BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. EULAR Task Force Recommendations on Annual Cardiovascular Risk Assessment for Patients with Rheumatoid Arthritis: An Audit of the Success of Implementation in a Rheumatology Outpatient Clinic Sun, 01 Mar 2015 11:23:04 +0000 Objective. EULAR recommendations for cardiovascular disease (CVD) risk management include annual CVD risk assessments for patients with rheumatoid arthritis (RA). We evaluated the recording of CVD risk factors (CVD-RF) in a rheumatology outpatient clinic, where EULAR recommendations had been implemented. Further, we compared CVD-RF recordings between a regular rheumatology outpatient clinic (RegROC) and a structured arthritis clinic (AC). Methods. In 2012, 1142 RA patients visited the rheumatology outpatient clinic: 612 attended RegROC and 530 attended AC. We conducted a search in the patient journals to ascertain the rate of CVD-RF recording. Results. The overall CVD-RF recording rate was 40.1% in the rheumatology outpatient clinic, reflecting a recording rate of 59.1% in the AC and 23.6% in the RegROC. The odds ratios for having CVD-RFs recorded for patients attending AC compared to RegROC were as follows: blood pressure: 12.4, lipids: 5.0-6.0, glucose: 9.1, HbA1c: 6.1, smoking: 1.4, and for having all the CVD-RFs needed to calculate the CVD risk by the systematic coronary risk evaluation (SCORE): 21.0. Conclusion. The CVD-RF recording rate was low in a rheumatology outpatient clinic. However, a systematic team-based model was superior compared to a RegROC. Further measures are warranted to improve CVD-RF recording in RA patients. Eirik Ikdahl, Silvia Rollefstad, Inge C. Olsen, Tore K. Kvien, Inger Johanne Widding Hansen, Dag Magnar Soldal, Glenn Haugeberg, and Anne Grete Semb Copyright © 2015 Eirik Ikdahl et al. All rights reserved. Analysis of Monocytic and Granulocytic Myeloid-Derived Suppressor Cells Subsets in Patients with Hepatitis C Virus Infection and Their Clinical Significance Sun, 01 Mar 2015 11:17:57 +0000 Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+ cells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z = −2.438, P = 0.015), while there was no statistical difference between the frequency of CD33+CD11b+CD15+ (G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z = −2.685, P = 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree. Gang Ning, Lanhui She, Lirong Lu, Ying Liu, Yingfu Zeng, Ying Yan, and Chaoshuang Lin Copyright © 2015 Gang Ning et al. All rights reserved. Ascorbic Acid, Ultraviolet C Rays, and Glucose but not Hyperthermia Are Elicitors of Human β-Defensin 1 mRNA in Normal Keratinocytes Sun, 01 Mar 2015 10:06:07 +0000 Hosts’ innate defense systems are upregulated by antimicrobial peptide elicitors (APEs). Our aim was to investigate the effects of hyperthermia, ultraviolet A rays (UVA), and ultraviolet C rays (UVC) as well as glucose and ascorbic acid (AA) on the regulation of human β-defensin 1 (DEFB1), cathelicidin (CAMP), and interferon-γ (IFNG) genes in normal human keratinocytes (NHK). The indirect in vitro antimicrobial activity against Staphylococcus aureus and Listeria monocytogenes of these potential APEs was tested. We found that AA is a more potent APE for DEFB1 than glucose in NHK. Glucose but not AA is an APE for CAMP. Mild hypo- (35°C) and hyperthermia (39°C) are not APEs in NHK. AA-dependent DEFB1 upregulation below 20 mM predicts in vitro antimicrobial activity as well as glucose- and AA-dependent CAMP and IFNG upregulation. UVC upregulates CAMP and DEFB1 genes but UVA only upregulates the DEFB1 gene. UVC is a previously unrecognized APE in human cells. Our results suggest that glucose upregulates CAMP in an IFN-γ-independent manner. AA is an elicitor of innate immunity that will challenge the current concept of late activation of adaptive immunity of this vitamin. These results could be useful in designing new potential drugs and devices to combat skin infections. Luis Antonio Cruz Díaz, María Guadalupe Flores Miramontes, Paulina Chávez Hurtado, Kirk Allen, Marisela Gonzalez Ávila, and Ernesto Prado Montes de Oca Copyright © 2015 Luis Antonio Cruz Díaz et al. All rights reserved. Plant Antimicrobial Peptides as Potential Anticancer Agents Sun, 01 Mar 2015 09:57:02 +0000 Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy. Jaquelina Julia Guzmán-Rodríguez, Alejandra Ochoa-Zarzosa, Rodolfo López-Gómez, and Joel E. López-Meza Copyright © 2015 Jaquelina Julia Guzmán-Rodríguez et al. All rights reserved. Temozolomide and Radiotherapy versus Radiotherapy Alone in High Grade Gliomas: A Very Long Term Comparative Study and Literature Review Sun, 01 Mar 2015 09:55:03 +0000 Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ. Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ. Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11. Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis. Salvatore Parisi, Pietro Corsa, Arcangela Raguso, Antonio Perrone, Sabrina Cossa, Tindara Munafò, Gerardo Sanpaolo, Elisa Donno, Maria Antonietta Clemente, Michele Piombino, Federico Parisi, and Guido Valle Copyright © 2015 Salvatore Parisi et al. All rights reserved. Genetic and Metabolic Intraspecific Biodiversity of Ganoderma lucidum Sun, 01 Mar 2015 09:27:30 +0000 Fourteen Ganoderma lucidum strains from different geographic regions were identified using ITS region sequencing. Based on the sequences obtained, the genomic relationship between the analyzed strains was determined. All G. lucidum strains were also genetically characterized using the AFLP technique. G. lucidum strains included in the analysis displayed an AFLP profile similarity level in the range from 9.6 to 33.9%. Biolog FF MicroPlates were applied to obtain data on utilization of 95 carbon sources and mitochondrial activity. The analysis allowed comparison of functional diversity of the fungal strains. The substrate utilization profiles for the isolates tested revealed a broad variability within the analyzed G. lucidum species and proved to be a good profiling technology for studying the diversity in fungi. Significant differences have been demonstrated in substrate richness values. Interestingly, the analysis of growth and biomass production also differentiated the strains based on the growth rate on the agar and sawdust substrate. In general, the mycelial growth on the sawdust substrate was more balanced and the fastest fungal growth was observed for GRE3 and FCL192. Anna Pawlik, Grzegorz Janusz, Iwona Dębska, Marek Siwulski, Magdalena Frąc, and Jerzy Rogalski Copyright © 2015 Anna Pawlik et al. All rights reserved. Regulation of miRNAs Affects Radiobiological Response of Lung Cancer Stem Cells Sun, 01 Mar 2015 09:09:18 +0000 Radiotherapy (RT) is a key therapeutic strategy for lung cancer, the most common cause of cancer-related deaths worldwide, but radioresistance often occurs and leads to failure of RT. It is therefore important to clarify the mechanism underlying radioresistance in lung cancer. Cancer stem cells (CSCs) are considered the fundamental reason for radioresistance. MicroRNAs (miRNAs) have been regarded as important regulatory molecules of CSCs, carcinogenesis, and treatment response of cancers. It is crucial to clarify how regulation of miRNAs affects repair of DNA damage, redistribution, repopulation, reoxygenation, and radiosensitivity (5R) of lung cancer stem cells (LCSCs). A thorough understanding of the regulation of miRNAs affecting 5R of LCSCs has potential impact on identifying novel targets and thus may improve the efficacy of lung cancer radiotherapy. Yan-mei Xu, Xing-yun Liao, Xie-wan Chen, De-zhi Li, Jian-guo Sun, and Rong-xia Liao Copyright © 2015 Yan-mei Xu et al. All rights reserved. Increased Incidence of Atrial Fibrillation in Patients with Rheumatoid Arthritis Sun, 01 Mar 2015 08:48:04 +0000 Objective. To investigate the incidence of atrial fibrillation (AF) among patients with rheumatoid arthritis (RA) compared to the general population. Methods. A population-based inception cohort of Olmsted County, Minnesota, residents with incident RA in 1980–2007 and a cohort of non-RA subjects from the same population base were assembled and followed until 12/31/2008. The occurrence of AF was ascertained by medical record review. Results. The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 (SD:15.7) years, 68% women in both cohorts). The prevalence of AF was similar in the RA and non-RA cohorts at RA incidence/index date (4% versus 3%; ). The cumulative incidence of AF during follow-up was higher among patients with RA compared to non-RA subjects (18.3% versus 16.3% at 20 years; ). This difference persisted after adjustment for age, sex, calendar year, smoking, and hypertension (hazard ratio: 1.46; 95% CI: 1.07, 2.00). There was no evidence of a differential impact of AF on mortality in patients with RA compared to non-RA subjects (hazard ratio 2.5 versus 2.8; interaction ). Conclusion. The incidence of AF is increased in patients with RA, even after adjustment for AF risk factors. AF related mortality risk did not differ between patients with and without RA. A. Kirstin Bacani, Cynthia S. Crowson, Véronique L. Roger, Sherine E. Gabriel, and Eric L. Matteson Copyright © 2015 A. Kirstin Bacani et al. All rights reserved. Effect of Recombinant Prophenin 2 on the Integrity and Viability of Trichomonas vaginalis Sun, 01 Mar 2015 08:12:34 +0000 Trichomonas vaginalis is the causal agent of trichomoniasis, which is associated with preterm child delivery, low birth weight, and an increased risk of infection by human papilloma virus and human immunodeficiency virus following exposure. Several reports have established increasing numbers of trichomoniasis cases resistant to metronidazole, the agent used for treatment, and it is therefore important to identify new therapeutic alternatives. Previously, our group reported the effect of tritrpticin, a synthetic peptide derived from porcine prophenin, on T. vaginalis; however, the hemolytic activity of this small peptide complicates its possible use as a therapeutic agent. In this study, we report that the propeptide and the processed peptide of prophenin 2 (cleaved with hydroxylamine) affected the integrity and growth of T. vaginalis and that