BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Origanum dictamnus Oil Vapour Suppresses the Development of Grey Mould in Eggplant Fruit In Vitro Mon, 01 Sep 2014 13:17:10 +0000 Grey mould rot (Botrytis cinerea) development in vitro or in eggplant (Solanum melongena L.) fruit was evaluated after treatment with dittany (Origanum dictamnus L.) oil (DIT) and storage at 12°C and 95% relative humidity during or following exposure to the volatiles. DIT volatiles used in different concentration (0-50-100-250 μL/L) and times of exposure (up to 120 h) examined the effects on pathogen development as well as fruit quality parameters. In vitro, fungal colony growth was inhibited with the application of DIT oil (during or after exposure) and/or time of application. Continuous exposure to oils reduced conidial germination and production with fungistatic effects observed in 250 μL/L. In vivo, fungal lesion growth and conidial production reduced in DIT-treated fruits. Interesting, in fruits preexposed to volatiles before fungal inoculation, DIT application induced fruit resistance against the pathogen, by reduced lesion growth and conidial production. Conidial viability reduced in >100 μL/L DIT oil. Fruits exposed to essential oil did not affect fruit quality related attributes in general, while skin lightness (L value) increased in 50 and 100 μL/L DIT oil. The results of the current study indicated that dittany volatiles may be considered as an alternative food preservative, eliminating disease spread in the storage/transit atmospheres. Andriana Stavropoulou, Kostas Loulakakis, Naresh Magan, and Nikos Tzortzakis Copyright © 2014 Andriana Stavropoulou et al. All rights reserved. Vasopressin in Hemorrhagic Shock: A Systematic Review and Meta-Analysis of Randomized Animal Trials Mon, 01 Sep 2014 12:46:52 +0000 Objective. The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine) in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP), or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock. Design. A meta-analysis of randomized controlled animal trials. Participants. A total of 433 animals from 15 studies were included. Interventions. The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine), or placebo was investigated. Measurements and Main Results. Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15%) in the AVP group versus 164/259 (63%) in the control arms; ; 95% CI 0.05 to 0.15; for effect < 0.001; for heterogeneity = 0.30; ). Conclusions. Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials. Andrea Pasquale Cossu, Paolo Mura, Lorenzo Matteo De Giudici, Daniela Puddu, Laura Pasin, Maurizio Evangelista, Theodoros Xanthos, Mario Musu, and Gabriele Finco Copyright © 2014 Andrea Pasquale Cossu et al. All rights reserved. Giant Cell Arteritis: A Systematic Review of the Qualitative and Semiquantitative Methods to Assess Vasculitis with 18F-Fluorodeoxyglucose Positron Emission Tomography Mon, 01 Sep 2014 12:16:34 +0000 Giant cell arteritis (GCA) is the most common vasculitis affecting medium and large vessels. It shows a close clinical association with polymyalgia rheumatica (PMR), a musculoskeletal inflammatory disorder, which is clinically characterized by girdles pain and stiffness. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is an effective tool for the diagnosis, grading, and follow-up of patients affected by GCA involving the aorta and its proximal branches, but the lack of a standardized method for the assessment of vascular inflammation remains a critical issue, potentially leading to misclassification. In our systematic review, including 19 original articles for a total of 442 GCA patients (with or without PMR symptoms) and 535 healthy controls, we described the different qualitative, semiquantitative and combined methods that have been proposed throughout the literature for assessing the presence and grading the severity of GCA-related vascular inflammation on 18F-FDG PET scans, focusing on the diagnostic performance and examining their respective advantages and limitations. The majority of the included studies adopted qualitative methods of PET image analysis, which are less sensitive but more specific than semiquantitative ones. Among the semiquantitative approaches, the aortic-to-blood pool uptake ratio of the aortic arch seems to be the most accurate method. Cristina Puppo, Michela Massollo, Francesco Paparo, Dario Camellino, Arnoldo Piccardo, Mehrdad Shoushtari Zadeh Naseri, Giampiero Villavecchia, Gian Andrea Rollandi, and Marco Amedeo Cimmino Copyright © 2014 Cristina Puppo et al. All rights reserved. Efficacy of Intrauterine Device in the Treatment of Intrauterine Adhesions Mon, 01 Sep 2014 11:20:34 +0000 The primary purpose of this paper is to assess the efficacy of the use of