BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Constitutive NF-κB Activation Underlines Major Mechanism of Drug Resistance in Relapsed Refractory Diffuse Large B Cell Lymphoma Thu, 23 Apr 2015 14:32:04 +0000 Diffuse large B cell lymphoma (DLBCL) is the most common subtype of B cell non-Hodgkin’s lymphoma (NHL), encompassing 30–40% of the estimated 70,000 cases of NHL in 2014 in the USA. Despite major improvements with immune-chemotherapy, the fraction of patients who still succumb to a refractory or relapsed disease remains high. This review addresses whether the better understanding of the biology of DLBCL defines new therapeutic avenues that may overcome the emerging resistance of this disease to traditional immune-chemotherapy, such as rituximab in combination with traditional chemotherapy agents. Emerging targeted therapy for relapsed refractory DLBCL encompasses more complex molecular abnormalities involving signaling pathways other than NF-κB as mechanism of resistance to immune-chemotherapy. Our review suggests that NF-κB pathway is an important crossroad where other pathways converge as phenotype of resistance that emerges in patients who fail frontline and salvage immune-chemotherapy. Future efforts should aim at targeting the role of NF-κB resistance in clinical trials, where novel agents like lenalidomide and proteasome inhibitors with established activity in this perspective will be an important component in combination therapy, along with new monoclonal antibody, BTK-inhibitors, and other novel therapy agents. Francesco Turturro Copyright © 2015 Francesco Turturro. All rights reserved. Clinical Characteristics of Autism Spectrum Disorder in Israel: Impact of Ethnic and Social Diversities Thu, 23 Apr 2015 13:44:42 +0000 Despite the increased global prevalence and recognition of autistic spectrum disorder (ASD), it is still scarcely reported in the Arab world. Though Israel has a higher prevalence of ASD, a previous national survey of patients diagnosed between 1972 and 2004, demonstrated that 98% of them were of Jewish ancestry. The disproportional low number of Arab children with ASD in Israel is unclear but may reflect lower awareness and cultural bias. In the present study we collected clinical and demographic characteristics of 200 children with ASD from Arab and Jewish sectors in Israel that were evaluated in two child development centers. We compared the incidence and the medical comorbidity of autism between these two ethnics groups. The medical and psychiatric comorbidity profile in these children was similar to the worldwide published studies. In the present study the prevalence of autism in the Arab sector in Israel was similar to that of the Jewish sector. The Arab patients presented with more severe autistic manifestations and higher incidence of mental retardation, familial members with autism, and consanguinity (), while in the Jewish sector milder forms (such as Asperger syndrome and PDD-NOS) were more frequent. This discrepancy might be explained by both genetic and cultural factors. Muhammad Mahajnah, Rajech Sharkia, Haitham Shalabe, Ruth Terkel-Dawer, Ashraf Akawi, and Nathanel Zelnik Copyright © 2015 Muhammad Mahajnah et al. All rights reserved. Extramedullary Manifestation in Multiple Myeloma Bears High Incidence of Poor Cytogenetic Aberration and Novel Agents Resistance Thu, 23 Apr 2015 13:30:00 +0000 Extramedullary disease (EMD) in multiple myeloma (MM) patients is an uncommon event and more attention was directed toward the feature of these patients. Cytogenetic aberration is an important characteristic of MM and is associated with patients’ outcome. In this study, we aimed to compare the cytogenetic abnormality of patients with and without extramedullary manifestation, and to analyze the clinical outcomes of novel agents in EMD patients. We retrospectively investigated data from 41 MM patients. Our analyses showed del(17p13) in 31% of EMD versus 13% of medullary disease () and amp(1q21) in 55% versus 32% (). No differences were shown in del(13q14) and t(4;14). 