pro-prophenin 2 displays some resistance to proteolysis by T. vaginalis proteinases at 1 h. Its effect on T. vaginalis as well as its low hemolytic activity and short-time stability to parasite proteinases makes prophenin 2 an interesting candidate for synergistic or alternative treatment against T. vaginalis. J. L. Hernandez-Flores, M. C. Rodriguez, A. Gastelum Arellanez, A. Alvarez-Morales, and E. E. Avila Copyright © 2015 J. L. Hernandez-Flores et al. All rights reserved. Chronic Ingestion of High Dosed Phikud Navakot Extraction Induces Mesangiolysis in Rats with Alteration of AQP1 and Hsp60 Expressions Sun, 01 Mar 2015 07:53:04 +0000 Phikud Navakot (PN) is commonly used in Thai traditional medicine for alleviation of cardiovascular and cerebrovascular symptoms; however little is known about the chronic toxicity effects of the extracts from the herbs in PN. Repeated extraction doses of 10, 100, and 1,000 mg/kg/day were randomly administered to both male and female Sprague Dawley rats for 12 months. Histopathological study revealed that mesangiolysis was predominately found at the highest dose. Aquaporin 1 (AQP1) expression in the mesangiolytic glomeruli was significantly lower than in the intact glomeruli. This may be relevant to an imbalance of vascular function manifested by AQP1 alteration. In the mesangiolytic glomeruli, 60 kDa heat shock protein (Hsp60) was significantly upregulated on the endothelial lining cells of aneurysm and vascular cyst. Hsp60 increase may be related to endothelial cell damage due to its intracellular protective role. Blood urea nitrogen and creatinine levels remained within their normal range indicating well-functioning renal reserve function. In conclusion, high dosed PN may affect the endothelium leading to inability of vascular permeability and consequence to mesangiolysis. Our results suggest that only a high dose of chronic oral administration of PN is relatively toxic in association with mesangiolysis. The NOAEL was determined to be 100 mg/kg/day. Kanchana Kengkoom and Sumate Ampawong Copyright © 2015 Kanchana Kengkoom and Sumate Ampawong. All rights reserved. MicroRNA-146b-3p Regulates Retinal Inflammation by Suppressing Adenosine Deaminase-2 in Diabetes Sun, 01 Mar 2015 07:30:25 +0000 Hyperglycemia- (HG-) Amadori-glycated albumin- (AGA-) induced activation of microglia and monocytes and their adherence to retinal vascular endothelial cells contribute to retinal inflammation leading to diabetic retinopathy (DR). There is a great need for early detection of DR before demonstrable tissue damages become irreversible. Extracellular adenosine, required for endogenous anti-inflammation, is regulated by the interplay of equilibrative nucleoside transporter with adenosine deaminase (ADA) and adenosine kinase. ADA, including ADA1 and ADA2, exists in all organisms. However, because ADA2 gene has not been identified in mouse genome, how diabetes alters adenosine-dependent anti-inflammation remains unclear. Studies of pig retinal microglia and human macrophages revealed a causal role of ADA2 in inflammation. Database search suggested miR-146b-3p recognition sites in the 3′-UTR of ADA2 mRNA. Coexpression of miR-146b-3p, but not miR-146-5p or nontargeting miRNA, with 3′-UTR of the ADA2 gene was necessary to suppress a linked reporter gene. In the vitreous of diabetic patients, decreased miR-146b-3p is associated with increased ADA2 activity. Ectopic expression of miR-146b-3p suppressed ADA2 expression, activity, and TNF-α release in the AGA-treated human macrophages. These results suggest a regulatory role of miR-146b-3p in diabetes related retinal inflammation by suppressing ADA2. Sadanand Fulzele, Ahmed El-Sherbini, Saif Ahmad, Rajnikumar Sangani, Suraporn Matragoon, Azza El-Remessy, Reshmitha Radhakrishnan, and Gregory I. Liou Copyright © 2015 Sadanand Fulzele et al. All rights reserved. A Novel Rat Model of Vitamin D Deficiency: Safe and Rapid Induction of Vitamin D and Calcitriol Deficiency without Hyperparathyroidism Sat, 28 Feb 2015 11:48:29 +0000 Vitamin D deficiency is associated with a range of clinical disorders. To study the mechanisms involved and improve treatments, animal models are tremendously useful. Current vitamin D deficient rat models have important practical limitations, including time requirements when using, exclusively, a vitamin D deficient diet. More importantly, induction of hypovitaminosis D causes significant fluctuations in parathyroid hormone (PTH) and mineral levels, complicating the interpretation of study results. To overcome these shortcomings, we report the successful induction of vitamin D deficiency within three weeks, with stable serum PTH and minerals levels, in Wistar rats. We incorporated two additional manoeuvres compared to a conventional diet. Firstly, the vitamin D depleted diet is calcium (Ca) enriched, to attenuate the development of secondary hyperparathyroidism. Secondly, six intraperitoneal injections of paricalcitol during the first two weeks are given to induce the rapid degradation of circulating vitamin D metabolites. After three weeks, serum 