BioMed Research International http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders Wed, 22 Oct 2014 12:05:37 +0000 http://www.hindawi.com/journals/bmri/2014/670842/ A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities. Taha Faruqi, Naveen Dhawan, Jaya Bahl, Vineet Gupta, Shivani Vohra, Khin Tu, and Samir M. Abdelmagid Copyright © 2014 Taha Faruqi et al. All rights reserved. Development of a Finite Element Head Model for the Study of Impact Head Injury Wed, 22 Oct 2014 10:49:26 +0000 http://www.hindawi.com/journals/bmri/2014/408278/ This study is aimed at developing a high quality, validated finite element (FE) human head model for traumatic brain injuries (TBI) prediction and prevention during vehicle collisions. The geometry of the FE model was based on computed tomography (CT) and magnetic resonance imaging (MRI) scans of a volunteer close to the anthropometry of a 50th percentile male. The material and structural properties were selected based on a synthesis of current knowledge of the constitutive models for each tissue. The cerebrospinal fluid (CSF) was simulated explicitly as a hydrostatic fluid by using a surface-based fluid modeling method. The model was validated in the loading condition observed in frontal impact vehicle collision. These validations include the intracranial pressure (ICP), brain motion, impact force and intracranial acceleration response, maximum von Mises stress in the brain, and maximum principal stress in the skull. Overall results obtained in the validation indicated improved biofidelity relative to previous FE models, and the change in the maximum von Mises in the brain is mainly caused by the improvement of the CSF simulation. The model may be used for improving the current injury criteria of the brain and anthropometric test devices. Bin Yang, Kwong-Ming Tse, Ning Chen, Long-Bin Tan, Qing-Qian Zheng, Hui-Min Yang, Min Hu, Gang Pan, and Heow-Pueh Lee Copyright © 2014 Bin Yang et al. All rights reserved. Comparison of Structural Architecture of HCV NS3 Genotype 1 versus Pakistani Genotype 3a Tue, 21 Oct 2014 13:49:18 +0000 http://www.hindawi.com/journals/bmri/2014/749254/ This study described the structural characterization of Pakistani HCV NS3 GT3a in parallel with genotypes 1a and 1b NS3. We investigated the role of amino acids and their interaction patterns in different HCV genotypes by crystallographic modeling. Different softwares were used to study the interaction pattern, for example, CLCBIO sequence viewer, MODELLER, NMRCLUST, ERRAT score, and MODELLER. Sixty models were produced and clustered into groups and the best model of PK-NCVI/Pk3a NS3 was selected and studied further to check the variability with other HCV NS3 genotypes. This study will help in future to understand the structural architecture of HCV genome variability and to further define the conserved targets for antiviral agents. Kaneez Fatima, Esam Azhar, Shilu Mathew, Ghazi Damanhouri, and Ishtiaq Qadri Copyright © 2014 Kaneez Fatima et al. All rights reserved. Antidiabetic Activity of Pterospermum acerifolium Flowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint Tue, 21 Oct 2014 08:43:33 +0000 http://www.hindawi.com/journals/bmri/2014/459376/ The present study was designed to estimate the detailed antidiabetic activity of Pterospermum acerifolium (L.) Willd flowers. In vitro alpha amylase inhibition study was carried out on 50% ethanol extract of flowers (PAFEE) and its various fractions. The active ethyl acetate fraction (PAFEF) was subfractionated into three subfractions (PAFE1, PAFE2, and PAFE3) and subjected to acute toxicity studies followed by antidiabetic screening in vivo by streptozotocin-nicotinamide induced type II diabetes. Diabetic animals treated with PAFE2 (30 mg/kg) reduced the levels of fasting blood glucose, significantly () compared to that of diabetic control animals. Histological studies on drug treated groups did not show remarkable positive changes in β-cells. PAFE2 showed % glucose uptake over control and, in the presence of PI3K inhibitor wortmannin, declined to %. HPLC analysis of PAFE2 reveals the presence of quercetin and apigenin as major constituents and both are inhibiting the glycogen phosphorylase enzyme in molecular modelling studies. The study evidenced strongly that the probable glucose lowering mechanism of action of active subfraction PAFE2 is by increasing the glucose uptake in peripheral tissues and by inhibition of gluconeogenesis. Rathinavelusamy Paramaguru, Papiya Mitra