the intrauterine device (IUD) as an adjunctive treatment modality, for intrauterine adhesions (IUAs). All eligible literatures were identified by electronic databases including PubMed, Scopus, and Web of Science. Additional relevant articles were identified from citations in these publications. There were 28 studies included for a systematic review. Of these, 5 studies were eligible for meta-analysis and 23 for qualitative assessment only. Twenty-eight studies related to the use of IUDs as ancillary treatment following adhesiolysis were identified. Of these studies, 25 studies at least one of the following methods were carried out as ancillary treatment: Foley catheter, hyaluronic acid gel, hormonal therapy, or amnion graft in addition to the IUD. There was one study that used IUD therapy as a single ancillary treatment. In 2 studies, no adjunctive therapy was used after adhesiolysis. There was a wide range of reported menstrual and fertility outcomes which were associated with the use of IUD combined with other ancillary treatments. At present, the IUD is beneficial in patients with IUA, regardless of stage of adhesions. However, IUD needs to be combined with other ancillary treatments to obtain maximal outcomes, in particular in patients with moderate to severe IUA. Umme Salma, Min Xue, Ali Sheikh Md Sayed, and Dabao Xu Copyright © 2014 Umme Salma et al. All rights reserved. Impact of the Prolymphangiogenic Crosstalk in the Tumor Microenvironment on Lymphatic Cancer Metastasis Mon, 01 Sep 2014 10:38:37 +0000 Lymphangiogenesis is a very early step in lymphatic metastasis. It is regulated and promoted not only by the tumor cells themselves, but also by cells of the tumor microenvironment, including cancer associated fibroblasts, mesenchymal stem cells, dendritic cells, or macrophages. Even the extracellular matrix as well as cytokines and growth factors are involved in the process of lymphangiogenesis and metastasis. The cellular and noncellular components influence each other and can be influenced by the tumor cells. The knowledge about mechanisms behind lymphangiogenesis in the tumor microenvironmental crosstalk is growing and offers starting points for new therapeutic approaches. Simona L. Schlereth, Nasrin Refaian, Sandra Iden, Claus Cursiefen, and Ludwig M. Heindl Copyright © 2014 Simona L. Schlereth et al. All rights reserved. Vitreous Substitutes: From Tamponade Effect to Intraocular Inflammation Mon, 01 Sep 2014 09:57:14 +0000 Mario R. Romano, Xun Xu, and Kenneth K. W. Li Copyright © 2014 Mario R. Romano et al. All rights reserved. Erratum to “Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet” Mon, 01 Sep 2014 09:18:00 +0000 Silvana Lorena Della Penna, Gabriel Cao, Andrea Carranza, Elsa Zotta, Susana Gorzalczany, Carolina Susana Cerrudo, Natalia Lucía Rukavina Mikusic, Alicia Correa, Verónica Trida, Jorge Eduardo Toblli, María Inés Rosón, and Belisario Enrique Fernández Copyright © 2014 Silvana Lorena Della Penna et al. All rights reserved. MicroRNA Profiling Reveals Unique miRNA Signatures in IGF-1 Treated Embryonic Striatal Stem Cell Fate Decisions in Striatal Neurogenesis In Vitro Mon, 01 Sep 2014 08:22:06 +0000 The striatum is considered to be the central processing unit of the basal ganglia in locomotor activity and cognitive function of the brain. IGF-1 could act as a control switch for the long-term proliferation and survival of EGF + bFGF-responsive cultured embryonic striatal stem cell (ESSC), while LIF imposes a negative impact on cell proliferation. The IGF-1-treated ESSCs also showed elevated hTERT expression with demonstration of self-renewal and trilineage commitment (astrocytes, oligodendrocytes, and neurons). In order to decipher the underlying regulatory microRNA (miRNA)s in IGF-1/LIF-treated ESSC-derived neurogenesis, we performed in-depth miRNA profiling at 12 days in vitro and analyzed the candidates using the Partek Genome Suite software. The annotated miRNA fingerprints delineated the differential expressions of miR-143, miR-433, and miR-503 specific to IGF-1 treatment. Similarly, the LIF-treated ESSCs demonstrated specific expression of miR-326, miR-181, and miR-22, as they were nonsignificant in IGF-treated ESSCs. To elucidate the possible downstream pathways, we performed in silico mapping of the said miRNAs into ingenuity pathway analysis. Our findings revealed the important mRNA targets of the miRNAs and suggested specific interactomes. The above studies introduced a new genre of miRNAs for ESSC-based neuroregenerative therapeutic applications. Soumya Pati, Nor Entan Supeno, Sangu Muthuraju, Raisah Abdul Hadi, Abdul Rahman Izaini Ghani, Fauziah Mohamad Idris, Mirjana Maletic-Savatic, Jafri Malin Abdullah, and Hasnan Jaafar Copyright © 2014 Soumya Pati et al. All rights reserved. Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma Mon, 01 Sep 2014 08:04:17 +0000 Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h ( %ID/g), compared with A375 tumor and inflammation lesion ( and  %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached  %ID/g at 2 h (versus  %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions. Shih-Yen Wu, Shih-Pin Huang, Yen-Chen Lo, Ren-Shyan Liu, Shyh-Jen Wang, Wuu-Jyh Lin, Chih-Chieh Shen, and Hsin-Ell Wang Copyright © 2014 Shih-Yen Wu et al. All rights reserved. Thai Massage, and Thai Herbal Compress versus Oral Ibuprofen in Symptomatic Treatment of Osteoarthritis of the Knee: A Randomized Controlled Trial Mon, 01 Sep 2014 05:56:54 +0000 The aim of this study was to verify the clinical responses to Thai massage (TM) and Thai herbal compression (THC) for treating osteoarthritis (OA) of the knee in comparison to oral ibuprofen. This study was a randomized, evaluator-blind, controlled trial. Sixty patients with OA of the knee were randomly assigned to receive either a one-hour session of TM or THC (three times weekly) or oral ibuprofen (three times daily). The duration of treatment was three weeks. The clinical assessments included visual analog scale assessing pain and stiffness, Lequesne’s functional index, time for climbing up ten steps, and physician’s and patient’s overall opinions on improvement. In a within-group comparison, each treatment modality caused a significant improvement of all variables determined for outcome assessments. In an among group comparison, all modalities provided nearly comparable clinical efficacy after a three-week symptomatic treatment of OA of the knee, in which a trend toward greatest improvement was likely to be found in THC group. In conclusion, TM and THC generally provided comparable clinical efficacy to oral ibuprofen after three weeks of treatment and could be considered as complementary and alternative treatments for OA of the knee. Natthakarn Chiranthanut, Nutthiya Hanprasertpong, and Supanimit Teekachunhatean Copyright © 2014 Natthakarn Chiranthanut et al. All rights reserved. Regulation of MicroRNAs by Natural Agents: New Strategies in Cancer Therapies Mon, 01 Sep 2014 05:44:54 +0000 MicroRNAs (miRNAs) are short noncoding RNA which regulate gene expression by messenger RNA (mRNA) degradation or translation repression. The plethora of published reports in recent years demonstrated that they play fundamental roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation by acting as tumour suppressor or oncogene, and aberrations in their expressions have been linked to onset and progression of various cancers. Furthermore, each miRNA is capable of regulating the expression of many genes, allowing them to simultaneously regulate multiple cellular signalling pathways. Hence, miRNAs have the potential to be used as biomarkers for cancer diagnosis and prognosis as well as therapeutic targets. Recent studies have shown that natural agents such as curcumin, resveratrol, genistein, epigallocatechin-3-gallate, indole-3-carbinol, and 3,3′-diindolylmethane exert their antiproliferative and/or proapoptotic effects through the regulation of one or more miRNAs. Therefore, this review will look at the regulation of miRNAs by natural agents as a means to potentially enhance the efficacy of conventional chemotherapy through combinatorial therapies. It is hoped that this would provide new strategies in cancer therapies to improve overall response and survival outcome in cancer patients. Neoh Hun Phuah and Noor Hasima Nagoor Copyright © 2014 Neoh Hun Phuah and Noor Hasima Nagoor. All rights reserved. Managing, Analysing, and Integrating Big Data in Medical Bioinformatics: Open Problems and Future Perspectives Mon, 01 Sep 2014 05:41:44 +0000 The explosion of the data both in the biomedical research and in the healthcare systems demands urgent solutions. In particular, the research in omics sciences is moving from a hypothesis-driven to a data-driven approach. Healthcare is additionally always asking for a tighter integration with biomedical data in order to promote personalized medicine and to provide better treatments. Efficient analysis and interpretation of Big Data opens new avenues to explore molecular biology, new questions to ask about physiological and pathological states, and new ways to answer these open issues. Such analyses lead to better understanding of diseases and development of better and personalized diagnostics and therapeutics. However, such progresses are directly related to the availability of new solutions to deal with this huge amount of information. New paradigms are needed to store and access data, for its annotation and integration and finally for inferring knowledge and making it available to