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) levels had dropped below detection limits, with unchanged serum PTH, Ca, and phosphate (P) levels. Therefore, this model provides a useful tool to examine the sole effect of hypovitaminosis D, in a wide range of research settings, without confounding changes in PTH, Ca, and P. Andrea W. D. Stavenuiter, Maria Vittoria Arcidiacono, Evelina Ferrantelli, Eelco D. Keuning, Marc Vila Cuenca, Piet M. ter Wee, Robert H. J. Beelen, Marc G. Vervloet, and Adriana S. Dusso Copyright © 2015 Andrea W. D. Stavenuiter et al. All rights reserved. Vitamin Supplementation as Possible Prophylactic Treatment against Migraine with Aura and Menstrual Migraine Sat, 28 Feb 2015 11:04:48 +0000 Migraine is the most common form of headache disorder globally. The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine or an increase in homocysteine levels can lead to migraine attacks; therefore, vitamins could play a vital role in migraine prevention. For instance, riboflavin influences mitochondrial dysfunction and prevents migraine. Genes such as flavoenzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma levels of homocysteine and migraine with aura. Homocysteine catalyzation requires the presence of vitamins B6, B12, and folic acid, which can decrease the severity of migraine with aura, making these vitamins potentially useful prophylactic agents for treating migraine with aura. Menstrual migraine, on the other hand, is associated with increased prostaglandin (PG) levels in the endometrium, indicating a role for vitamin E, which is an anti-PG. Vitamin C can also be used as a scavenger of reactive oxygen species for treating neurogenic inflammation in migraine patients. This paper reviews possible therapies based on vitamin supplementation for migraine prophylaxis, focusing on migraine with aura and menstrual migraine. Munvar Miya Shaik and Siew Hua Gan Copyright © 2015 Munvar Miya Shaik and Siew Hua Gan. All rights reserved. Predicting the Functions of Long Noncoding RNAs Using RNA-Seq Based on Bayesian Network Sat, 28 Feb 2015 07:50:45 +0000 Long noncoding RNAs (lncRNAs) have been shown to play key roles in various biological processes. However, functions of most lncRNAs are poorly characterized. Here, we represent a framework to predict functions of lncRNAs through construction of a regulatory network between lncRNAs and protein-coding genes. Using RNA-seq data, the transcript profiles of lncRNAs and protein-coding genes are constructed. Using the Bayesian network method, a regulatory network, which implies dependency relations between lncRNAs and protein-coding genes, was built. In combining protein interaction network, highly connected coding genes linked by a given lncRNA were subsequently used to predict functions of the lncRNA through functional enrichment. Application of our method to prostate RNA-seq data showed that 762 lncRNAs in the constructed regulatory network were assigned functions. We found that lncRNAs are involved in diverse biological processes, such as tissue development or embryo development (e.g., nervous system development and mesoderm development). By comparison with functions inferred using the neighboring gene-based method and functions determined using lncRNA knockdown experiments, our method can provide comparable predicted functions of lncRNAs. Overall, our method can be applied to emerging RNA-seq data, which will help researchers identify complex relations between lncRNAs and coding genes and reveal important functions of lncRNAs. Yun Xiao, Yanling Lv, Hongying Zhao, Yonghui Gong, Jing Hu, Feng Li, Jinyuan Xu, Jing Bai, Fulong Yu, and Xia Li Copyright © 2015 Yun Xiao et al. All rights reserved. Hematopoietic Cancer Cell Lines Can Support Replication of Sabin Poliovirus Type 1 Sat, 28 Feb 2015 07:49:41 +0000 Viral vaccines can be produced in adherent or in suspension cells. The objective of this work was to screen human suspension cell lines for the capacity to support viral replication. As the first step, it was investigated whether poliovirus can replicate in such cell lines. Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937. Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication. Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155. Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection. Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4. Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant. Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus. Dinja Oosterhoff, Gerard van de Weerd, Gerco van Eikenhorst, Tanja D. de Gruijl, Leo A. van der Pol, and Wilfried A. M. Bakker Copyright © 2015 Dinja Oosterhoff et al. All rights reserved. Association of IL-6 Polymorphism -174G/C and Metabolic Syndrome in Hypertensive Patients Sat, 28 Feb 2015 07:10:53 +0000 Introduction. Visceral obesity, the central core of metabolic syndrome (MetS), is conceived as the pathogenic basis of an increased cardiovascular burden and is related with changes in cytokines. We investigated whether IL-6-174G/C gene polymorphism is associated with MetS prevalence in hypertensive patients. Method. A population of hypertensive patients was included and stratified by the presence of MetS according to IDF criteria and evaluated by Framingham risk score. The IL-6-174G/C genotyping was performed by polymerase chain reaction and the prevalence of MetS was compared between “C” carrier and “non-C” carrier groups. Results. From an original sample of 664 patients, 612 (34.2% men, age 57.3 ± 10.1, 30.4% diabetics) were included. MetS was diagnosed in 51.3% of total population and “C” carriers demonstrated high prevalence of MetS () and each of its components. On binary logistic regression, it was observed that the IL-6 polymorphism was independently associated with occurrence of MetS, even after adjusting for covariates (OR 1.13–2.37, 95% CI, ). Conclusion. The C allele at the -174 locus of IL-6 gene is independently associated with the occurrence of metabolic syndrome, emphasizing the importance of inflammatory genetic background in the pathogenesis of visceral obesity and related cardiovascular burden. Andrei Alkmim Teixeira, Beata Marie Redublo Quinto, Maria Aparecida Dalboni, Cassio Jose de Oliveira Rodrigues, and Marcelo Costa Batista Copyright © 2015 Andrei Alkmim Teixeira et al. All rights reserved. Genome-Wide Identification, Evolutionary, and Expression Analyses of Histone H3 Variants in Plants Thu, 26 Feb 2015 12:48:15 +0000 Histone variants alter the nucleosome structure and play important roles in chromosome segregation, transcription, DNA repair, and sperm compaction. Histone H3 is encoded by many genes in most eukaryotic species and is the histone that contains the largest variety of posttranslational modifications. Compared with the metazoan H3 variants, little is known about the complex evolutionary history of H3 variants proteins in plants. Here, we study the identification, evolutionary, and expression analyses of histone H3 variants from genomes in major branches in the plant tree of life. Firstly we identified all the histone three related (HTR) genes from the examined genomes, then we classified the four groups variants: centromeric H3, H3.1, H3.3 and H3-like, by phylogenetic analysis, intron information, and alignment. We further demonstrated that the H3 variants have evolved under strong purifying selection, indicating the conservation of HTR proteins. Expression analysis revealed that the HTR has a wide expression profile in maize and rice development and plays important roles in development. Jinteng Cui, Zhanlu Zhang, Yang Shao, Kezhong Zhang, Pingsheng Leng, and Zhe Liang Copyright © 2015 Jinteng Cui et al. All rights reserved. Evolution of Action Potential Alternans in Rabbit Heart during Acute Regional Ischemia Thu, 26 Feb 2015 12:12:10 +0000 This study investigates the development of the spatiotemporal pattern of action potential alternans during acute regional ischemia. Experiments were carried out in isolated Langendorff-perfused rabbit heart using a combination of optical mapping and microelectrode recordings. The alternans pattern significantly changed over time and had a biphasic character reaching maximum at 6–9 min after occlusion. Phase I (3–11 minutes of ischemia) is characterized by rapid increase in the alternans magnitude and expansion of the alternans territory. Phase I is followed by gradual decline of alternans (Phase II) in both magnitude and territory. During both phases we observed significant beat-to-beat variations of the optical action potential amplitude (OAPA) alternans. Simultaneous microelectrode recordings from subepicardial and subendocardial layers showed that OAPA alternans coincided with intramural 2 : 1 conduction blocks. Our findings are consistent with the modeling studies predicting that during acute regional ischemia alternans can be driven by 2 : 1 conduction blocks in the ischemic region. Irma Martišienė, Jonas Jurevičius, Rūta Vosyliūtė, Antanas Navalinskas, Rimantas Treinys, Regina Mačianskienė, Rimantas Benetis, Arvydas Matiukas, and Arkady M. Pertsov Copyright © 2015 Irma Martišienė et al. All rights reserved. The Role of Cingulate Cortex in Vicarious Pain Thu, 26 Feb 2015 11:37:16 +0000 Vicarious pain is defined as the observation of individuals in pain. There is growing neuroimaging evidence suggesting that the cingulate cortex plays a significant role in self-experienced pain processing. Yet, very few studies have directly tested the distinct functions of the cingulate cortex for vicarious pain. In this review, one EEG and eighteen neuroimaging studies reporting cingulate cortex activity during pain observation were discussed. The data indicate that there is overlapping neural activity in the cingulate cortex during self- and vicarious pain. Such activity may contribute to shared neural pain representations that permit inference of the affective state of individuals in pain, facilitating empathy. However, the exact location of neuronal populations in which activity overlaps or differs for self- and observed pain processing requires further confirmation. This review also discusses evidence suggesting differential functions of the cingulate cortex in cognitive, affective, and motor processing during