bluuebunny/crossref_metadata_2025 huggingface dataset:
Antinociceptive and anti-inflammatory activities of Geranium bellum and its isolated compounds
Authors: Velázquez-González Claudia , Cariño-Cortés Raquel , Gayosso de Lucio Juan A , Ortiz Mario I , De la O Arciniega Minarda , Altamirano-Báez Diana A , Ángeles Luis Jiménez- , Bautista-Ávila Mirandeli
Published: June 2015

Background

Geranium bellum Rose, locally known as “Pata de león”, is a perennial plant distributed in the mountains of Hidalgo, Mexico. It is widely used in Mexican traditional medicine to treat fever, pain, and gastrointestinal disorders. To date, there are not published studies regarding the in vivo antinociceptive and anti-inflammatory potential of the acetone-aqueous extract from the aerial parts of G. bellum.

Methods

Antinociceptive effects of the acetone-aqueous G. bellum (AGB) extract and the isolated compounds were assessed using experimental pain models, including thermal nociception like hot plate test, and chemical nociception induced by intraperitoneal acetic acid or subplantar formalin injection in vivo. The anti-inflammatory properties of the extract were studied using systemic administration in carrageenan-induced paw edema.

Results

Intra-gastric administration of AGB (75, 150, and 300 mg/kg) showed a dose-dependent antinociceptive effect in intraperitoneal acetic acid (writhing), thermal nociception in CD1 mice, and subplantar formalin models, as well as anti-inflammatory effect in carrageenan- induced paw edema in Wistar rats. Geraniin and quercetin showed the highest antinociceptive activity in writhing test, whereas ellagic acid was the most active compound in the hot plate model.

Conclusion

These studies provide evidences that G. bellum shows antinociceptive and anti- inflammatory effects, and gives support to its use in treating pain in Mexican traditional medicine.
Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles
Authors: Dian Linghui , Yu Enjiang , Chen Xiaona , Wen Xinguo , Zhang Zhengzan , Qin Lingzhen , Wang Qingqing , Li Ge , Wu Chuanbin
Published: June 2015

To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.
Synthesis of gallium nitride nanostructures by nitridation of electrochemically deposited gallium oxide on silicon substrate
Authors: Ghazali Norizzawati Mohd , Yasui Kanji , Hashim Abdul Manaf
Published: June 2015

Gallium nitride (GaN) nanostructures were successfully synthesized by the nitridation of the electrochemically deposited gallium oxide (Ga2O3) through the utilization of a so-called ammoniating process. Ga2O3 nanostructures were firstly deposited on Si substrate by a simple two-terminal electrochemical technique at a constant current density of 0.15 A/cm2 using a mixture of Ga2O3, HCl, NH4OH and H2O for 2 h. Then, the deposited Ga2O3 sample was ammoniated in a horizontal quartz tube single zone furnace at various ammoniating times and temperatures. The complete nitridation of Ga2O3 nanostructures at temperatures of 850°C and below was not observed even the ammoniating time was kept up to 45 min. After the ammoniating process at temperature of 900°C for 15 min, several prominent diffraction peaks correspond to hexagonal GaN (h-GaN) planes were detected, while no diffraction peak of Ga2O3 structure was detected, suggesting a complete transformation of Ga2O3 to GaN. Thus, temperature seems to be a key parameter in a nitridation process where the deoxidization rate of Ga2O3 to generate gaseous Ga2O increase with temperature. The growth mechanism for the transformation of Ga2O3 to GaN was proposed and discussed. It was found that a complete transformation can not be realized without a complete deoxidization of Ga2O3. A significant change of morphological structures takes place after a complete transformation of Ga2O3 to GaN where the original nanorod structures of Ga2O3 diminish, and a new nanowire-like GaN structures appear. These results show that the presented method seems to be promising in producing high-quality h-GaN nanostructures on Si.
Half metal in two-dimensional hexagonal organometallic framework
Authors: Hu Hao , Wang Zhengfei , Liu Feng
Published: June 2015

