress and apoptosis, and increase in the life span of PD model flies. Conclusion. Curcumin is potent in reducing PD symptoms. Yasir Hasan Siddique, Falaq Naz, and Smita Jyoti Copyright © 2014 Yasir Hasan Siddique et al. All rights reserved. Coastal Biotechnology: Facing the Global and the Regional Changes Thu, 17 Apr 2014 10:05:48 +0000 Song Qin, Wei Zhang, and Hanzhi Lin Copyright © 2014 Song Qin et al. All rights reserved. In Search of the Active Metabolites of an Anticancer Piperazinedione, TW01003, in Rats Thu, 17 Apr 2014 10:05:12 +0000 TW01003, a piperazinedione derivative designed as an antimitotic agent, exhibited potent anticancer and antiangiogenesis activities in mice. However, oral administration of this compound in rats led to poor systemic bioavailability which suggested that in vivo efficacy might come from its metabolites. This report describes the identification of TW01003 metabolites in pig and Wistar rats. Following intravenous administration of TW01003, pig urine samples were subjected to sulfatase and glucuronidase treatment to monitor the biotransformation products. Rats were given TW01003 both intravenously and orally, and blood samples were collected and then analyzed by HPLC to quantitatively determine the metabolic transformation of TW01003 to its metabolite. A sulfate conjugate, TW01003 sulfate, was identified as the major metabolite for TW01003 after intravenous injection in both pig and rats. However, in rats, the glucuronide conjugate became major metabolite 30 min after TW01003 oral dosing. Pharmacokinetic analysis after intravenous administration of TW01003 indicated that TW01003 sulfate had a systemic bioavailability 2.5 times higher, volume of distribution three times higher, residence time seven times longer, and clearance rate 2.3 times lower compared to TW01003. Our results indicate that the potent anticancer and antiangiogenesis activities of TW01003 might not come from TW01003 per se but from its metabolites TW01003 sulfate. Chun-Li Wang, Ching-Kuei Chen, Yao-Horng Wang, and Yu-Wen Cheng Copyright © 2014 Chun-Li Wang et al. All rights reserved. Tissue Biomarkers in Prognostication of Serous Ovarian Cancer following Neoadjuvant Chemotherapy Thu, 17 Apr 2014 10:04:19 +0000 Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients () that were treated either conventionally () or with NACT (), followed by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1, estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2), immunohistochemistry and semiquantitative scoring were done following morphological examination. Following NACT, significant differences in tumor histomorphology were observed as compared to the native neoplasms. MIB 1 was significantly lower in cases treated with NACT and survival outcome was significantly better in cases with low MIB 1. ER expression was associated with poor overall survival. No other marker displayed any significant difference in expression or correlation with survival between the two groups. Immunophenotype of SOC does not differ significantly in samples from cases treated with NACT, compared to upfront surgically treated cases. The proliferating capacity of the residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER inversely correlate with survival. Binny Khandakar, Sandeep R. Mathur, Lalit Kumar, Sunesh Kumar, Siddhartha Datta Gupta, Venkateswaran K. Iyer, and M. Kalaivani Copyright © 2014 Binny Khandakar et al. All rights reserved. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment Thu, 17 Apr 2014 09:42:54 +0000 Objective. Layered double hydroxide (LDH) nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML), 5-FU/LDH (FL), and (MTX + 5-FU)/LDH (MFL) nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy. Tae-Hyun Kim, Gyeong Jin Lee, Joo-Hee Kang, Hyoung-Jun Kim, Tae-il Kim, and Jae-Min Oh Copyright © 2014 Tae-Hyun Kim et al. All rights reserved. Biodegradation and Utilization of Organophosphorus Pesticide Malathion by Cyanobacteria Thu, 17 Apr 2014 08:48:18 +0000 Three strains of filamentous Cyanobacteria were used to study their growth and utilization of organophosphorus pesticide malathion. A sharp decrease in the growth of the algal strains was observed by increasing the concentration of malathion. Amongst them Nostoc muscorum tolerated different concentrations and was recorded as the highest efficient strain for biodegradation (91%) of this compound. Moreover, carbohydrate and protein content of their cells overtopped the other strains especially at higher concentrations. The algal strains were further subjected to grow