empathy induction. While affective processing in the cingulate cortex during pain observation has been explored relatively more often, its attention and motor roles remain underresearched. Shedding light on the neural correlates of vicarious pain and corresponding empathy in healthy populations can provide neurobiological markers and intervention targets for empathic deficits found in various clinical disorders. Esther H. Yesudas and Tatia M. C. Lee Copyright © 2015 Esther H. Yesudas and Tatia M. C. Lee. All rights reserved. Generation of Neurospheres from Human Adipose-Derived Stem Cells Thu, 26 Feb 2015 11:28:37 +0000 Transplantation of neural stem cells (NSCs) to treat neurodegenerative disease shows promise; however, the clinical application of NSCs is limited by the invasive procurement and ethical concerns. Adipose-derived stem cells (ADSCs) are a source of multipotent stem cells that can self-renew and differentiate into various kinds of cells; this study intends to generate neurospheres from human ADSCs by culturing ADSCs on uncoated culture flasks in serum-free neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF); the ADSCs-derived neurospheres were terminally differentiated after growth factor withdrawal. Expression of Nestin, NeuN, MAP2, and GFAP in ADSCs and terminally differentiated neurospheres was shown by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry; cell proliferation in neurospheres was evaluated by cell cycle analyses, immunostaining, and flow cytometry. These data strongly support the conclusion that human ADSCs can successfully differentiate into neurospheres efficiently on uncoated culture flasks, which present similar molecular marker pattern and proliferative ability with NSCs derived from embryonic and adult brain tissues. Therefore, human ADSCs may be an ideal alternative source of stem cells for the treatment of neurodegenerative diseases. Erfang Yang, Na Liu, Yingxin Tang, Yang Hu, Ping Zhang, Chao Pan, Shasha Dong, Youping Zhang, and Zhouping Tang Copyright © 2015 Erfang Yang et al. All rights reserved. Effect of Luteolin and Apigenin on the Expression of Oct-4, Sox2, and c-Myc in Dental Pulp Cells with In Vitro Culture Thu, 26 Feb 2015 11:25:09 +0000 Introduction. Dental pulp cells (DPCs) are promising cell source for dental tissue regeneration. Recently, small molecules which optimize microenvironment or activate the reprogramming network provide a new way to enhance the pluripotency. Two promising bioflavonoids luteolin and apigenin were reported to enhance reprogramming efficiency in mouse embryonic fibroblast (MEF). However, their effect and underlying mechanism in cell fate determination of human DPCs remain unclear. Methods. To elucidate the effect of luteolin and apigenin on the cell fate determination of DPCs, we explored the cell proliferation, cell cycle, senescence, apoptosis, expression of pluripotency markers Oct-4, Sox2, and c-Myc, and multilineage differentiation capability of DPCs with luteolin or apigenin treatment. Results. We demonstrated that luteolin and apigenin inhibited cell proliferation, arrested DPCs in G2/M and S phase, and upregulated PI value and apoptosis. Moreover, luteolin and apigenin increased telomerase activity, maintained DPCs in a presenescent state, and activated the expression of Oct-4, Sox2, and c-Myc at a dose- and time-dependent pattern in DPCs even at late passages, albeit repressed lineage-specific differentiation. Conclusions. Addition of luteolin and apigenin in the culture medium might provide an effective way to maintain DPCs in an undifferentiated stage and inhibit lineage-specific differentiation. Lu Liu, Zhengjun Peng, Zezhen Xu, and Xi Wei Copyright © 2015 Lu Liu et al. All rights reserved. Lutein Has a Protective Effect on Hepatotoxicity Induced by Arsenic via Nrf2 Signaling Thu, 26 Feb 2015 06:00:34 +0000 Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy. Shugang Li, Yusong Ding, Qiang Niu, Shangzhi Xu, Lijuan Pang, Rulin Ma, Mingxia Jing, Gangling Feng, Jing Xia Tang, Qian Zhang, Xiaomei Ma, Yizhong Yan, Jingyu Zhang, Meng Wei, Hai Xia Wang, Feng Li, and Shuxia Guo Copyright © 2015 Shugang Li et al. All rights reserved. Prediction of Outcome for Transabdominal Cerclage in Women with Cervical Insufficiency Wed, 25 Feb 2015 16:09:45 +0000 We investigated pregnancy outcome following transabdominal cerclage (TAC) in women with cervical insufficiency (CI) and explored parameters for predicting pregnancy outcomes following TAC. In this retrospective cohort study, we included 161 women with TAC. We considered demographic, obstetric, and gynecologic histories, pre- and postoperative cervical length (CL), and CL at 20–24 weeks as parameters for predicting outcomes following TAC. Univariate and multivariate analyses were used to identify risk factors for predicting delivery before 34 weeks after TAC. 182 pregnancies occurred after TAC, and 290 pregnancies prior to TAC were identified. The rate of delivery <34 weeks significantly decreased following TAC (5% versus 82%, ). Univariate analysis demonstrated that a short CL (<25 mm) at 20–24 weeks and adenomyosis