Two-dimensional (2D) hexagonal organometallic framework (HOMF) made of triphenyl-metal molecules bridged by metal atoms has been recently shown to exhibit exotic electronic properties, such as half-metallic and topological insulating states. Here, using first-principles calculations, we investigate systematically the structural, electronic, and magnetic properties of such HOMFs containing 3d transition metal (TM) series (Sc to Cu). Two types of structures are found for these HOMFs: a buckled structure for those made of TMs with less half-filled 3d band and a twisted structure otherwise. The HOMFs show both ferromagnetic and antiferromagnetic properties, as well as nonmagnetic properties, due to the electronic configuration of the TM atoms. The V, Mn, and Fe lattices are ferromagnetic half metals with a large band gap of more than 1.5 eV in the insulating spin channel, making them potential 2D materials for spintronics application.
Enhanced performance of nitride-based ultraviolet vertical-injection light-emitting diodes by non-insulation current blocking layer and textured surface
Authors: Chiang Yen Chih , Lin Bing Cheng , Chen Kuo Ju , Lin Chien Chung , Lee Po Tsung , Kuo Hao Chung
Published: June 2015

For the purpose of light extraction and efficiency enhancement, the nitride-based ultraviolet vertical-injection light-emitting diodes (UV-VLEDs) with non-insulation current blocking layer (n-CBL) and optimized textured surface were fabricated. The optical and electrical characteristics were investigated in this n-CBL UV-VLED. Furthermore, the efficiency of optimized structure was improved by 5 ~ 6 times compared to our reference.
Improved spectrum sensing for OFDM cognitive radio in the presence of timing offset
Authors: Shi Zhenguo , McLernon Des , Ghogho Mounir , Wu Zhilu
Published: June 2015

Spectrum sensing is an important aspect of an (interweave) cognitive radio network. In the particular case of orthogonal frequency division multiplexing (OFDM) transmission, many previous spectrum sensing algorithms have utilized the unique correlation properties provided by the cyclic prefix (CP). However, they have also had to both estimate and compensate for the inherent timing offset of a practical system. This is because the timing offset will affect both the test statistic and the threshold, and the inaccurate estimation of timing offset will lead to poor performance. So in this paper, we propose an improved CP detector by constructing a likelihood ratio test (LRT) based on the multivariate probability density functions (pdf) of a particular auto-correlation vector that is chosen to exploit the existence of the CP. This leads to ‘probability of detection’ (P

d
) and ‘probability of false alarm’ (P

f
) terms that are actually independent of timing offset, and we can get an accurate threshold without estimating timing offset. Simulation results illustrate that the proposed algorithm outperforms existing methods, even for low SNR values. Finally, we show how the algorithm’s parameters must be carefully chosen in a trade-off between spectrum sensing success and overall system performance.
MIMO channel capacity using antenna selection and water pouring
Authors: Cuan-Cortes Jose V , Vargas-Rosales Cesar , Munoz-Rodriguez David
Published: June 2015

The use of multiple-input multiple-output (MIMO) communication systems has attracted considerable attention due to capacity and performance improvements without increasing the required bandwidth or transmission power. Although MIMO improves the transmission rate and provides reliable communication, these advantages come at a high cost, since multiple radio frequency (RF) chains have to be employed. Therefore, cost-effective implementation of MIMO systems remains as an important challenge. In this sense, antenna selection techniques (AST) can help reduce the high cost of MIMO systems, while retaining most of their benefits; and in order to improve channel capacity, transmission power can be allocated efficiently according to the channel experienced by each antenna element. In this paper, we show the channel capacity improvement of MIMO systems, by combining the use of AST and transmission power allocation through the water-pouring algorithm (WPA) for different antenna configurations. We apply WPA and allocate more power to the channel with better conditions, when the MIMO channel is Rayleigh distributed and noise is Gaussian. By employing these two techniques (AST and WPA), we show that channel capacity is significantly improved, with higher capacity values than those obtained using traditional systems which just spread equal power among all the transmit antennas. We also show that bounds on the capacity can be considered when these improvements are used in a MIMO system.
A simultaneous iterative method for split equality problems of two finitefamilies of strictly pseudononspreading mappings without prior knowledge ofoperator norms
Authors: Che Haitao , Li Meixia
Published: June 2015

In this article, we first introduce the concept of T-mapping of a finitefamily of strictly pseudononspreading mapping "Equation missing", and we show that the fixed point set of theT-mapping is the set of common fixed points of"Equation missing" and T is a quasi-nonexpansive mapping.Based on the concept of a T-mapping, we propose a simultaneousiterative algorithm to solve the split equality problem with a way of selectingthe stepsizes which does not need any prior information about the operatornorms. The sequences generated by the algorithm weakly converge to a solution ofthe split equality problem of two finite families of strictly pseudononspreadingmappings. Furthermore, we apply our iterative algorithms to some convex andnonlinear problems.