24/27 patients with EMD at diagnosis responded to the novel agents-containing regimens. However, when relapsed, 70% of patients did not benefit from the sequential use of novel agents as salvage therapy. In 14 patients who developed EMD at relapse phase, only 2 patients responded to novel agents therapy. Median overall survival of patients with extramedullary manifestations was 30 months, in comparison to 104 months for patients without EMD (). Patients with extramedullary manifestation bore high incidence of poor cytogenetic aberration and novel agents resistance. Xiaoyan Qu, Lijuan Chen, Hairong Qiu, Hua Lu, Hanxin Wu, Hongxia Qiu, Peng Liu, Rui Guo, and Jianyong Li Copyright © 2015 Xiaoyan Qu et al. All rights reserved. Indoor Air Quality and Respiratory Health among Malay Preschool Children in Selangor Thu, 23 Apr 2015 12:41:22 +0000 Indoor air quality (IAQ) has been the object of several studies due to its adverse health effects on children. Methods. A cross-sectional comparative study was carried out among Malay children in Balakong (2 studied preschools) and Bangi (2 comparative preschools), Selangor, with the aims of determining IAQ and its association with respiratory health. 61 and 50 children aged 5-6 years were selected as studied and comparative groups. A questionnaire was used to obtain an exposure history and respiratory symptoms. Lung function test was carried out. IAQ parameters obtained include indoor concentration of particulate matter (PM), volatile organic compounds (VOCs), carbon monoxide (CO), carbon dioxide (CO2), temperature, air velocity (AV), and relative humidity. Results. There was a significant difference between IAQ in studied and comparative preschools for all parameters measured except for CO2 and AV. Studied preschools had higher PM and CO concentration. FVC, FEV1, FVC% and FEV1% predicted values were significantly lower among studied group. Exposures to PM, VOCs, and CO were associated with wheezing. Conclusion. The finding concluded that exposures to poor IAQ might increase the risk of getting lung function abnormality and respiratory problems among study respondents. Nur Azwani Mohd Nor Rawi, Juliana Jalaludin, and Poh Choo Chua Copyright © 2015 Nur Azwani Mohd Nor Rawi et al. All rights reserved. Biomarker as a Research Tool in Linking Exposure to Air Particles and Respiratory Health Thu, 23 Apr 2015 12:33:49 +0000 Some of the environmental toxicants from air pollution include particulate matter (PM10), fine particulate matter (PM2.5), and ultrafine particles (UFP). Both short- and long-term exposure could result in various degrees of respiratory health outcomes among exposed persons, which rely on the individuals’ health status. Methods. In this paper, we highlight a review of the studies that have used biomarkers to understand the association between air particles exposure and the development of respiratory problems resulting from the damage in the respiratory system. Data from previous epidemiological studies relevant to the application of biomarkers in respiratory system damage reported from exposure to air particles are also summarized. Results. Based on these analyses, the findings agree with the hypothesis that biomarkers are relevant in linking harmful air particles concentrations to increased respiratory health effects. Biomarkers are used in epidemiological studies to provide an understanding of the mechanisms that follow airborne particles exposure in the airway. However, application of biomarkers in epidemiological studies of health effects caused by air particles in both environmental and occupational health is inchoate. Conclusion. Biomarkers unravel the complexity of the connection between exposure to air particles and respiratory health. Nur Faseeha Suhaimi and Juliana Jalaludin Copyright © 2015 Nur Faseeha Suhaimi and Juliana Jalaludin. All rights reserved. A Novel Loss-of-Sclerostin Function Mutation in a First Egyptian Family with Sclerosteosis Thu, 23 Apr 2015 11:13:26 +0000 Sclerosteosis is a rare autosomal recessive condition characterized by increased bone density. Mutations in SOST gene coding