Mazumder, Dinakar Sasmal, and Venkatesan Jayaprakash Copyright © 2014 Rathinavelusamy Paramaguru et al. All rights reserved. Identification of Endothelial Progenitor Cells in the Corpus Cavernosum in Rats Tue, 21 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/910564/ The vascular wall resident progenitor cells seem to serve as a local reservoir of cells for vascular repair. It was hypothesized that the corpus cavernosum may contain vascular wall endothelial progenitor cells (EPCs). In this study, we investigated the identification and localization of EPCs in the corpus cavernosum in a rat model. Adult male Sprague-Dawley rats were used to isolate EPCs from corpora cavernosum. To verify the existence and localization of EPCs, EPC-specific markers (CD34, Flk-1, and VE-cadherin) were evaluated by flow cytometric analysis and confocal microscopy. The EPC markers were mainly expressed in the cavernosal sinusoidal endothelial space. EPC-marker-positive cells made up about 3.31% of the corpus cavernosum of normal rat by FACS analysis. As shown by confocal microscopy, CD34+/Flk-1+ and CD34+/VE-cadherin+ positive cells existed in the corpus cavernosum. Our findings imply that regulation of corpus cavernosal EPCs may be a new therapeutic strategy in the treatment of erectile dysfunction. Jun Sik Lee, In Sang Hwang, Hyun-Suk Lee, Mi Eun Kim, Young-Woo Seo, and Kwangsung Park Copyright © 2014 Jun Sik Lee et al. All rights reserved. Activation of the AT1R/HIF-1α/ACE Axis Mediates Angiotensin II-Induced VEGF Synthesis in Mesenchymal Stem Cells Mon, 20 Oct 2014 11:47:30 +0000 http://www.hindawi.com/journals/bmri/2014/627380/ A local renin-angiotensin system (RAS) is expressed in mesenchymal stem cells (MSCs) and regulates stem cell function. The local RAS influences the survival and tissue repairing ability of transplanted stem cells. We have previously reported that angiotensin II (Ang II) pretreatment can significantly increase vascular endothelial growth factor (VEGF) synthesis in MSCs through the ERK1/2 and Akt pathways via the Ang II receptor type 1 (AT1R). However, the role of angiotensin-converting enzyme (ACE) has not been clarified. Furthermore, whether Ang II pretreatment activates hypoxia-inducible factor-1α (HIF-1α) in MSCs has not been elucidated. Our data show that both ACE and HIF-1α are involved in promoting VEGF expression in MSCs, and that both are upregulated by Ang II stimulation. The upregulation of ACE appeared after the rapid degradation of exogenous Ang II, and led to the formation of endogenous Ang II. On the other hand, the ACE inhibitor, captopril, attenuated Ang II-enhanced HIF-1α upregulation, while HIF-1α suppression markedly attenuated ACE expression. This interesting finding suggests an interaction between ACE and HIF-1α. We conclude that Ang II pretreatment, as a trigger, activated the AT1R/HIF-1α/ACE axis that then mediated Ang II-induced VEGF synthesis in MSCs. Chao Liu, Jing-Wen Zhang, Liang Hu, Yi-Chen Song, Lu Zhou, Yue Fan, Hong-Yi Zhu, Yu Wang, and Qing-Ping Li Copyright © 2014 Chao Liu et al. All rights reserved. Deregulation of Serum MicroRNA Expression Is Associated with Cigarette Smoking and Lung Cancer Mon, 20 Oct 2014 09:28:51 +0000 http://www.hindawi.com/journals/bmri/2014/364316/ Lung cancer is the leading cause of cancer-related death and cigarette smoking is the main risk factor for lung cancer. Circulating microRNAs (miRNAs) are considered potential biomarkers of various cancers, including lung cancer. However, it is unclear whether changes in circulating miRNAs are associated with smoking and smoking-related lung cancer. In this study, we determined the serum miRNA profiles of 10 nonsmokers, 10 smokers, and 10 lung-cancer patients with miRCURY LNA microRNA arrays. The differentially expressed miRNAs were then confirmed in a larger sample. We found that let-7i-3p and miR-154-5p were significantly downregulated in the sera of smokers and lung-cancer patients, so the serum levels of let-7i-3p and miR-154-5p are associated with smoking and smoking-related lung cancer. The areas under receiver operating characteristic curves for let-7i-3p and miR-154-5p were approximately 0.892 and 0.957, respectively. In conclusion, our results indicate that changes in serum miRNAs are associated with cigarette smoking and lung cancer and that let-7i-3p and miR-154-5p are potential biomarkers of smoking-related lung cancer. Jinkun Huang, Jianjun Wu, Yuanqi Li, Xun Li, Ti Yang, Qiaoyuan Yang, and Yiguo Jiang Copyright © 2014 Jinkun