under P-limitation in absence and presence of malathion. Although, the algal growth under P-limitation recorded a very poor level, a massive enhanced growth and phosphorous content of cells were obtained when the P-limited medium was amended with malathion. This study clarified that N. muscorum with its capability to utilize malathion as a sole phosphorous source is considered as an inexpensive and efficient biotechnology for remediation of organophosphorus pesticide from contaminated wastewater. Wael M. Ibrahim, Mohamed A. Karam, Reda M. El-Shahat, and Asmaa A. Adway Copyright © 2014 Wael M. Ibrahim et al. All rights reserved. Hyperglycemia, a Neglected Factor during Cancer Progression Thu, 17 Apr 2014 07:50:39 +0000 Recent evidence from large cohort studies suggests that there exists a higher cancer incidence in people with type 2 diabetes (DM2). However, to date, the potential reasons for this association remain unclear. Hyperglycemia, the most important feature of diabetes, may be responsible for the excess glucose supply for these glucose-hungry cells, and it contributes to apoptosis resistance, oncogenesis, and tumor cell resistance to chemotherapy. Considering associations between diabetes and malignancies, the effect of hyperglycemia on cancer progression in cancer patients with abnormal blood glucose should not be neglected. In this paper, we describe the role that hyperglycemia plays in cancer progression and treatment and illustrate that hyperglycemia may contribute to a more malignant phenotype of cancer cells and lead to drug resistance. Therefore, controlling hyperglycemia may have important therapeutic implications in cancer patients. Wanxing Duan, Xin Shen, Jianjun Lei, Qinhong Xu, Yongtian Yu, Rong Li, Erxi Wu, and Qingyong Ma Copyright © 2014 Wanxing Duan et al. All rights reserved. The Multiple Silicone Tube Device, “Tubes within a Tube,” for Multiplication in Nerve Reconstruction Thu, 17 Apr 2014 07:05:51 +0000 Multiple nerve branches were created during the regeneration procedure after a nerve injury and such multiple branches are suggested to be used to control, for example, prosthesis with many degrees of freedom. Transected rat sciatic nerve stumps were inserted into a nine mm long silicone tube, which contained four, five mm long, smaller tubes, thus leaving a five mm gap for regenerating nerve fibers. Six weeks later, several new nerve structures were formed not only in the four smaller tubes, but also in the spaces in-between. The 7–9 new continuous nerve structures, which were isolated as individual free nerves after removal of the tubes, were delineated by a perineurium and contained both myelinated and unmyelinated nerve fibers as well as blood vessels. Stimulation of the proximal nerve elicited contractions in distal muscles. Thin metal electrodes, inserted initially into the smaller tubes in some experiments, became embedded in the new nerve structures and when stimulated contractions of the distal muscles were observed. The “tubes within a tube” technique, creating multiple new nerves from a single “mother” nerve, can be used to record multiple signals for prosthetic device control or as sources for supply of multiple denervated targets. Fredrik Johansson and Lars B. Dahlin Copyright © 2014 Fredrik Johansson and Lars B. Dahlin. All rights reserved. Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study Thu, 17 Apr 2014 06:31:39 +0000 Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk factors for hypertension with inconsistent results, possibly due to heterogeneity among various genetic and environmental factors. A case-control association study was conducted to investigate a possible involvement of polymorphisms of three RAS genes: AGT M235T (rs699), ACE I/D (rs4340) and G2350A (rs4343), and AGTR1 A1166C (rs5186) in essential hypertensive patients. A total of 211 cases and 211 controls were recruited for this study. Genotyping was performed using PCR-RFLP method. The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (OR-CI = 2.62 (1.24–5.76), ; OR-CI = 0.699 (0.518–0.943), ), respectively. When the samples were segregated based on sex, the 235TT genotype and T allele were predominant in the female patients (OR-CI = 5.68 (1.60-25.10), ; OR-CI = 0.522 (0.330–0.826), ) as compare to the male patients (OR-CI = 1.54 (1.24–5.76), ; OR-CI = 0.874 (0.330–0.826), ), respectively. For ACE DD variant, we found overrepresentation of “I”-allele (homozygous II and heterozygous ID) in unaffected males which suggest its protective role in studied population (OR-CI = 0.401 (0.224–0.718); ). The