for sclerostin are linked to sclerosteosis. Two Egyptian brothers with sclerosteosis and their apparently normal consanguineous parents were included in this study. Clinical evaluation and genomic sequencing of the SOST gene were performed followed by in silico analysis of the resulting variation. A novel homozygous frameshift mutation in the SOST gene, characterized as one nucleotide cytosine insertion that led to premature stop codon and loss of functional sclerostin, was identified in the two affected brothers. Their parents were heterozygous for the same mutation. To our knowledge this is the first Egyptian study of sclerosteosis and SOST gene causing mutation. Alaaeldin Fayez, Mona Aglan, Nora Esmaiel, Taher El Zanaty, Mohamed Abdel Kader, and Mona El Ruby Copyright © 2015 Alaaeldin Fayez et al. All rights reserved. Changes of the eSheath Outer Dimensions Used for Transfemoral Transcatheter Aortic Valve Replacement Thu, 23 Apr 2015 11:01:35 +0000 Innovative catheter systems with lower-profile sheaths and a dynamic expansion mechanism (DEM) were recently introduced for transcatheter aortic valve replacement (TAVR). However, the labeling of 14 F and 16 F eSheaths denote the inner nominal diameter. Exact changes of the clinically relevant outer diameters during usage are not available. eSheaths were measured every 30 mm using a digital caliper. Unused 14 F and 16 F eSheaths served as controls. Maximum eSheath diameters were measured after insertion of the Edwards Commander Delivery System (ECDS) into 14 F and 16 F eSheaths.Finally, eSheaths were retrieved and measured after TAVR. Outer diameters of control 14 F eSheaths were 5.8 mm and 6.50 mm for the 16 F eSheath. Introduction of the 23 mm and 26 mm ECDS into 14 F eSheaths showed a maximum diameter of 7.65 mm and 7.64 mm (). Introduction of the 29 mm ECDS into the 16 F eSheath showed the greatest diameter of 8.18 mm (). After TAVR, diameters of the 14 F eSheaths were 7.14 mm (23 mm valve) and 7.26 mm (26 mm valve) (), while 16 F eSheaths were 8.10 mm (29 mm valve) (). Nominal 14 F and 16 F eSheaths showed a significant increase of the outer diameter during advancement of the ECDS and after TAVR implantation. Till Koehler, Michael Buege, Heinrich Schleiting, Melchior Seyfarth, Klaus Tiroch, and Marc Vorpahl Copyright © 2015 Till Koehler et al. All rights reserved. Recent Advances and Future Perspective in Microbiota and Probiotics Thu, 23 Apr 2015 07:59:27 +0000 Haruki Kitazawa, Susana Alvarez, Alexander Suvorov, Vyacheslav Melnikov, Julio Villena, and Borja Sánchez Copyright © 2015 Haruki Kitazawa et al. All rights reserved. Implants in Urogynecology Thu, 23 Apr 2015 06:56:44 +0000 Thomas Otto, Bernd Klosterhalfen, Uwe Klinge, Mihaly Boros, Dirk Ysebaert, and Koudy Williams Copyright © 2015 Thomas Otto et al. All rights reserved. Corrigendum to “Synergistic Effects of Toxic Elements on Heat Shock Proteins” Thu, 23 Apr 2015 06:51:45 +0000 Khalid Mahmood, Saima Jadoon, Qaisar Mahmood, Muhammad Irshad, and Jamshaid Hussain Copyright © 2015 Khalid Mahmood et al. All rights reserved. Neurotensin Branched Peptide as a Tumor-Targeting Agent for Human Bladder Cancer Thu, 23 Apr 2015 06:44:40 +0000 Despite recent advances in multimodal therapy, bladder cancer still ranks ninth in worldwide cancer incidence. New molecules which might improve early diagnosis and therapeutic efficiency for tumors of such high epidemiological impact therefore have very high priority. In the present study, the tetrabranched neurotensin peptide NT4 was conjugated with functional units for cancer-cell imaging or therapy and was tested on bladder cancer cell lines and specimens from bladder cancer surgical resections, in order to evaluate its potential for targeted personalized therapy of bladder cancer. Fluorophore-conjugated NT4 distinguished healthy and cancer tissues with good statistical significance . NT4 conjugated to methotrexate or gemcitabine was cytotoxic for human bladder cancer cell lines at micromolar concentrations. Their selectivity for bladder cancer tissue and capacity to carry tracers or