researchers. Bioinformatics can be viewed as the “glue” for all these processes. A clear awareness of present high performance computing (HPC) solutions in bioinformatics, Big Data analysis paradigms for computational biology, and the issues that are still open in the biomedical and healthcare fields represent the starting point to win this challenge. Ivan Merelli, Horacio Pérez-Sánchez, Sandra Gesing, and Daniele D’Agostino Copyright © 2014 Ivan Merelli et al. All rights reserved. Bioassay Directed Isolation and Biological Evaluation of Compounds Isolated from Rubus fairholmianus Gard. Mon, 01 Sep 2014 05:09:15 +0000 The in vitro and in silico analysis of Rubus fairholmianus acetone extract for antioxidant, antiproliferative, and anti-inflammatory activity led to the isolation of six compounds. Amongst all the six isolated compounds tested, 1-(2-hydroxyphenyl)-4-methylpentan-1-one (compound 1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (compound 2) were found to be more active in inhibiting BRCA and COX target proteins, which also showed the better results for DPPH and ABTS radical scavenging assays. The promising results of this investigation emphasize the importance of using R. fairholmianus in the treatment of radical generated disorders mainly cancer and other inflammatory diseases. Blassan Plackal George, Parimelazhagan Thangaraj, Cheruthazhakkatt Sulaiman, Shanmughavel Piramanayagam, and Sathish Kumar Ramaswamy Copyright © 2014 Blassan Plackal George et al. All rights reserved. The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma Sun, 31 Aug 2014 11:54:15 +0000 Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC’s survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma. Haitao Wang, Rikang Wang, Thilini Thrimawithana, Peter J. Little, Jiangping Xu, Zhong-Ping Feng, and Wenhua Zheng Copyright © 2014 Haitao Wang et al. All rights reserved. Association of vWA and TPOX Polymorphisms with Venous Thrombosis in Mexican Mestizos Sun, 31 Aug 2014 11:10:24 +0000 Objective. Venous thromboembolism (VTE) is a multifactorial disorder and, worldwide, the most important cause of morbidity and mortality. Genetic factors play a critical role in its aetiology. Microsatellites are the most important source of human genetic variation having more phenotypic effect than many single nucleotide polymorphisms. Hence, we evaluate a possible relationship between VTE and the genetic variants in von Willebrand factor, human alpha fibrinogen, and human thyroid peroxidase microsatellites to identify possible diagnostic markers. Methods. Genotypes were obtained from 177 patients with VTE and 531 nonrelated individuals using validated genotyping methods. The allelic frequencies were compared; Bayesian methods were used to correct population stratification to avoid spurious associations. Results. The vWA-18, TPOX-9, and TPOX-12 alleles were significantly associated with VTE. Moreover, subjects bearing the combination vWA-18/TPOX-12 loci exhibited doubled risk for VTE (95% CI = 1.02–3.64), whereas the combination vWA-18/TPOX-9 showed an OR = 10 (95% CI = 4.93–21.49). Conclusions. The vWA and TPOX microsatellites are good candidate biomarkers in venous thromboembolism diseases and could help to elucidate their origins. Additionally, these polymorphisms could become useful markers for genetic studies of VTE in the Mexican population; however, further studies should be done owing that this data only show preliminary evidence. Marco Antonio Meraz-Ríos, Abraham Majluf-Cruz, Carla Santana, Gino Noris, Rafael Camacho-Mejorado, Leonor C. Acosta-Saavedra, Emma S. Calderón-Aranda, Jesús Hernández-Juárez, Jonathan J. Magaña, and Rocío Gómez Copyright © 2014 Marco Antonio Meraz-Ríos et al. All rights reserved. Are Applied Growth Factors Able to Mimic the Positive Effects of Mesenchymal Stem Cells on the Regeneration of Meniscus in the Avascular Zone? Sun, 31 Aug 2014 10:49:11 +0000 Meniscal lesions in the avascular zone are still a problem in traumatology. Tissue Engineering approaches with mesenchymal stem cells (MSCs) showed successful regeneration of meniscal defects in the avascular zone. However, in daily clinical practice, a single stage regenerative treatment would be preferable for meniscus injuries. In particular, clinically applicable bioactive substances or isolated growth factors like platelet-rich plasma (PRP) or bone morphogenic protein 7 (BMP7) are in the focus of interest. In this study, the effects of PRP and BMP7 on the regeneration of avascular meniscal defects were evaluated. In vitro analysis showed that PRP secretes multiple growth factors over a period of 8 days. BMP7 enhances the collagen II deposition in an aggregate culture model of MSCs. However applied to meniscal defects PRP or BMP7 in combination with a