Huang et al. All rights reserved. Genetic Diversity of SCN5A Gene and Its Possible Association with the Concealed Form of Brugada Syndrome Development in Polish Group of Patients Mon, 20 Oct 2014 09:14:39 +0000 http://www.hindawi.com/journals/bmri/2014/462609/ Brugada Syndrome (BS) is an inherited channelopathy associated with a high incidence of sudden cardiac death. The paper presents the discovery of new genetic variants of SCN5A gene which might be associated with the development of a concealed form of Brugada Syndrome. The study involved a group of 59 patients (37 men) with suspected concealed form of Brugada Syndrome. Pharmacological provocation with intravenous ajmaline administration was performed. Six patients with positive test results were subjected to molecular analysis of SCN5A gene with MSSCP method. Additionally, MSSCP genotyping was performed for samples obtained from the family members with Brugada Syndrome, despite the fact that they had negative ajmaline challenge test results. Genetic examinations of the SCN5A gene at 6 positive patients showed 6 known polymorphisms, 8 new single nucleotide point (SNP) variants located at exons, and 12 new single nucleotide point variants located at introns. Among new SNPs localized in SCN5A gene exons three SNPs affected the protein sequence. Beata Uziębło-Życzkowska, Grzegorz Gielerak, Paweł Siedlecki, and Beata Pająk Copyright © 2014 Beata Uziębło-Życzkowska et al. All rights reserved. Genetic Multipartitions Based on D-Loop Sequences and Chromosomal Patterns in Brown Chromis, Chromis multilineata (Pomacentridae), in the Western Atlantic Sun, 19 Oct 2014 11:45:01 +0000 http://www.hindawi.com/journals/bmri/2014/254698/ Connectivity levels among Brazilian reef fish fauna populations have attracted growing interest, mainly between mainland shores and oceanic islands. The Pomacentridae, whose phylogeographic patterns are largely unknown in the Atlantic, are a family of dominant fish in reef regions. We present data on the variability and population structure of damselfish Chromis multilineata in different areas along the northeast coast of Brazil and in the waters around the oceanic islands of Fernando de Noronha (FNA) and Saint Peter and Saint Paul Archipelago (SPSPA) through analysis of the HVR1 mtDNA sequence of the control region. The remote SPSPA exhibits the highest level of genetic divergence among populations. Conventional and molecular cytogenetic analysis showed similar karyotype patterns (2n = 48 acrocentrics) between these insular areas. Our estimates reveal three genetically different population groups of C. multilineata on the Brazilian coast. The level of genetic structure is higher than previous data suggested, indicating complex panel of interactions between the oceanic island and coastal populations of Brazil. Inailson Márcio Costa da Cunha, Allyson Santos de Souza, Eurico Azevedo Dias Jr., Karlla Danielle Jorge Amorim, Rodrigo Xavier Soares, Gideão Wagner Werneck Félix da Costa, Erik García-Machado, Pedro Manoel Galetti Jr., and Wagner Franco Molina Copyright © 2014 Inailson Márcio Costa da Cunha et al. All rights reserved. Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin Sun, 19 Oct 2014 08:23:16 +0000 http://www.hindawi.com/journals/bmri/2014/495091/ The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer’s disease, tauopathies, and Huntington’s diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell. Panchanan Maiti, Jayeeta Manna, Shobi Veleri, and Sally Frautschy Copyright © 2014 Panchanan Maiti et al. All rights reserved. Contribution of α,β-Amyrenone to the Anti-Inflammatory and Antihypersensitivity Effects of Aleurites moluccana (L.) Willd. Sun, 19 Oct 2014 07:26:25 +0000 http://www.hindawi.com/journals/bmri/2014/636839/ The aim of the study was to analyze the constituents of the dichloromethane fraction obtained from A. moluccana and also to evaluate the anti-inflammatory and antinociceptive properties of α,β-amyrenone isolated from A. moluccana in mice. The dichloromethane fraction was evaluated by gas chromatography and submitted to purification. The mixture of α,β-amyrenone was isolated and then evaluated using the carrageenan-induced paw-oedema or pleurisy and CFA-induced arthritis models in mice. Five triterpenes, α,β-amyrenone, glutinol, and α,β-amyrin were isolated from dichloromethane fraction of A. moluccana leaf extract. The mixture of α,β-amyrenone, dosed orally, was able to reduce mechanical hypersensitivity and paw-oedema induced by