drugs make NT4 peptides candidate tumor targeting agents for tracing cancer cells and for personalized therapy of human bladder cancer. Jlenia Brunetti, Chiara Falciani, Barbara Lelli, Andrea Minervini, Niccolò Ravenni, Lorenzo Depau, Giampaolo Siena, Eleonora Tenori, Stefano Menichetti, Alessandro Pini, Marco Carini, and Luisa Bracci Copyright © 2015 Jlenia Brunetti et al. All rights reserved. A Comprehensive Systems Biological Study of Autophagy-Apoptosis Crosstalk during Endoplasmic Reticulum Stress Thu, 23 Apr 2015 06:23:34 +0000 One of the most important tasks of a living organism is to maintain its genetic integrity with respect to stress. Endoplasmic reticulum (ER) has a crucial role in sensing cellular homeostasis by controlling metabolism, proteostasis, and several signaling processes. ER stressors can induce autophagy-dependent survival; however excessive level of stress results in apoptotic cell death. Although many molecular components of these networks have already been discovered, the analysis of the dynamical features of the regulatory network of life-or-death decision is still lacking. Our goal was to incorporate both theoretical and molecular biological techniques to explore the autophagy-apoptosis crosstalk under ER stress. Using various levels of different ER stressors we confirmed that the control network always generated an evidently detectable autophagy-dependent threshold for apoptosis activation. We explored the features of this threshold by introducing both autophagy activators and inhibitors, and transient treatment with excessive level of ER stressor was also performed. Our experimental data were also supported by a stochastic approach. Our analysis suggests that even if the switch-like characteristic of apoptosis activation is hardly seen on population level the double negative feedback loop between autophagy and apoptosis inducers introduces bistability in the control network. Marianna Holczer, Margita Márton, Anita Kurucz, Gábor Bánhegyi, and Orsolya Kapuy Copyright © 2015 Marianna Holczer et al. All rights reserved. Correlation between the Pharyngeal Airway Space and Head Posture after Surgery for Mandibular Prognathism Wed, 22 Apr 2015 13:11:40 +0000 Purpose. The aim of this study was to determine the correlation between the pharyngeal airway space and head posture after mandibular setback surgery for mandibular prognathism. Materials and Methods. Serial lateral cephalograms of 37 patients with mandibular prognathism who underwent intraoral vertical ramus osteotomy (IVRO) were evaluated before (T1) and immediately (T2), between 6 weeks and 3 months (T3), and more than 1 year (T4) after surgery. Paired t-tests and Pearson’s correlation analysis were used to evaluate the postoperative changes in all cephalometric parameters, including the mandible, hyoid, head posture (craniocervical angle), and pharyngeal airway space. Results. The mandible and hyoid were set back by 12.8 mm and 4.9 mm, respectively, at T2. Furthermore, the hyoid showed significant inferior movement of 10.7 mm, with an 8 mm increase in the tongue depth. The upper oropharyngeal airway (UOP) shortened by 4.1 mm, the lower oropharyngeal airway (LOP) by 1.7 mm, and the laryngopharyngeal airway by 2 mm. The craniocervical angle showed a significant increase of 2.8°. UOP and LOP showed a significant correlation with the craniocervical angle at T2 and T4. Conclusions. Our findings conclude that the oropharyngeal airway space is significantly decreased and correlated with a change in the head posture after mandibular setback surgery. Chun-Ming Chen, Steven Lai, Ker-Kong Chen, and Huey-Er Lee Copyright © 2015 Chun-Ming Chen et al. All rights reserved. Ca2+ Signaling in Cytoskeletal Reorganization, Cell Migration, and Cancer Metastasis Wed, 22 Apr 2015 12:32:59 +0000 Proper control of Ca2+ signaling is mandatory for effective cell migration, which is critical for embryonic development, wound healing, and cancer metastasis. However, how Ca2+ coordinates structural components and signaling molecules for proper cell motility had remained