MSC: 47H09, 47H05, 47H06, 47J25.
Computer-assisted analysis of painting brushstrokes: digital image processing for unsupervised extraction of visible features from van Gogh’s works
Authors: Lamberti Fabrizio , Sanna Andrea , Paravati Gianluca
Published: June 2015

The automatic extraction of objective features from paintings, like brushstroke distribution, orientation, and shape, could be particularly useful for different artwork analyses and management tasks. In fact, these features contribute to provide a unique signature of the artists’ style and can be effectively used for artist identification and classification, artwork examination and retrieval, etc. In this paper, an automatic technique for unsupervised extraction of individual brushstrokes from digital reproductions of van Gogh’s paintings is presented. Through the iterative application of segmentation, characterization, and validation steps, valid brushstrokes complying with specific area and shape constraints are identified. On the extracted brushstrokes, several representative features can then be calculated, like orientation, length, and width. The accuracy of the devised method is evaluated by comparing numerical results obtained on a dataset of digital reproductions of van Gogh’s oil-on-canvas works with observations made by human subjects and with another recent approach for automatic brushstroke analysis. Experimental tests showed that the devised methodology produces results that are rather close to those obtained by human subjects and, for some of the metrics considered, can provide improved performances with respect to alternative techniques.
Genetic, Epigenetic, and Mechanistic Studies of Temporomandibular Disorders and Overlapping Pain Conditions
Authors: Munzenmaier Diane H , Wilentz Joan , Cowley Allen W
Published: June 2015

Leaders in the fields of Temporomandibular Disorders (TMD) and its accompanying overlapping pain conditions presented their latest findings at the Seventh Scientific Meeting of The TMJ Association, September 7–9, 2014, in Bethesda, MD. The meeting was co-sponsored by The TMJ Association and the National Institutes of Health. Topics of the scientific sessions included epidemiology and diagnostic criteria, basic mechanisms of chronic pain including the genetic and epigenetic basis of chronic pain, and the development of novel drugs for treatment of these conditions. Discussions were directed toward formulating a set of recommendations to advance research in this field.
Spinal Autophagy is Differently Modulated in Distinct Mouse Models of Neuropathic Pain
Authors: Berliocchi Laura , Maiarù Maria , Varano Giuseppe Pasquale , Russo Rossella , Corasaniti Maria Tiziana , Bagetta Giacinto , Tassorelli Cristina
Published: June 2015

Background

Autophagy is a homeostatic degradative process essential for basal turnover of long-lived proteins and organelles as well as for removal of dysfunctional cellular components. Dysregulation of the autophagic machinery has been recently associated to several conditions including neurodegenerative diseases and cancer, but only very few studies have investigated its role in pain processing.

Results

We previously described autophagy impairment at the spinal cord in the experimental model of neuropathic pain induced by spinal nerve ligation (SNL). In this study, we characterized the main autophagic markers in two other common experimental models of neuropathic pain, the chronic constriction injury (CCI) and the spared nerve injury (SNI). The different modulation of LC3-I, Beclin 1 and p62 suggested that autophagy is differentially affected in the spinal dorsal horn depending on the type of peripheral injury. Confocal analysis of p62 distribution in the spinal dorsal horn indicated its presence mainly in NeuN-positive cell bodies and occasionally in glial processes, thus suggesting a predominant expression in the neuronal compartment. Finally, we investigated the consequences of autophagy impairment on pain behaviour by using the autophagy blocker cloroquine. Intrathecal chloroquine injection in naïve mice induced spinal accumulation of LC3 and p62 paralleled by significant mechanical hypersensitivity thus confirming the block in autophagosome clearance and suggesting the participation of the autophagic process in spinal mechanisms of pain processing. Altogether, our data indicate that spinal autophagy is differentially altered in different experimental pain models of neuropathic pain and that this process may be relevant for pain control.
A CRF-based system for recognizing chemical entity mentions (CEMs) in biomedical literature
Authors: Xu Shuo , An Xin , Zhu Lijun , Zhang Yunliang , Zhang Haodong
Published: June 2015