M235T variant of the AGT is significantly associated with female hypertensives and ACE DD variant could be a risk allele for essential hypertension in south India. Kh. Dhanachandra Singh, Ajay Jajodia, Harpreet Kaur, Ritushree Kukreti, and Muthusamy Karthikeyan Copyright © 2014 Kh. Dhanachandra Singh et al. All rights reserved. Genetics of Type 2 Diabetes: Insights into the Pathogenesis and Its Clinical Application Thu, 17 Apr 2014 06:30:37 +0000 With rapidly increasing prevalence, diabetes has become one of the major causes of mortality worldwide. According to the latest studies, genetic information makes substantial contributions towards the prediction of diabetes risk and individualized antidiabetic treatment. To date, approximately 70 susceptibility genes have been identified as being associated with type 2 diabetes (T2D) at a genome-wide significant level (). However, all the genetic loci identified so far account for only about 10% of the overall heritability of T2D. In addition, how these novel susceptibility loci correlate with the pathophysiology of the disease remains largely unknown. This review covers the major genetic studies on the risk of T2D based on ethnicity and briefly discusses the potential mechanisms and clinical utility of the genetic information underlying T2D. Xue Sun, Weihui Yu, and Cheng Hu Copyright © 2014 Xue Sun et al. All rights reserved. The Impact of Hyperglycemia on Risk of Severe Infections during Early Period of Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma Wed, 16 Apr 2014 16:46:34 +0000 The association between hyperglycemia and infections during induction chemotherapy has been reported in a number of hematologic disorders. This retrospective study evaluated the incidence of hyperglycemia during induction therapy in 155 patients with newly diagnosed multiple myeloma (MM) and its effect on serious infections during the first 60 days of induction. A total of 20 (12.9%) patients developed overt hyperglycemia (≥200 mg/dL) during induction therapy. Serious infections occurred in 28 (18.1%) of 155 patients and infection-related mortality within 2 months after treatment was 0.6% (1 patient). In a univariate analysis, overt hyperglycemia, poor performance status (≥2), International Staging System III, lymphopenia (<500/μL), and elevated serum creatinine (≥2 mg/dL) were found to be associated with serious infections. In multivariate analysis, only overt hyperglycemia (HR 7.846, 95% CI 2.512–24.503, ) and poor performance status (HR 5.801, 95% CI 1.974–17.050, ) remained significant. In conclusion, this study demonstrated an association between hyperglycemia and serious infections during induction therapy in patients with MM. Sung-Hoon Jung, Hee-Chang Jang, Seung-Shin Lee, Jae-Sook Ahn, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, and Je-Jung Lee Copyright © 2014 Sung-Hoon Jung et al. All rights reserved. Role of 99mTc-ECD SPECT in the Management of Children with Craniosynostosis Wed, 16 Apr 2014 16:45:59 +0000 Purpose of the Report. There is a paucity of data on correlation of various imaging modalities with clinical findings in craniosynostosis. Moreover, no study has specifically reported the role of -ECD SPECT in a large number of subjects with craniosynostosis. Materials and Methods. We prospectively analyzed a cohort of 85 patients with craniosynostosis from year 2007 to 2012. All patients underwent evaluation with -ECD SPECT and the results were correlated with radiological and surgical findings. Results. -ECD SPECT revealed regional perfusion abnormalities in the cerebral hemisphere corresponding to the fused sutures preoperatively that disappeared postoperatively in all the cases. Corresponding to this, the mean mental performance quotient (MPQ) increased significantly postoperatively only in those children with absent perfusion defect postoperatively. Conclusions. Our study suggests that early surgery and release of craniosynostosis in patients with preoperative perfusion defects (absent on -ECD SPECT study) are beneficial, as theylead to improved MPQ after surgery. Mayadhar Barik, Minu Bajpai, Rashmi Ranajn Das, Arun Malhotra, Shasanka Shekhar Panda, Manas Kumar Sahoo, and Sadanand Dwivedi Copyright © 2014 Mayadhar Barik et al. All rights reserved. Surface Characteristics and Bioactivity of a Novel Natural HA/Zircon Nanocomposite Coated on Dental Implants Wed, 16 Apr 2014 16:45:25 +0000 The surface characteristics of implant which influence the speed and strength of osseointegration include surface chemistry, crystal structure and crystallinity, roughness, strain hardening, and presence of impurities. The aim of this study was to evaluate the bioactivity and roughness of a novel natural hydroxyapatite/zircon (NHA/zircon) nanobiocomposite, coated on 316L stainless steel (SS) soaked in simulated body fluid (SBF). NHA/zircon nanobiocomposite was fabricated with 0 wt.