elusive. With the advance of fluorescent live-cell Ca2+ imaging in recent years, we gradually understand how Ca2+ is regulated spatially and temporally in migrating cells, driving polarization, protrusion, retraction, and adhesion at the right place and right time. Here we give an overview about how cells create local Ca2+ pulses near the leading edge, maintain cytosolic Ca2+ gradient from back to front, and restore Ca2+ depletion for persistent cell motility. Differential roles of Ca2+ in regulating various effectors and the interaction of roles of Ca2+ signaling with other pathways during migration are also discussed. Such information might suggest a new direction to control cancer metastasis by manipulating Ca2+ and its associating signaling molecules in a judicious manner. Feng-Chiao Tsai, Guan-Hung Kuo, Shu-Wei Chang, and Pei-Ju Tsai Copyright © 2015 Feng-Chiao Tsai et al. All rights reserved. High Variability of Fabry Disease Manifestations in an Extended Italian Family Wed, 22 Apr 2015 06:28:42 +0000 Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL). The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease. Giuseppe Cammarata, Pasquale Fatuzzo, Margherita Stefania Rodolico, Paolo Colomba, Luigi Sicurella, Francesco Iemolo, Carmela Zizzo, Riccardo Alessandro, Caterina Bartolotta, Giovanni Duro, and Ines Monte Copyright © 2015 Giuseppe Cammarata et al. All rights reserved. Functional Genomics, Genetics, and Bioinformatics Wed, 22 Apr 2015 06:20:06 +0000 Youping Deng, Hongwei Wang, Ryuji Hamamoto, David Schaffer, and Shiwei Duan Copyright © 2015 Youping Deng et al. All rights reserved. How Do Families of Children with Down Syndrome Perceive Speech Intelligibility in Turkey? Tue, 21 Apr 2015 14:08:53 +0000 Childhood verbal apraxia has not been identified or treated sufficiently in children with Down syndrome but recent research has documented that symptoms of childhood verbal apraxia can be found in children with Down syndrome. But, it is not routinely diagnosed in this population. There is neither an assessment tool in Turkish nor any research on childhood verbal apraxia although there is a demand not only for children with Down syndrome but also for normally developing children. The study examined if it was possible to determine oral-motor difficulties and childhood verbal apraxia features in children with Down syndrome through a survey. The survey was a parental report measure. There were 329 surveys received. Results indicated that only 5.6% of children with Down syndrome were diagnosed with apraxia, even though many of the subject children displayed clinical features of childhood verbal apraxia. The most frequently reported symptoms of childhood verbal apraxia in literature were displayed by the children with Down syndrome in the study. Parents could identify childhood verbal apraxia symptoms using parent survey. This finding suggests that the survey can be developed that could serve as a screening tool for a possible childhood verbal apraxia diagnosis in Turkey. Bülent Toğram Copyright © 2015 Bülent Toğram. All rights reserved. Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus Tue, 21 Apr 2015 14:04:26 +0000 Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage. Montserrat Batlle, Lorenzo Ferri, Carmen Andrade, Francisco-Javier Ortega, Jose M. Vidal-Taboada, Marco Pugliese, Nicole Mahy, and Manuel J. Rodríguez Copyright © 2015 Montserrat Batlle et al. All rights reserved. Intrinsic Immunomodulatory Effects of Low-Digestible Carbohydrates Selectively Extend Their Anti-Inflammatory Prebiotic Potentials Tue, 21 Apr 2015 13:34:02 +0000 The beneficial effects of carbohydrate-derived fibers are mainly attributed to modulation of the microbiota, increased colonic fermentation, and the production of short-chain fatty acids. We studied the direct immune responses to alimentary fibers in in vitro and in vivo models. Firstly, we evaluated the immunomodulation induced by nine different types of low-digestible fibers on human peripheral blood mononuclear cells. None of the fibers tested induced cytokine production in