carrageenan, interfering with neutrophil migration. Similar results were observed in the carrageenan-induced pleurisy model. Repeated administration of the compounds was also effective in reducing the mechanical sensitization and oedema developed in the arthritis model induced by CFA. In conclusion, the results demonstrate that α,β-amyrenone interferes in both acute and chronic inflammatory processes. We can infer that these effects involve, at least in part, a reduction in the neutrophil migration. Therefore, it seems reasonable to suggest that α,β-amyrenone could represent a new therapeutic tool for the management of painful and inflammatory diseases, especially those presenting a chronic profile. Nara Lins Meira Quintão, Lilian W. Rocha, Gislaine Franciele Silva, Simone Reichert, Vanessa D. Claudino, Ruth Meri Lucinda-Silva, Angela Malheiros, Márcia Maria De Souza, Valdir Cechinel Filho, Tania M. Bellé Bresolin, Marina da Silva Machado, Theodoro Marcel Wagner, and Christiane Meyre-Silva Copyright © 2014 Nara Lins Meira Quintão et al. All rights reserved. Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis Thu, 16 Oct 2014 13:01:01 +0000 http://www.hindawi.com/journals/bmri/2014/691540/ Background. Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. Method. Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. Results. Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD = 1.36, 95%CI: 0.37–2.36, ). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD = 1.73, 95%CI: 0.20–3.26, ), but not in Asians (SMD = 1.04, 95%CI: −0.33–2.40, ). Conclusion. The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs. Ze-Lin Sun, Qi-Ying Xie, Gong-Liang Guo, Ke Ma, and Yuan-Yuan Huang Copyright © 2014 Ze-Lin Sun et al. All rights reserved. Downregulation of MDR1 Gene by Cepharanthine Hydrochloride Is Related to the Activation of c-Jun/JNK in K562/ADR Cells Thu, 16 Oct 2014 08:40:31 +0000 http://www.hindawi.com/journals/bmri/2014/164391/ The purpose of the study was to determine the signal transduction mechanism of cepharanthine hydrochloride (CH) on reversing tumor multidrug resistance. RT-PCR and Western blot analysis were used to determine the effects of CH on the expression of MDR1 mRNA and P-glycoprotein in K562/ADR cells when CH was used alone and combined with SP600125, a JNK inhibitor, to explore the effects of CH on JNK pathway. Western blot analysis was used to determine the effects of CH on c-Jun protein expression and phosphorylation, to explore the regulating effects of CH on c-Jun and phosphorylated c-Jun (p-c-Jun) proteins. Our results showed that the inhibitory effect of CH on MDR1 mRNA increased with the concentrations of CH (5.0, 10.0, and 20.0 μM) and the inhibitory effects of CH on MDR1 mRNA and P-glycoprotein increased with the incubation time of CH (0, 12, 24, 36, and 48 hours). The inhibitory effect was weakened after CH combined with SP600125. The expressions of c-Jun and p-c-Jun proteins increased with the incubation time of CH (0, 6, 12, and 24 hours). These findings suggest that CH downregulated the expressions of MDR1 mRNA and P-glycoprotein in a time and concentration manner; the mechanism may be mediated via activating c-Jun/JNK pathway. Li Han, Yafeng Wang, Xiaojuan Guo, Yubing Zhou, Jingmin Zhang, Ning Wang, Jinhua Jiang, Fang Ma, and Qingduan Wang Copyright © 2014 Li Han et al. All rights reserved. Advanced Tracers in PET Imaging of Cardiovascular Disease Wed, 15 Oct 2014 11:59:43 +0000 http://www.hindawi.com/journals/bmri/2014/504532/ Cardiovascular disease is the leading cause of death worldwide. Molecular imaging with targeted tracers by positron emission tomography (PET) allows for the noninvasive detection and characterization of biological changes at the molecular level, leading to earlier disease detection, objective monitoring of therapies, and better prognostication of cardiovascular diseases progression. Here we review, the current role of PET in cardiovascular disease, with emphasize on tracers developed for PET imaging of cardiovascular diseases. Yesen Li, Wei Zhang, Hua Wu, and Gang Liu Copyright © 2014 Yesen Li et al. All rights reserved. Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension: A Sensitive Tool for Detection of Subclinical LV Impairment Wed, 15 Oct 2014 07:32:52 +0000 http://www.hindawi.com/journals/bmri/2014/472562/ Early diagnosis of cardiac alterations in hypertensive heart disease is still challenging. Since such patients might have depressed global LV systolic strain or strain rate when EF is still normal, speckle-tracking echocardiography (STE) and tissue-Doppler imaging (TDI) combined with stress echocardiography might improve early diagnosis of cardiac alterations. In this prospective study standard 2D Doppler echocardiography, STE, and TDI were performed at rest and during bicycle exercise in 92 consecutive patients—46 hypertensive subjects with normal ejection fraction and 46 healthy controls. STE and TDI were used to measure global peak systolic LV circumferential strain (CS), longitudinal strain (LS), and longitudinal strain rate (SR). Mean arterial blood pressure was significantly higher in hypertensive patients at rest (100.8 mmHg SD 13.5 mmHg; ) and during physical exercise testing (124.2 mmHg SD 13.4 mmHg; ). Hypertensive patients had significantly reduced values of systolic CS (), LS (), and SR () at rest as well as during physical exercise—CS (), LS (), and SR (). Using STE and TDI, reduced LV systolic strain and strain rate consistent with early cardiac alterations can be detected in patients with arterial hypertension. These findings were evident at rest and markedly pronounced during exercise echocardiography. Kai O. Hensel, Andreas Jenke, and Roman Leischik Copyright © 2014 Kai O. Hensel et al. All rights reserved. A Novel Approach for Development and Characterization of Effective Mosquito Repellent Cream Formulation Containing Citronella Oil Tue, 14 Oct 2014 13:48:08 +0000 http://www.hindawi.com/journals/bmri/2014/786084/ Citronella essential oil (CEO) has been reported as an excellent mosquito repellent; however, mild irritancy and rapid volatility limit its topical application. It was aimed to develop a nonirritant, stable, and consistent cream of CEO with improved residence time on skin using an industrial approach. Phase inversion temperature technique was employed to prepare the cream. It was optimized and characterized based on sensorial evaluation, emulsification, and consistency in terms of softness, greasiness, stickiness, and pH. The optimum batch (B5) was evaluated for viscosity (90249.67 ± 139.95 cP), texture profile with respect to firmness (38.67 ± 0.88 g), spreadability (70.33 ± 0.88 mJ), and extrudability (639.67 ± 8.09 ± 0.1 mJ) using texture analyzer along with two most popular marketed products selected as reference standard. Subsequently, B5 was found to be stable for more than 90 days and showed enhanced duration of mosquito repellency as compared to CEO. HS-GC ensured the intactness of CEO in B5. Investigated primary irritation index (PII 0.45) positioned B5 into the category of irritation barely perceptible. The pronounced texture profile and stability of B5 with extended residence time and less PII revealed its potential application in industry and offered a promising alternative to the marketed products of synthetic origin. Narayan Prasad Yadav, Vineet Kumar Rai, Nidhi Mishra, Priyam Sinha, Dnyaneshwar Umrao Bawankule, Anirban Pal, Arun Kumar Tripathi, and Chandan Singh Chanotiya Copyright © 2014 Narayan Prasad Yadav et al. All rights reserved. Serum-Free Medium Optimization Based on Trial Design and Support Vector Regression Tue, 14 Oct 2014 07:59:16 +0000 http://www.hindawi.com/journals/bmri/2014/269305/ The Plackett-Burman design and support vector machine (SVM) were reported to be used on many fields such as some feature selections, protein structure prediction, or forecasting of other situations. Here, with suspension adapted Chinese hamster ovary (CHO) cells as the object of study, a serum-free medium for the culture of CHO cells in suspension was optimized by this method. Support vector machine based on genetic algorithm was used to predict the growth rate of CHO and prove the results from the trial designs. Experimental results indicated that ZnSO4, transferrin, and bovine serum albumin (BSA) were important ones. The same conclusion was arrived at when the support vector regression model analyzed the experimental results. With the methods mentioned, the influence of 7 medium supplements on the growth of CHO cells in suspension was evaluated efficiently. Jian Xu, Fang-rong Yan, Zhi-hui Li, Deng Wang, Hai-lin Sheng, and Yu Liu Copyright © 2014 Jian Xu et al. All rights reserved. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy Tue, 14 Oct 2014 07:00:02 +0000 http://www.hindawi.com/journals/bmri/2014/530342/ Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals) were used in the study. The key words including “cancer”, “cell death”, “apoptosis”, “autophagy,” “necrosis,” and “Chinese medicine” were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future. Xuanbin Wang, Yibin Feng, Ning Wang, Fan Cheung, Hor Yue Tan, Sen Zhong, Charlie Li, and Seiichi Kobayashi Copyright © 2014 Xuanbin Wang et al. All rights reserved. H-CRRETAWAC-OH, a Lead Structure for the Development of Radiotracer Targeting Integrin α5β1? Mon, 13 Oct 2014 14:04:26 +0000 http://www.hindawi.com/journals/bmri/2014/243185/ Imaging of angiogenic processes is of great interest in preclinical research as well as in clinical settings. The most commonly addressed target structure for imaging angiogenesis is the integrin αvβ3. Here we describe the synthesis and evaluation of [18F]FProp--Arg-Arg-Glu-Thr-Ala-Trp-Ala--OH, a radiolabelled peptide designed to selectively target the integrin α5β1. Conjugation of 4-nitrophenyl-(RS)-2-[18F]fluoropropionate provided [18F]FProp--Arg-Arg-Glu-Thr-Ala-Trp-Ala--OH in high radiochemical purity (>95%) and a radiochemical yield of approx. 55%. In vitro evaluation showed α5β1 binding affinity in the nanomolar range, whereas affinity to αvβ3 and αIIbβ3 was >50 μM. Cell uptake studies using human melanoma M21 (αvβ3-positive and α5β1-negative), human melanoma M21-L (αvβ3-negative and α5β1-negative), and human prostate carcinoma DU145 (αvβ3-negative and α5β1-positive) confirmed receptor-specific binding. The radiotracer was stable in human serum and showed low protein binding. Biodistribution studies showed tumour uptake ranging from 2.5 to 3.5% ID/g between 30 and 120 min post-injection. However, blocking studies and studies using mice bearing α5β1-negative M21 tumours did not confirm receptor-specific uptake of [18F]FProp--Arg-Arg-Glu-Thr-Ala-Trp-Ala--OH, although this radiopeptide revealed high affinity and substantial selectivity to α5β1 in vitro. Further experiments are needed to study the in vivo metabolism of this peptide and to develop improved radiopeptide candidates suitable for PET imaging of α5β1 expression in vivo. Roland Haubner, Simone Maschauer, Jürgen Einsiedel, Iris E. Eder, Christine Rangger, Peter Gmeiner, Irene J. Virgolini, and Olaf Prante Copyright © 2014 Roland Haubner et al. All rights reserved. The Prognostic Impact of High On-Treatment Platelet Reactivity with Aspirin or ADP Receptor Antagonists: Systematic Review and Meta-Analysis Mon, 13 Oct 2014 07:55:07 +0000 http://www.hindawi.com/journals/bmri/2014/610296/ Objective. Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64–68) and 22.7% (22.4–27.8), of female gender. After a median follow-up of 1 year (0.1–1), cardiac adverse events occurred in 8.3% (3–11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], ). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89–1.22, 0%). Conclusions. After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed. Fabrizio D’Ascenzo, Umberto Barbero, Marta Bisi, Claudio Moretti, Pierluigi Omedè, Enrico Cerrato, Giorgio Quadri, Federico Conrotto, Giuseppe Biondi Zoccai, James J. DiNicolantonio, Mauro Gasparini, Sripal Bangalore, and Fiorenzo Gaita Copyright © 2014 Fabrizio D’Ascenzo et al. All rights reserved. Heat Shock Protein 90 in Alzheimer’s Disease Mon, 13 Oct 2014 07:15:56 +0000 http://www.hindawi.com/journals/bmri/2014/796869/ Alzheimer’s disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aβ) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response. In AD, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70. Therefore, we review here to further discuss the recent advances and challenges in targeting Hsp90 for AD therapy. Jiang-Rong Ou, Meng-Shan Tan, An-Mu Xie, Jin-Tai Yu, and Lan Tan Copyright © 2014 Jiang-Rong Ou et al. All rights reserved. Prognostic Implication of Predominant Histologic Subtypes of Lymph Node Metastases in Surgically Resected Lung Adenocarcinoma Sun, 12 Oct 2014 08:06:24 +0000 http://www.hindawi.com/journals/bmri/2014/645681/ The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) proposed a new classification for lung adenocarcinoma (AD) based on predominant histologic subtypes, such as lepidic, papillary, acinar, solid, and micropapillary; this system reportedly reflects well outcomes of patients with surgically resected lung AD. However, the prognostic implication of predominant histologic subtypes in lymph nodes metastases is unclear so far. In this study, we compared predominant subtypes between primary lung tumors and lymph node metastatic lesions in 24 patients with surgically treated lung adenocarcinoma with lymph node metastases. Additionally, we analyzed prognostic