%, 5 wt.%, 10 wt.%, and 15 wt.% of zircon in NHA using ball mill for 20 minutes. The composite mixture was coated on 316L SS using plasma spray method. The results are estimated using the scanning electron microscopy (SEM) observation to evaluate surface morphology, X-ray diffraction (XRD) to analyze phase composition, and transmission electron microscopy (TEM) technique to evaluate the shape and size of prepared NHA. Surfaces roughness tester was performed to characterize the coated nanocomposite samples. The maximum average (14.54 μm) was found in the NHA 10 wt.% of zircon coating. In addition, crystallinity () was measured by XRD data, which indicated the minimum value ( = 41.1%) for the sample containing 10 wt.% of zircon. Maximum bioactivity occurred in the sample containing 10 wt.% of zircon, which was due to two reasons: first, the maximum roughness and, second, the minimum crystallinity of nanobiocomposite coating. Ebrahim Karamian, Amirsalar Khandan, Mahmood Reza Kalantar Motamedi, and Hesam Mirmohammadi Copyright © 2014 Ebrahim Karamian et al. All rights reserved. Two-Dimensional PCA Highlights the Differentiated Antitumor and Antimicrobial Activity of Methanolic and Aqueous Extracts of Laurus nobilis L. from Different Origins Wed, 16 Apr 2014 16:06:46 +0000 Natural matrices are important sources of new antitumor and antimicrobial compounds. Species such as Laurus nobilis L. (laurel) might be used for this purpose, considering its medicinal properties. Herein, in vitro activity against human tumor cell lines, bacteria, and fungi was evaluated in enriched phenolic extracts. Specifically, methanol and aqueous extracts of wild and cultivated samples of L. nobilis were compared considering different phenolic groups. Principal component analysis (PCA) was applied to understand how each extract acts differentially against specific bacteria, fungi, and selected human tumor cell lines. In general, the extract type induced the highest differences in bioactivity of laurel samples. However, from the PCA biplot, it became clear that wild laurel samples were higher inhibitors of tumor cell lines (HeLa, MCF7, NCI-H460, and HCT15). HepG2 had the same response to laurel from wild and cultivated origin. It was also observed that methanolic extracts tended to have higher antimicrobial activity, except against A. niger, A. fumigatus, and P. verrucosum. The differences in bioactivity might be related to the higher phenolic contents in methanolic extracts. These results allow selecting the extract type and/or origin with highest antibacterial, antifungal, and antitumor activity. Maria Inês Dias, João C. M. Barreira, Ricardo C. Calhelha, Maria-João R. P. Queiroz, M. Beatriz P. P. Oliveira, Marina Soković, and Isabel C. F. R. Ferreira Copyright © 2014 Maria Inês Dias et al. All rights reserved. Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis Wed, 16 Apr 2014 15:58:08 +0000 Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-κB and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis. Keliang Xie, Lingling Liu, Yonghao Yu, and Guolin Wang Copyright © 2014 Keliang Xie et al. All rights reserved. The Emerging Role of Biotechnological Drugs in the Treatment of Gout Wed, 16 Apr 2014 15:55:21 +0000 One of the most important therapeutic advances obtained in the field of rheumatology is the availability of the so-called bio(techno)logical drugs, which have deeply changed treatment perspectives in diseases such as rheumatoid arthritis and ankylosing spondylitis. According to the steadily increasing attention on gout, due to well-established prognostic and epidemiology implications, in the last 5 years, the same change of perspective has been observed also for this disease. In fact, several bio(techno)logical agents have been investigated both for the management of the articular gout symptoms, targeting mainly interleukin-1β, as well as urate-lowering therapies such as recombinant uricases. Among the IL-1β inhibitors, the majority of studies involve drugs such as anakinra, canakinumab, and rilonacept, but other compounds are under development. Moreover, other potential targets have been suggested, as, for example, the TNF alpha and IL-6, even if data obtained are less robust than those of IL-1β inhibitors. Regarding urate-lowering