baseline conditions. However, only one from all fibers almost completely inhibited the production of anti- and proinflammatory cytokines induced by bacteria. Secondly, the impact of short- (five days) and long-term (three weeks) oral treatments with selected fibers was assessed in the trinitrobenzene-sulfonic acid colitis model in mice. The immunosuppressive fiber significantly reduced levels of inflammatory markers over both treatment periods, whereas a nonimmunomodulatory fiber had no effect. The two fibers did not differ in terms of the observed fermentation products and colonic microbiota after three weeks of treatment, suggesting that the anti-inflammatory action was not related to prebiotic properties. Hence, we observed a direct effect of a specific fiber on the murine immune system. This intrinsic, fiber-dependent immunomodulatory potential may extend prebiotic-mediated protection in inflammatory bowel disease. Jérôme Breton, Coline Plé, Laetitia Guerin-Deremaux, Bruno Pot, Catherine Lefranc-Millot, Daniel Wils, and Benoit Foligné Copyright © 2015 Jérôme Breton et al. All rights reserved. Implications of Green Tea and Its Constituents in the Prevention of Cancer via the Modulation of Cell Signalling Pathway Tue, 21 Apr 2015 13:23:29 +0000 Green tea is commonly used as a beverage worldwide, especially in China, Japan, Morocco, and Saudi Arabia. Green tea and its constituents have been considered very effective in the prevention and treatment of various diseases. It contains a variety of catechins, which show a pivotal role in the modulation of biological activities and also act as chemopreventive agents. Earlier studies have confirmed that green tea and its chief constituent epigallocatechin gallate (EGCG) have a potential role in the management of cancer through the modulation of cell signaling pathways. In this review, we focused on the beneficial effects of green tea and its constituents in the cancer prevention and treatment and its impact on modulation of molecular pathways. Arshad H. Rahmani, Fahad M. Al shabrmi, Khaled S. Allemailem, Salah M. Aly, and Masood A. Khan Copyright © 2015 Arshad H. Rahmani et al. All rights reserved. Binding of Citreoviridin to Human Serum Albumin: Multispectroscopic and Molecular Docking Tue, 21 Apr 2015 12:56:29 +0000 Citreoviridin (CIT), a mycotoxin produced by Penicillium citreonigrum, is a common contaminant of wide range of agriproducts and detrimental to human and animal health. In this study, the interaction of CIT with human serum albumin (HSA) is researched by steady-state fluorescence, ultraviolet-visible (UV-Vis) absorption, circular dichroism (CD) methods, and molecular modeling. The association constants, binding site numbers, and corresponding thermodynamic parameters are used to investigate the quenching mechanism. The alternations of HSA secondary structure in the presence of CIT are demonstrated with UV-Vis, synchronous fluorescence, and CD spectra. The molecular modeling results reveal that CIT can bind with hydrophobic pocket of HSA with hydrophobic and hydrogen bond force. Moreover, an apparent distance of 3.25 nm between Trp214 and CIT is obtained via fluorescence resonance energy transfer method. Haifeng Hou, Xiaolan Qu, Yuqin Li, Yueyue Kong, Baoxiu Jia, Xiaojun Yao, and Baofa Jiang Copyright © 2015 Haifeng Hou et al. All rights reserved. Anti-Lung Cancer Activity of the Curcumin Analog JZ534 In Vitro Tue, 21 Apr 2015 08:14:38 +0000 This study investigated the anticancer effect of the curcumin analog JZ534 on lung cancer cell lines H460, A549, H1975, and HCC827. The antiproliferation effect of JZ534 was measured through the methylthiazoletetrazolium assay, and cell colony formation was observed. Cell cycle and apoptosis were determined by flow cytometry, and the preliminary mechanism was studied by Western blot. Results showed that JZ534 significantly inhibited the vitality and colony formation of lung cancer cells. JZ534 induced the G2/M cell cycle arrest of the cancer cells and suppressed the expression of cycle-related proteins, including cyclin B1 and