hyaluronan collagen composite matrix failed to significantly improve meniscus healing in the avascular zone in a rabbit model after 3 months. Further information of the repair mechanism at the defect site is needed to develop special release systems or carriers for the appropriate application of growth factors to support biological augmentation of meniscus regeneration. Johannes Zellner, Christian Dirk Taeger, Markus Schaffer, J. Camilo Roldan, Markus Loibl, Michael B. Mueller, Arne Berner, Werner Krutsch, Michaela K. I. Huber, Richard Kujat, Michael Nerlich, and Peter Angele Copyright © 2014 Johannes Zellner et al. All rights reserved. L-Methionase: A Therapeutic Enzyme to Treat Malignancies Sun, 31 Aug 2014 10:04:30 +0000 Cancer is an increasing cause of mortality and morbidity throughout the world. L-methionase has potential application against many types of cancers. L-Methionase is an intracellular enzyme in bacterial species, an extracellular enzyme in fungi, and absent in mammals. L-Methionase producing bacterial strain(s) can be isolated by 5,5′-dithio-bis-(2-nitrobenzoic acid) as a screening dye. L-Methionine plays an important role in tumour cells. These cells become methionine dependent and eventually follow apoptosis due to methionine limitation in cancer cells. L-Methionine also plays an indispensable role in gene activation and inactivation due to hypermethylation and/or hypomethylation. Membrane transporters such as GLUT1 and ion channels like Na2+, Ca2+, K+, and Cl− become overexpressed. Further, the α-subunit of ATP synthase plays a role in cancer cells growth and development by providing them enhanced nutritional requirements. Currently, selenomethionine is also used as a prodrug in cancer therapy along with enzyme methionase that converts prodrug into active toxic chemical(s) that causes death of cancerous cells/tissue. More recently, fusion protein (FP) consisting of L-methionase linked to annexin-V has been used in cancer therapy. The fusion proteins have advantage that they have specificity only for cancer cells and do not harm the normal cells. Bhupender Sharma, Sukhdev Singh, and Shamsher S. Kanwar Copyright © 2014 Bhupender Sharma et al. All rights reserved. Accuracy of Patient Specific Cutting Blocks in Total Knee Arthroplasty Sun, 31 Aug 2014 09:03:06 +0000 Background. Long-term survival of total knee arthroplasty (TKA) is mainly determined by optimal positioning of the components and prosthesis alignment. Implant positioning can be optimized by computer assisted surgery (CAS). Patient specific cutting blocks (PSCB) seem to have the potential to improve component alignment compared to the conventional technique and to be comparable to CAS. Methods. 113 knees were selected for PSI and included in this study. Pre- and postoperative mechanical axis, represented by the hip-knee-angle (HKA), the proximal tibial angle (PTA), the distal femoral angle (DFA), and the tibial slope (TS) were measured and the deviation from expected ideal values was calculated. Results. With a margin of error of ±3°, success rates were 81.4% for HKA, 92.0% for TPA, and 94.7% for DFA. With the margin of error for alignments extended to ±4°, we obtained a success rate of 92.9% for the HKA, 98.2% for the PTA, and 99.1% for the DFA. The TS showed postoperative results of 2.86 ± 2.02° (mean change 1.76 ± 2.85°). Conclusion. PSCBs for TKA seem to restore the overall leg alignment. Our data suggest that each individual component can be implanted accurately and the results are comparable to the ones in CAS. Naeder Helmy, Mai Lan Dao Trong, and Stefanie P. Kühnel Copyright © 2014 Naeder Helmy et al. All rights reserved. A Derived Network-Based Interferon-Related Signature of Human Macrophages Responding to Mycobacterium tuberculosis Sun, 31 Aug 2014 08:10:43 +0000 Network analysis of transcriptional signature typically relies on direct interaction between two highly expressed genes. However, this approach misses indirect and biological relevant interactions through a third factor (hub). Here we determine whether a hub-based network analysis can select an improved signature subset that correlates with a biological change in a stronger manner than the original signature. We have previously reported an interferon-related transcriptional signature (THP1r2Mtb-induced) from Mycobacterium tuberculosis (M. tb)-infected THP-1 human macrophage. We selected hub-connected THP1r2Mtb-induced genes into the refined network signature TMtb-iNet and grouped the excluded genes into the excluded signature TMtb-iEx. TMtb-iNet retained the enrichment of binding sites of interferon-related transcription factors and contained relatively more interferon-related interacting genes when compared to THP1r2Mtb-induced signature. TMtb-iNet correlated as