were associated with delivery at <34 weeks’ gestation following TAC ( and , resp.). However, multivariate analysis demonstrated that only a short CL (<25 mm) at 20–24 weeks was a significant predictor (). TAC is an efficacious procedure that prolongs pregnancy in women with CI. A short CL at 20–24 weeks may predict the delivery at <34 weeks’ gestation following TAC. Ji Eun Song, Keun Young Lee, and Ga Hyun Son Copyright © 2015 Ji Eun Song et al. All rights reserved. Associations of LIG4 and HSPB1 Genetic Polymorphisms with Risk of Radiation-Induced Lung Injury in Lung Cancer Patients Treated with Radiotherapy Wed, 25 Feb 2015 13:54:15 +0000 Objective. This study aims to explore the correlations of genetic polymorphisms in LIG4 and HSPB1 genes with the radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), in lung cancer patients. Methods. A total of 160 lung cancer patients, who were diagnosed with inoperable lung cancer and received radiotherapy, were included in the present study from September 2009 to December 2011. TaqMan Real-Time PCR (RT-PCR) was used to verify the SNPs of LIG4 and HSPB1 genes. Chi-square criterion was used to compare the differences in demographic characteristics, exposure to risk factors, and SNPs genotypes. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by logistic regression analysis. All statistical analyses were conducted in SPSS 18.0. Results. A total of 32 (20.0%) lung cancer patients had RP after receiving radiotherapy. Of the 32 cases, 4 cases were of grade 2, 24 cases were of grade 3, and 4 cases were of grade 4. However, our results indicated that the general condition and treatment of all patients had no significant difference with RP risk . Meanwhile, our results revealed that there was no significant association between the frequencies of LIG4 rs1805388 and HSPB1 rs2868371 genotype distribution and the risk of RP . Conclusion. In conclusion, we demonstrated that the genetic polymorphisms in LIG4 rs1805388 and HSPB1 rs2868371 were not obviously correlated with the risk of RP and RILI of lung cancer. Feng Xu, Ji-Chang Han, Ya-Jun Zhang, Yi-Jie Zhang, Xiao-Chun Liu, Guan-Bin Qi, Dan Liu, Yan-Zhi Chen, Yu-Xia Zhao, and Lu Bai Copyright © 2015 Feng Xu et al. All rights reserved. ProGeRF: Proteome and Genome Repeat Finder Utilizing a Fast Parallel Hash Function Wed, 25 Feb 2015 13:26:55 +0000 Repetitive element sequences are adjacent, repeating patterns, also called motifs, and can be of different lengths; repetitions can involve their exact or approximate copies. They have been widely used as molecular markers in population biology. Given the sizes of sequenced genomes, various bioinformatics tools have been developed for the extraction of repetitive elements from DNA sequences. However, currently available tools do not provide options for identifying repetitive elements in the genome or proteome, displaying a user-friendly web interface, and performing-exhaustive searches. ProGeRF is a web site for extracting repetitive regions from genome and proteome sequences. It was designed to be efficient, fast, and accurate and primarily user-friendly web tool allowing many ways to view and analyse the results. ProGeRF (Proteome and Genome Repeat Finder) is freely available as a stand-alone program, from which the users can download the source code, and as a web tool. It was developed using the hash table approach to extract perfect and imperfect repetitive regions in a (multi)FASTA file, while allowing a linear time complexity. Robson da Silva Lopes, Walas Jhony Lopes Moraes, Thiago de Souza Rodrigues, and Daniella Castanheira Bartholomeu Copyright © 2015 Robson da Silva Lopes et al. All rights reserved. Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment Wed, 25 Feb 2015 12:17:23 +0000 Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents—doxorubicin and cisplatin—is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients’ survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients’ response to TACE treatment in liver cancer. Medhat S. El-Halawany, Heba M. Ismail, Ahmed A. Zeeneldin, Ammar Elfiky, Marwa Tantawy, Mohamed H. Kobaisi, Ikram Hamed, and Abdel Hady A. Abdel Wahab Copyright © 2015 Medhat S. El-Halawany et al. All rights reserved. Quantitative Analysis of Lung Ultrasonography for the Detection of Community-Acquired Pneumonia: A Pilot Study Wed, 25 Feb 2015 10:51:29 +0000 Background and Objective. Chest X-ray is recommended for routine use in patients with suspected pneumonia, but its use in emergency settings is limited. In this study, the diagnostic performance of a new method for quantitative analysis of lung ultrasonography was compared with bedside chest X-ray and visual lung ultrasonography for detection of community-acquired pneumonia, using thoracic computed tomography as a gold standard. Methods. Thirty-two spontaneously breathing patients with suspected community-acquired pneumonia, undergoing computed tomography examination, were consecutively enrolled. Each hemithorax was evaluated for the presence or absence of abnormalities by chest X-ray and quantitative or visual