Cdc2. Meanwhile, JZ534 induced cell apoptosis and upregulated the expression of apoptosis-related proteins, including cleaved caspase-3, Bax, and p53. At the same dose, JZ534 showed better antitumor activity than curcumin. These results suggest that JZ534 exhibits excellent anti-lung cancer activity by inhibiting the growth and inducing the apoptosis of lung cancer cells. Therefore, JZ534 is a promising lead compound for cancer treatment. Jianzhang Wu, Zhijian Cai, Xiaoyan Wei, Minxiao Chen, Shilong Ying, Lingyi Shi, Ren-Ai Xu, Fan He, Guang Liang, and Xiuhua Zhang Copyright © 2015 Jianzhang Wu et al. All rights reserved. Functional Polymorphisms in COX-2 Gene Are Correlated with the Risk of Oral Cancer Tue, 21 Apr 2015 07:53:52 +0000 Background. This meta-analysis investigated the association between functional COX-2 gene polymorphisms and the risk of oral cancer. Methods. Several electronic databases were searched for published studies using combinations of keywords related to COX-2 gene polymorphisms and oral cancer. After selection of relevant studies, following strict inclusion and exclusion criteria, data was performed using STATA 12.0 software. Results. We retrieved 83 studies from database search using specific search terms. After multiple rounds of selection and elimination, 7 studies were finally identified as suitable to be included in our present meta-analysis, based on their relevance and data integrity. These 7 studies contained a combined total of 2,296 oral cancer patients and 3,647 healthy controls. Our findings demonstrated that +837 T > C (rs5275) polymorphism in COX-2 showed statistically significant differences in gene frequencies in case and control groups in allele model and dominant model. Similar results were obtained with COX-2 gene polymorphism 765 G > C (rs20417). On the other hand, 1195 A > G (rs689466) polymorphism in COX-2 did not confer susceptibility to oral cancers. Conclusion. Based on our results, COX-2 gene polymorphisms, +837 T > C (rs5275) and −765G > C (rs20417), showed clear links with oral cancer susceptibility, and the 1195A > G (rs689466) polymorphism did not show such a correlation. Dong Li, Shu-Hong Hao, Yan Sun, Chun-Mei Hu, Zhi-Hua Ma, Zhi Ming Wang, Jie Liu, Hong Bo Liu, Ming Ye, Yu Fei Zhang, Dong Sheng Yang, and Guang Shi Copyright © 2015 Dong Li et al. All rights reserved. Biomaterials for Pelvic Floor Reconstructive Surgery: How Can We Do Better? Tue, 21 Apr 2015 06:26:33 +0000 Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes. Giulia Gigliobianco, Sabiniano Roman Regueros, Nadir I. Osman, Julio Bissoli, Anthony J. Bullock, Chris R. Chapple, and Sheila MacNeil Copyright © 2015 Giulia Gigliobianco et al. All rights reserved. Benchtop Technologies for Circulating Tumor Cells Separation Based on Biophysical Properties Tue, 21 Apr 2015 06:04:13 +0000 Circulating tumor cells (CTCs) are tumor cells that have detached from primary tumor site and are transported via the circulation system. The importance of CTCs as prognostic biomarker is leveraged when multiple studies found that patient with cutoff of 5 CTCs per 7.5 mL blood has poor survival rate. Despite its clinical relevance, the isolation and characterization of CTCs can be quite challenging due to their large morphological variability and the rare presence of CTCs within the blood. Numerous methods have been employed and discussed in the literature for CTCs separation. In this paper, we will focus on label free CTCs isolation methods, in which the biophysical and biomechanical properties of cells (e.g., size, deformability, and electricity) are exploited for CTCs detection. To assess the present state of various isolation methods, key performance metrics such as capture efficiency, cell viability, and throughput will be reported. Finally, we discuss the challenges and future perspectives of CTC isolation technologies. Wan Shi Low and Wan Abu Bakar Wan Abas Copyright © 2015 Wan Shi Low and Wan Abu Bakar Wan Abas. All rights reserved. Complications following Tension-Free Vaginal Tapes: Accurate Diagnosis and Complications Management