strongly as THP1r2Mtb-induced signature on a public transcriptional dataset of patients with pulmonary tuberculosis (PTB). TMtb-iNet correlated more strongly in CD4+ and CD8+ T cells from PTB patients than THP1r2Mtb-induced signature and TMtb-iEx. When TMtb-iNet was applied to data during clinical therapy of tuberculosis, it resulted in the most pronounced response and the weakest correlation. Correlation on dataset from patients with AIDS or malaria was stronger for TMtb-iNet, indicating an involvement of TMtb-iNet in these chronic human infections. Collectively, the significance of this work is twofold: (1) we disseminate a hub-based approach in generating a biologically meaningful and clinically useful signature; (2) using this approach we introduce a new network-based signature and demonstrate its promising applications in understanding host responses to infections. Kang Wu, Hai Fang, Liang-Dong Lyu, Douglas B. Lowrie, Ka-Wing Wong, and Xiao-Yong Fan Copyright © 2014 Kang Wu et al. All rights reserved. Hypolipidemic and Antioxidant Activity of Enoki Mushrooms (Flammulina velutipes) Sun, 31 Aug 2014 08:08:04 +0000 According to the literatures, Flammulina velutipes contains biologically active components such as dietary fiber, polysaccharide, and mycosterol, whose effects in reducing blood sugar, blood pressure, and cholesterol have been proven. This study used the active components extracted from Flammulina velutipes powder (FVP) and Flammulina velutipes extract (FVE) to investigate the impact of these active components on lipid metabolism of hamsters. The results show that the total dietary fiber content in FVP and FVE is 29.34 mg/100 g and 15.08 mg/100 g, respectively. The total mycosterol content is 46.57 ± 0.37 mg/100 g and 9.01 ± 0.17 mg/100 g, respectively. The male hamsters were subjected to lipid metabolism monitoring by adding 1, 2, and 3% FVP or FVE into their diets for a period of 8 weeks. The animal assay results show that the 3% FVP and FVE groups have the lowest concentration of TC (total cholesterol), TG (triacylglycerol), LDL (low density lipoprotein cholesterol), and LDL/HDL (high density lipoprotein cholesterol) in the serum and liver (P < 0.05). Our results demonstrate that the addition of 3% FVP or FVE has a significant effect on the lipid metabolism in hamsters whose increased level of HDL in the serum was induced by high fat diet. Ming-Yei Yeh, Wen-Ching Ko, and Li-Yun Lin Copyright © 2014 Ming-Yei Yeh et al. All rights reserved. Role of Feed Forward Neural Networks Coupled with Genetic Algorithm in Capitalizing of Intracellular Alpha-Galactosidase Production by Acinetobacter sp. Sun, 31 Aug 2014 08:07:46 +0000 Alpha-galactosidase production in submerged fermentation by Acinetobacter sp. was optimized using feed forward neural networks and genetic algorithm (FFNN-GA). Six different parameters, pH, temperature, agitation speed, carbon source (raffinose), nitrogen source (tryptone), and K2HPO4, were chosen and used to construct 6-10-1 topology of feed forward neural network to study interactions between fermentation parameters and enzyme yield. The predicted values were further optimized by genetic algorithm (GA). The predictability of neural networks was further analysed by using mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and R2-value for training and testing data. Using hybrid neural networks and genetic algorithm, alpha-galactosidase production was improved from 7.5 U/mL to 10.2 U/mL. Sirisha Edupuganti, Ravichandra Potumarthi, Thadikamala Sathish, and Lakshmi Narasu Mangamoori Copyright © 2014 Sirisha Edupuganti et al. All rights reserved. Effects of Microbubble Size on Ultrasound-Mediated Gene Transfection in Auditory Cells Sun, 31 Aug 2014 08:06:16 +0000 Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cells in vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced. Ai-Ho Liao, Yi-Lei Hsieh, Hsin-Chiao Ho, Hang-Kang Chen, Yi-Chun Lin, Cheng-Ping Shih, Hsin-Chien Chen, Chao-Yin Kuo, Ying-Jui Lu, and Chih-Hung Wang Copyright © 2014 Ai-Ho Liao et al. All rights reserved. Proteomics Analysis for Finding Serum Markers of Ovarian Cancer Sun, 31 Aug 2014 07:50:14 +0000 A combination of peptide ligand library beads (PLLB) and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS) was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4) is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value  ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals ( ng/mL). Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer. Yushan Cheng, Chongdong Liu, Nawei Zhang, Shengdian Wang, and Zhenyu Zhang Copyright © 2014 Yushan Cheng et al. All rights reserved. Marked Antigiardial Activity of Yucca baccata Extracts: A Potential Natural Alternative for Treating Protozoan Infections Sun, 31 Aug 2014 07:19:48 +0000 Human Giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis. Luis Quihui-Cota, Rocio León-Trujillo, Humberto Astiazarán-García, Julián Esparza-Romero, María del Refugio Robles, Ramón E. Robles-Zepeda, Rafael Canett, and Jesús Sánchez-Escalante Copyright © 2014 Luis Quihui-Cota et al. All rights reserved. Autophagy: A Multifaceted Partner in Liver Fibrosis Sun, 31 Aug 2014 07:10:23 +0000 Liver fibrosis is a common wound healing response to chronic liver injury of all causes, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Fibrosis results from prolonged parenchymal cell apoptosis and necrosis associated with an inflammatory reaction that leads to recruitment of immune cells, activation and accumulation of fibrogenic cells, and extracellular matrix accumulation. The fibrogenic process is driven by hepatic myofibroblasts, that mainly derive from hepatic stellate cells undergoing a transdifferentiation from a quiescent, lipid-rich into a fibrogenic myofibroblastic phenotype, in response to paracrine/autocrine signals produced by neighbouring inflammatory and parenchymal cells. Autophagy is an important regulator of liver homeostasis under physiological and pathological conditions. This review focuses on recent findings showing that autophagy is a novel, but complex, regulatory pathway in liver fibrosis, with profibrogenic effects relying on its direct contribution to the process of hepatic stellate cell activation, but with antifibrogenic properties via indirect hepatoprotective and anti-inflammatory properties. Therefore, cell-specific delivery of drugs that exploit autophagic pathways is a prerequisite to further consider autophagy as a potential target for antifibrotic therapy. Ariane Mallat, Jasper Lodder, Fatima Teixeira-Clerc, Richard Moreau, Patrice Codogno, and Sophie Lotersztajn Copyright © 2014 Ariane Mallat et al. All rights reserved. A Review of Feature Extraction Software for Microarray Gene Expression Data Sun, 31 Aug 2014 07:10:08 +0000 When gene expression data are too large to be processed, they are transformed into a reduced representation set of genes. Transforming large-scale gene expression data into a set of genes is called feature extraction. If the genes extracted are carefully chosen, this gene set can extract the relevant information from the large-scale gene expression data, allowing further analysis by using this reduced representation instead of the full size data. In this paper, we review numerous software applications that can be used for feature extraction. The software reviewed is mainly for Principal Component Analysis (PCA), Independent Component Analysis (ICA), Partial Least Squares (PLS), and Local Linear Embedding (LLE). A summary and sources of the software are provided in the last section for each feature extraction method. Ching Siang Tan, Wai Soon Ting, Mohd Saberi Mohamad, Weng Howe Chan, Safaai Deris, and Zuraini Ali Shah Copyright © 2014 Ching Siang Tan et al. All rights reserved. Abnormal Functional Resting-State Networks in ADHD: Graph Theory and Pattern Recognition Analysis of fMRI Data Sun, 31 Aug 2014 00:00:00 +0000 The framework of graph theory provides useful tools for investigating the neural substrates of neuropsychiatric disorders. Graph description measures may be useful as predictor variables in classification procedures. Here, we consider several centrality measures as predictor features in a classification algorithm to identify nodes of resting-state networks containing predictive information that can discriminate between typical developing children and patients with attention-deficit/hyperactivity disorder (ADHD). The prediction was based on a support vector machines classifier. The analyses were performed in a multisite and publicly available resting-state fMRI dataset of healthy children and ADHD patients: the ADHD-200 database. Network centrality measures contained little predictive information for the discrimination between ADHD patients and healthy subjects. However, the classification between inattentive and combined ADHD subtypes was more promising, achieving accuracies higher than 65% (balance between sensitivity and specificity) in some sites. Finally, brain regions were ranked according to the amount of discriminant information and the most relevant were mapped. As hypothesized, we found that brain regions in motor, frontoparietal, and default mode networks contained the most predictive information. We concluded that the functional connectivity estimations are strongly dependent on the sample characteristics. Thus different acquisition protocols and clinical heterogeneity decrease the predictive values of the graph descriptors. Anderson dos Santos Siqueira, Claudinei Eduardo Biazoli Junior, William Edgar