Background

In order to improve information access on chemical compounds and drugs (chemical entities) described in text repositories, it is very crucial to be able to identify chemical entity mentions (CEMs) automatically within text. The CHEMDNER challenge in BioCreative IV was specially designed to promote the implementation of corresponding systems that are able to detect mentions of chemical compounds and drugs, which has two subtasks: CDI (Chemical Document Indexing) and CEM.

Results

Our system processing pipeline consists of three major components: pre-processing (sentence detection, tokenization), recognition (CRF-based approach), and post-processing (rule-based approach and format conversion). In our post-challenge system, the cost parameter in CRF model was optimized by 10-fold cross validation with grid search, and word representations feature induced by Brown clustering method was introduced. For the CEM subtask, our official runs were ranked in top position by obtaining maximum 88.79% precision, 69.08% recall and 77.70% balanced F-measure, which were improved further to 88.43% precision, 76.48% recall and 82.02% balanced F-measure in our post-challenge system.

Conclusions

In our system, instead of extracting a CEM as a whole, we regarded it as a sequence labeling problem. Though our current system has much room for improvement, our system is valuable in showing that the performance in term of balanced F-measure can be improved largely by utilizing large amounts of relatively inexpensive un-annotated PubMed abstracts and optimizing the cost parameter in CRF model. From our practice and lessons, if one directly utilizes some open-source natural language processing (NLP) toolkits, such as OpenNLP, Standford CoreNLP, false positive (FP) rate may be very high. It is better to develop some additional rules to minimize the FP rate if one does not want to re-train the related models. Our CEM recognition system is available at: http://www.SciTeMiner.org/XuShuo/Demo/CEM.
CheNER: a tool for the identification of chemical entities and their classes in biomedical literature
Authors: Usié Anabel , Cruz Joaquim , Comas Jorge , Solsona Francesc , Alves Rui
Published: June 2015

Background

Small chemical molecules regulate biological processes at the molecular level. Those molecules are often involved in causing or treating pathological states. Automatically identifying such molecules in biomedical text is difficult due to both, the diverse morphology of chemical names and the alternative types of nomenclature that are simultaneously used to describe them. To address these issues, the last BioCreAtIvE challenge proposed a CHEMDNER task, which is a Named Entity Recognition (NER) challenge that aims at labelling different types of chemical names in biomedical text.

Methods

To address this challenge we tested various approaches to recognizing chemical entities in biomedical documents. These approaches range from linear Conditional Random Fields (CRFs) to a combination of CRFs with regular expression and dictionary matching, followed by a post-processing step to tag those chemical names in a corpus of Medline abstracts. We named our best performing systems CheNER.

Results

We evaluate the performance of the various approaches using the F-score statistics. Higher F-scores indicate better performance. The highest F-score we obtain in identifying unique chemical entities is 72.88%. The highest F-score we obtain in identifying all chemical entities is 73.07%. We also evaluate the F-Score of combining our system with ChemSpot, and find an increase from 72.88% to 73.83%.

Conclusions

CheNER presents a valid alternative for automated annotation of chemical entities in biomedical documents. In addition, CheNER may be used to derive new features to train newer methods for tagging chemical entities. CheNER can be downloaded from http://metres.udl.cat and included in text annotation pipelines.
CHEMDNER system with mixed conditional random fields and multi-scale word clustering
Authors: Lu Yanan , Ji Donghong , Yao Xiaoyuan , Wei Xiaomei , Liang Xiaohui
Published: June 2015

Background

The chemical compound and drug name recognition plays an important role in chemical text mining, and it is the basis for automatic relation extraction and event identification in chemical information processing. So a high-performance named entity recognition system for chemical compound and drug names is necessary.