therapies, the recombinant uricases pegloticase and rasburicase clearly showed their effectiveness in gout patients. Also in this case, new compounds are under development. The aim of this review is to focus on the various aspects of different bio(techno)logical drugs in gouty patients. L. Cavagna and W. J. Taylor Copyright © 2014 L. Cavagna and W. J. Taylor. All rights reserved. Detection of Herpes Simplex and Varicella-Zoster Virus in Clinical Specimens by Multiplex Real-Time PCR and Melting Curve Analysis Wed, 16 Apr 2014 15:54:38 +0000 Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), and varicella-zoster virus (VZV) are common agents resulting in various forms of clinical manifestation from skin vesicle to disseminated viral infection. The aim of the present study was to develop a real-time PCR and melting curve analysis which detect and differentiate HSV-1, HSV-2, and VZV, to compare with PCR-RFLP using clinical specimens, and to introduce the 4-year experience in the clinical laboratory. Three pairs of primers for HSV-1, HSV-2, and VZV were designed. Primers for human endogenous retrovirus-3 (HERV-3), an internal control, were adopted. A hundred selected specimens and many clinical specimens were tested for methods comparison and assay validation. Increased sensitivity and specificity were obtained from real-time PCR. In review of results of clinical specimens submitted to clinical laboratory, a total of 46 of 3,513 specimens were positive in cerebrospinal fluids, blood, skin vesicles, genital swabs, aqueous humor, and ear discharge. Thus, this method could be a rapid and accurate alternative to virus culture and other molecular tests for detection and typing of HSV-1, HSV-2, and VZV. Yun Ji Hong, Mi Suk Lim, Sang Mee Hwang, Taek Soo Kim, Kyoung Un Park, Junghan Song, and Eui Chong Kim Copyright © 2014 Yun Ji Hong et al. All rights reserved. Using the Sadakane Compressed Suffix Tree to Solve the All-Pairs Suffix-Prefix Problem Wed, 16 Apr 2014 15:52:01 +0000 The all-pairs suffix-prefix matching problem is a basic problem in string processing. It has an application in the de novo genome assembly task, which is one of the major bioinformatics problems. Due to the large size of the input data, it is crucial to use fast and space efficient solutions. In this paper, we present a space-economical solution to this problem using the generalized Sadakane compressed suffix tree. Furthermore, we present a parallel algorithm to provide more speed for shared memory computers. Our sequential and parallel algorithms are optimized by exploiting features of the Sadakane compressed index data structure. Experimental results show that our solution based on the Sadakane’s compressed index consumes significantly less space than the ones based on noncompressed data structures like the suffix tree and the enhanced suffix array. Our experimental results show that our parallel algorithm is efficient and scales well with increasing number of processors. Maan Haj Rachid, Qutaibah Malluhi, and Mohamed Abouelhoda Copyright © 2014 Maan Haj Rachid et al. All rights reserved. A Knowledge-Driven Approach to Extract Disease-Related Biomarkers from the Literature Wed, 16 Apr 2014 15:51:54 +0000 The biomedical literature represents a rich source of biomarker information. However, both the size of literature databases and their lack of standardization hamper the automatic exploitation of the information contained in these resources. Text mining approaches have proven to be useful for the exploitation of information contained in the scientific publications. Here, we show that a knowledge-driven text mining approach can exploit a large literature database to extract a dataset of biomarkers related to diseases covering all therapeutic areas. Our methodology takes advantage of the annotation of MEDLINE publications pertaining to biomarkers with MeSH terms, narrowing the search to specific publications and, therefore, minimizing the false positive ratio. It is based on a dictionary-based named entity recognition system and a relation extraction module. The application of this methodology resulted in the identification of 131,012 disease-biomarker associations between 2,803 genes and 2,751 diseases, and represents a valuable knowledge base for those interested in disease-related biomarkers. Additionally, we present a bibliometric analysis of the journals reporting biomarker related information during the last 40 years. À. Bravo, M. Cases, N. Queralt-Rosinach, F. Sanz, and L. I. Furlong Copyright © 2014 À. Bravo et al. All rights reserved.