ultrasonography. Results. Quantitative ultrasonography showed higher sensitivity (93%), specificity (95%), and diagnostic accuracy (94%) than chest X-ray (64%, 80%, and 69%, resp.), visual ultrasonography (68%, 95%, and 77%, resp.), or their combination (77%, 75%, and 77%, resp.). Conclusions. Quantitative lung ultrasonography was considerably more accurate than either chest X-ray or visual ultrasonography in the diagnosis of community-acquired pneumonia and it may represent a useful first-line approach for confirmation of clinical diagnosis in emergency settings. Francesco Corradi, Claudia Brusasco, Alessandro Garlaschi, Francesco Paparo, Lorenzo Ball, Gregorio Santori, Paolo Pelosi, Fiorella Altomonte, Antonella Vezzani, and Vito Brusasco Copyright © 2015 Francesco Corradi et al. All rights reserved. Aqueous Cytokines as Predictors of Macular Edema in Patients with Diabetes following Uncomplicated Phacoemulsification Cataract Surgery Wed, 25 Feb 2015 07:57:07 +0000 This study aims to ascertain whether cytokines in the aqueous humor can predict macular edema (ME) in diabetic patients following uncomplicated phacoemulsification cataract surgery. Undiluted aqueous humor samples were obtained from 136 consecutive type 2 diabetic patients who underwent cataract surgery. The concentrations of 27 cytokines were measured in aqueous humor using the multiplex bead immunoassay. At the final follow-up examination, 116 patients completed 4 weeks of follow-up, and the incidence of macular edema was 29.31% (34 patients) 4 weeks after cataract surgery. Compared to the ME (−) patients, the concentrations of interleukin-1β (IL-1β) (), IL-6 (), IL-8 (), interferon-induced protein-10 (IP-10) (), monocyte chemotactic protein-1 (MCP-1) (), and vascular endothelial growth factor (VEGF) () in the ME (+) patients were significantly higher. In addition, the aqueous levels of IL-1β (), IL-6 (), IL-8 (), IP-10 (), MCP-1 (), and VEGF () were positively correlated with the postoperative foveal center point thickness (FCPT). However, the aqueous levels of IL-10 () and IL-12 () were significantly lower in patients with ME. These results suggest IL-1β, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, and VEGF may be potential predictors of postoperative macular thickness in patients with diabetes following uncomplicated phacoemulsification cataract surgery. Ning Dong, Bing Xu, Bingsong Wang, Liqun Chu, and Xin Tang Copyright © 2015 Ning Dong et al. All rights reserved. The Influence of Electromagnetic Pollution on Living Organisms: Historical Trends and Forecasting Changes Wed, 25 Feb 2015 06:42:13 +0000 Current technologies have become a source of omnipresent electromagnetic pollution from generated electromagnetic fields and resulting electromagnetic radiation. In many cases this pollution is much stronger than any natural sources of electromagnetic fields or radiation. The harm caused by this pollution is still open to question since there is no clear and definitive evidence of its negative influence on humans. This is despite the fact that extremely low frequency electromagnetic fields were classified as potentially carcinogenic. For these reasons, in recent decades a significant growth can be observed in scientific research in order to understand the influence of electromagnetic radiation on living organisms. However, for this type of research the appropriate selection of relevant model organisms is of great importance. It should be noted here that the great majority of scientific research papers published in this field concerned various tests performed on mammals, practically neglecting lower organisms. In that context the objective of this paper is to systematise our knowledge in this area, in which the influence of electromagnetic radiation on lower organisms was investigated, including bacteria, E. coli and B. subtilis, nematode, Caenorhabditis elegans, land snail, Helix pomatia, common fruit fly, Drosophila melanogaster, and clawed frog, Xenopus laevis. Grzegorz Redlarski, Bogdan Lewczuk, Arkadiusz Żak, Andrzej Koncicki, Marek Krawczuk, Janusz Piechocki, Kazimierz Jakubiuk, Piotr Tojza, Jacek Jaworski, Dominik Ambroziak, Łukasz Skarbek, and Dawid Gradolewski Copyright © 2015 Grzegorz Redlarski et al. All rights reserved. Development of Monoclonal Antibodies in China: Overview and Prospects Wed, 25 Feb 2015 06:23:51 +0000 Monoclonal antibodies (mAbs) have become increasingly important as human therapeutic agents. Yet, current research concentrates on technology itself and pays attention to developed countries. This paper aims to provide a comprehensive review of mAbs development in China through systematic analysis of drug registry, patent applications, clinical trials, academic publication, and ongoing R&D projects. The trends in therapeutic areas and industrialization process are also highlighted. Development and research trends of mAbs are analyzed to provide a future perspective of mAbs as therapeutic agents in China. Mao-Yu Zhang, Jin-Jian Lu, Liang Wang, Zi-Chao Gao, Hao Hu, Carolina Oi Lam Ung, and Yi-Tao Wang Copyright © 2015 Mao-Yu Zhang et al. All rights reserved.