implications of these predominant histologic subtypes. We observed several discordance patterns between predominant subtypes in primary lung tumors and lymph node metastases. Concordance rates were 22%, 64%, and 100%, respectively, in papillary-, acinar-, and solid-predominant primary lung tumors. We observed that the predominant subtype in the primary lung tumor (HR 12.7, ), but not that in lymph node metastases (HR 0.18, ), determines outcomes in patients with surgically resected lung AD with lymph node metastases. Kenichi Suda, Katsuaki Sato, Shigeki Shimizu, Kenji Tomizawa, Toshiki Takemoto, Takuya Iwasaki, Masahiro Sakaguchi, and Tetsuya Mitsudomi Copyright © 2014 Kenichi Suda et al. All rights reserved. Freeze-Drying of Plant Tissue Containing HBV Surface Antigen for the Oral Vaccine against Hepatitis B Sun, 12 Oct 2014 07:20:35 +0000 http://www.hindawi.com/journals/bmri/2014/485689/ The aim of this study was to develop a freeze-drying protocol facilitating successful processing of plant material containing the small surface antigen of hepatitis B virus (S-HBsAg) while preserving its VLP structure and immunogenicity. Freeze-drying of the antigen in lettuce leaf tissue, without any isolation or purification step, was investigated. Each process step was consecutively evaluated and the best parameters were applied. Several drying profiles and excipients were tested. The profile of 20°C for 20 h for primary and 22°C for 2 h for secondary drying as well as sucrose expressed efficient stabilisation of S-HBsAg during freeze-drying. Freezing rate and postprocess residual moisture were also analysed as important factors affecting S-HBsAg preservation. The process was reproducible and provided a product with VLP content up to 200 µg/g DW. Assays for VLPs and total antigen together with animal immunisation trials confirmed preservation of antigenicity and immunogenicity of S-HBsAg in freeze-dried powder. Long-term stability tests revealed that the stored freeze-dried product was stable at 4°C for one year, but degraded at elevated temperatures. As a result, a basis for an efficient freeze-drying process has been established and a suitable semiproduct for oral plant-derived vaccine against HBV was obtained. Marcin Czyż, Radosław Dembczyński, Roman Marecik, Justyna Wojas-Turek, Magdalena Milczarek, Elżbieta Pajtasz-Piasecka, Joanna Wietrzyk, and Tomasz Pniewski Copyright © 2014 Marcin Czyż et al. All rights reserved. High Resolution Melting Analysis for Rapid Mutation Screening in Gyrase and Topoisomerase IV Genes in Quinolone-Resistant Salmonella enterica Sun, 12 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/718084/ The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM) assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR) of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (; S83F, S83Y, S83I, D87G, D87Y, and D87N) and parE (; M438I). Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC  μg/mL). Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes. Soo Tein Ngoi and Kwai Lin Thong Copyright © 2014 Soo Tein Ngoi and Kwai Lin Thong. All rights reserved. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile Sun, 21 Sep 2014 06:53:27 +0000 http://www.hindawi.com/journals/bmri/2014/683068/ Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. Karina Sánchez-Reyes, Alejandro Bravo-Cuellar, Georgina Hernández-Flores, José Manuel Lerma-Díaz, Luis Felipe Jave-Suárez, Paulina Gómez-Lomelí, Ruth de Celis, Adriana Aguilar-Lemarroy, Jorge Ramiro Domínguez-Rodríguez, and Pablo Cesar Ortiz-Lazareno Copyright © 2014 Karina Sánchez-Reyes et al. All rights reserved. Exercise Improves Immune Function, Antidepressive Response, and Sleep Quality in Patients with Chronic Primary Insomnia Sun, 21 Sep 2014 06:25:01 +0000 http://www.hindawi.com/journals/bmri/2014/498961/ The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm3) and CD8 (532.4 ± 259 to 435.7 ± 204 mm3). Decreases in cortisol were significantly correlated with increases in total sleep time and REM sleep . In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables. Giselle Soares Passos, Dalva Poyares, Marcos Gonçalves Santana, Alexandre Abílio de Souza Teixeira, Fábio Santos Lira, Shawn D. Youngstedt, Ronaldo Vagner Thomatieli dos Santos, Sergio Tufik, and Marco Túlio de Mello Copyright © 2014 Giselle Soares Passos et al. All rights reserved. From Pathways to Targets: Understanding the Mechanisms behind Polyglutamine Disease Sun, 21 Sep 2014 06:05:06 +0000 http://www.hindawi.com/journals/bmri/2014/701758/ The history of polyglutamine diseases dates back approximately 20 years to the discovery of a polyglutamine repeat in the androgen receptor of SBMA followed by the identification of similar expansion mutations in Huntington’s disease, SCA1, DRPLA, and the other spinocerebellar ataxias. This common molecular feature of polyglutamine diseases suggests shared mechanisms in disease pathology and neurodegeneration of disease specific brain regions. In this review, we discuss the main pathogenic pathways including proteolytic processing, nuclear shuttling and aggregation, mitochondrial dysfunction, and clearance of misfolded polyglutamine proteins and point out possible targets for treatment. Jonasz Jeremiasz Weber, Anna Sergeevna Sowa, Tina Binder, and Jeannette Hübener Copyright © 2014 Jonasz Jeremiasz Weber et al. All rights reserved. Erratum to “A Bioinformatics Pipeline for the Analyses of Viral Escape Dynamics and Host Immune Responses during an Infection” Sun, 21 Sep 2014 06:02:49 +0000 http://www.hindawi.com/journals/bmri/2014/680249/ Preston Leung, Rowena Bull, Andrew Lloyd, and Fabio Luciani Copyright © 2014 Preston Leung et al. All rights reserved. Protective Role of 5-Lipoxigenase during Leishmania infantum Infection Is Associated with Th17 Subset Sun, 21 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/264270/ Visceral leishmaniasis (VL) is a chronic and fatal disease caused by Leishmania infantum in Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Leucotriens are lipid mediators synthesized by 5-lipoxygenase (5-LO) and they display a protective role against protozoan parasites by inducing several functions in leucocytes. We determined the role of 5-LO activity in parasite control, focusing on the inflammatory immune response against Leishmania infantum infection. LTB4 is released during in vitro infection. The genetic ablation of 5-LO promoted susceptibility in highly resistant mice strains, harboring more parasites into target organs. The susceptibility was related to the failure of neutrophil migration to the infectious foci. Investigating the neutrophil failure, there was a reduction of proinflammatory cytokines involved in the related Th17 axis released into the organs. Genetic ablation of 5-LO reduced the CD4+T cells producing IL-17, without interfering in Th1 subset. L. infantum failed to activate DC from , showing reduced surface costimulatory molecule expression and proinflammatory cytokines involved in Th17 differentiation. BLT1 blockage with selective antagonist interferes with DC maturation and proinflammatory cytokines release. Thus, 5-LO activation coordinates the inflammatory immune response involved in the control of VL. Laís Amorim Sacramento, Fernando Q. Cunha, Roque Pacheco de Almeida, João Santana da Silva, and Vanessa Carregaro Copyright © 2014 Laís Amorim Sacramento et al. All rights reserved. Differential Protein Network Analysis of the Immune Cell Lineage Sun, 21 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/363408/ Recently, the Immunological Genome Project (ImmGen) completed the first phase of the goal to understand the molecular circuitry underlying the immune cell lineage in mice. That milestone resulted in the creation of the most comprehensive collection of gene expression profiles in the immune cell lineage in any model organism of human disease. There is now a requisite to examine this resource using bioinformatics integration with other molecular information, with the aim of gaining deeper insights into the underlying processes that characterize this immune cell lineage. We present here a bioinformatics approach to study differential protein interaction mechanisms across the entire immune cell lineage, achieved using affinity propagation applied to a protein interaction network similarity matrix. We demonstrate that the integration of protein interaction networks with the most comprehensive database of gene expression profiles of the immune cells can be used to generate hypotheses into the underlying mechanisms governing the differentiation and the differential functional activity across the immune cell lineage. This approach may not only serve as a hypothesis engine to derive understanding of differentiation and mechanisms across the immune cell lineage, but also help identify possible immune lineage specific and common lineage mechanism in the cells protein networks. Trevor Clancy and Eivind Hovig Copyright © 2014 Trevor Clancy and Eivind Hovig. All rights reserved.