Comfort, Luis Augusto Rohde, and João Ricardo Sato Copyright © 2014 Anderson dos Santos Siqueira et al. All rights reserved. Destabilization of Akt Promotes the Death of Myeloma Cell Lines Sun, 31 Aug 2014 00:00:00 +0000 Constitutive activation of Akt is believed to be an oncogenic signal in multiple myeloma and is associated with poor patient prognosis and resistance to available treatment. The stability of Akt proteins is regulated by phosphorylating the highly conserved turn motif (TM) of these proteins and the chaperone protein HSP90. In this study we investigate the antitumor effects of inhibiting mTORC2 plus HSP90 in myeloma cell lines. We show that chronic exposure of cells to rapamycin can inhibit mTORC2 pathway, and AKT will be destabilized by administration of the HSP90 inhibitor 17-allylamino-geldanamycin (17-AAG). Finally, we show that the rapamycin synergizes with 17-AAG and inhibits myeloma cells growth and promotes cell death to a greater extent than either drug alone. Our studies provide a clinical rationale of use mTOR inhibitors and chaperone protein inhibitors in combination regimens for the treatment of human blood cancers. Yanan Zhang, Yunfeng Fu, Fan Zhang, and Jing Liu Copyright © 2014 Yanan Zhang et al. All rights reserved. Evaluation of Corneal Biomechanical Properties Modification after Small Incision Lenticule Extraction Using Scheimpflug-Based Noncontact Tonometer Sun, 31 Aug 2014 00:00:00 +0000 Purpose. To quantify the effect of small incision lenticule extraction (SMILE) on the corneal biomechanics using Scheimpflug noncontact tonometer (Corvis ST). Methods. Twenty eyes of twenty patients, evaluated as eligible for surgery, with high myopia and/or moderate myopic astigmatism, underwent small incision lenticule extraction (SMILE). All patients underwent Corvis ST preoperatively and postoperatively after 1 week, and 1 and 3 months to observe alterations of corneal biomechanical properties. The main outcome measures were Deformation Amplitude, 1st-AT, and 2nd-AT. The relationship between the amount of stroma removed and the percentage variation of the measured parameters from baseline was evaluated with generalized linear model from each time point. For completeness also intraocular pressure (IOP), central corneal thickness (CCT), and their variations after surgery were evaluated. Results. The ratio between the amount of removed refractive error and, respectively, changes of Deformation Amplitude, 1st-AT, and 2nd-AT were significantly modified at the 1st week after surgery . At 1 and 3 months these values did not show statistically significant alterations. Intraocular pressure and central corneal thickness showed statistically significant changes during follow-up. Conclusions. No significant modifications in biomechanical properties were observed after SMILE so this procedure could induce only minimal transient alterations of corneal biomechanics. Leonardo Mastropasqua, Roberta Calienno, Manuela Lanzini, Martina Colasante, Alessandra Mastropasqua, Peter A. Mattei, and Mario Nubile Copyright © 2014 Leonardo Mastropasqua et al. All rights reserved. A New Method for Feedback on the Quality of Chest Compressions during Cardiopulmonary Resuscitation Thu, 28 Aug 2014 15:37:54 +0000 Quality of cardiopulmonary resuscitation (CPR) improves through the use of CPR feedback devices. Most feedback devices integrate the acceleration twice to estimate compression depth. However, they use additional sensors or processing techniques to compensate for large displacement drifts caused by integration. This study introduces an accelerometer-based method that avoids integration by using spectral techniques on short duration acceleration intervals. We used a manikin placed on a hard surface, a sternal triaxial accelerometer, and a photoelectric distance sensor (gold standard). Twenty volunteers provided 60 s of continuous compressions to test various rates (80–140 min−1), depths (3–5 cm), and accelerometer misalignment conditions. A total of 320 records with 35312 compressions were analysed. The global root-mean-square errors in rate and depth were below 1.5 min−1 and 2 mm for analysis intervals between 2 and 5 s. For 3 s analysis intervals the 95% levels of agreement between the method and the gold standard were within −1.64–1.67 min−1 and −1.69–1.72 mm, respectively. Accurate feedback on chest compression rate and depth is feasible applying spectral techniques to the acceleration. The method avoids additional techniques to compensate for the integration displacement drift, improving accuracy, and simplifying current accelerometer-based devices. Digna M. González-Otero, Jesus Ruiz, Sofía Ruiz de Gauna, Unai Irusta, Unai Ayala, and Erik Alonso Copyright © 2014 Digna M. González-Otero et al. All rights reserved.