Mon, 20 Apr 2015 13:33:59 +0000 The sling procedures are the gold standard for SUI treatment. They are highly effective but not free from complications. The most common adverse effect for the surgery with the implant insertion is: overactive bladder occurring de novo after the surgery, voiding dysfunctions, urine retention, and unsatisfactory treatment outcome. The most important question that arises after 20 years of sling procedures is how to manage the complications and what can be offered to complicated patients. The above review summarises the ultrasound findings in complicated cases and shows the scheme of management of the clinical problems concerning the tape location in suburethral region. J. Kociszewski, S. Kolben, D. Barski, V. Viereck, and E. Barcz Copyright © 2015 J. Kociszewski et al. All rights reserved. High Structural Stability of Textile Implants Prevents Pore Collapse and Preserves Effective Porosity at Strain Mon, 20 Apr 2015 11:21:22 +0000 Reinforcement of tissues by use of textiles is encouraged by the reduced rate of recurrent tissue dehiscence but for the price of an inflammatory and fibrotic tissue reaction to the implant. The latter mainly is affected by the size of the pores, whereas only sufficiently large pores are effective in preventing a complete scar entrapment. Comparing two different sling implants (TVT and SIS), which are used for the treatment of urinary incontinence, we can demonstrate that the measurement of the effective porosity reveals considerable differences in the textile construction. Furthermore the changes of porosity after application of a tensile load can indicate a structural instability, favouring pore collapse at stress and questioning the use for purposes that are not “tension-free.” Uwe Klinge, Jens Otto, and Thomas Mühl Copyright © 2015 Uwe Klinge et al. All rights reserved. The Influence of Metabolic Factors for Nonalcoholic Fatty Liver Disease in Women Mon, 20 Apr 2015 09:57:30 +0000 Background/Aims. Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women. Methods. A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited. Results. Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%, ). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD. Conclusions. Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women. Goh Eun Chung, Jeong Yoon Yim, Donghee Kim, Seon Hee Lim, Jong In Yang, Young Sun Kim, Sun Young Yang, Min-Sun Kwak, Joo Sung Kim, and Sang-Heon Cho Copyright © 2015 Goh Eun Chung et al. All rights reserved. Integrated Analysis of Multiscale Large-Scale Biological Data for Investigating Human Disease Mon, 20 Apr 2015 09:13:13 +0000 Tao Huang, Lei Chen, Mingyue Zheng, and Jiangning Song Copyright © 2015 Tao Huang et al. All rights reserved. Global Convergence on the Bioethics of Surgical Implants Mon, 20 Apr 2015 09:02:50 +0000 The increasing globalization of mankind with pluralistic belief systems necessitates physicians by virtue of their profession to partner with bioethics for soundly applying emerging knowledge and technologies for the best use of the patient. A subfield within medicine in which this need is acutely felt is that of surgical implants. Within this subfield such recent promising ethics and medicine partnerships include the International Tissue Engineering Research Association and UNESCO Chair in Bioethics and Human Rights’ International Code of Ethics. In this paper, we provide an overview of the emerging human rights framework from bioethics and international law, discussion of key framework principles, their application to the current surgical challenge of implantation of surgical mesh for prolapse, and conclusions and recommendations. Such discussions are meant to facilitate true quality improvement in patient care by ensuring the exciting technologies and medical practices emerging new daily are accompanied by an equal commitment of physicians to ethically provide their services for the chief end of the patient’s good. Alberto Garcia and Dominique J. Monlezun Copyright © 2015 Alberto Garcia and Dominique J. Monlezun. All rights reserved.