Methods

We developed a CHEMDNER system based on mixed conditional random fields (CRF) with word clustering for chemical compound and drug name recognition. For the word clustering, we used Brown's hierarchical algorithm and Skip-gram model based on deep learning with massive PubMed articles including titles and abstracts.

Results

This system achieved the highest F-score of 88.20% for the CDI task and the second highest F-score of 87.11% for the CEM task in BioCreative IV. The performance was further improved by multi-scale clustering based on deep learning, achieving the F-score of 88.71% for CDI and 88.06% for CEM.

Conclusions

The mixed CRF model represents both the internal complexity and external contexts of the entities, and the model is integrated with word clustering to capture domain knowledge with PubMed articles including titles and abstracts. The domain knowledge helps to ensure the performance of the entity recognition, even without fine-grained linguistic features and manually designed rules.
Incorporating domain knowledge in chemical and biomedical named entity recognition with word representations
Authors: Munkhdalai Tsendsuren , Li Meijing , Batsuren Khuyagbaatar , Park Hyeon Ah , Choi Nak Hyeon , Ryu Keun Ho
Published: June 2015

Background

Chemical and biomedical Named Entity Recognition (NER) is an essential prerequisite task before effective text mining can begin for biochemical-text data. Exploiting unlabeled text data to leverage system performance has been an active and challenging research topic in text mining due to the recent growth in the amount of biomedical literature.

We present a semi-supervised learning method that efficiently exploits unlabeled data in order to incorporate domain knowledge into a named entity recognition model and to leverage system performance. The proposed method includes Natural Language Processing (NLP) tasks for text preprocessing, learning word representation features from a large amount of text data for feature extraction, and conditional random fields for token classification. Other than the free text in the domain, the proposed method does not rely on any lexicon nor any dictionary in order to keep the system applicable to other NER tasks in bio-text data.

Results

We extended BANNER, a biomedical NER system, with the proposed method. This yields an integrated system that can be applied to chemical and drug NER or biomedical NER. We call our branch of the BANNER system BANNER-CHEMDNER, which is scalable over millions of documents, processing about 530 documents per minute, is configurable via XML, and can be plugged into other systems by using the BANNER Unstructured Information Management Architecture (UIMA) interface.

BANNER-CHEMDNER achieved an 85.68% and an 86.47% F-measure on the testing sets of CHEMDNER Chemical Entity Mention (CEM) and Chemical Document Indexing (CDI) subtasks, respectively, and achieved an 87.04% F-measure on the official testing set of the BioCreative II gene mention task, showing remarkable performance in both chemical and biomedical NER. BANNER-CHEMDNER system is available at: https://bitbucket.org/tsendeemts/banner-chemdner.
What is the effect of phasing out long-chain per- and polyfluoroalkyl substances on the concentrations of perfluoroalkyl acids and their precursors in the environment? A systematic review protocol
Authors: Land Magnus , de Wit Cynthia A , Cousins Ian T , Herzke Dorte , Johansson Jana , Martin Jonathan W
Published: June 2015

Background

There is a growing concern in Sweden and elsewhere that continued emissions of per- and polyfluoroalkyl substances (PFASs) may cause environmental as well as human health effects. PFASs are a broad class of man-made substances that have been produced and used in both commercial products and industrial processes for more than 60 years. Although the production and use of some PFASs has been phased-out in some parts of the world, it is not known what effect these actions to date have had on PFAS concentrations in the environment. Owing to the wide diversity of PFASs, it is difficult to generalize their properties, environmental fate and production histories. However, the strength and stability of the C-F bond renders the perfluoroalkyl moieties resistant to heat and environmental degradation. Several PFASs are now occurring even in very remote areas in large parts of the world, but the environmental transport and fate of substances within this group is not well understood. A systematic review may be able to determine whether the concentrations of these substances in different environments are changing in any particular direction with time, and whether the phase-outs have had any effects on the concentration trends.

Methods

Searches for primary research studies reporting on temporal variations of PFAS concentrations in the environment will be performed in the scientific literature as well as in other reports. Relevant samples include both abiotic and biological samples including humans. No particular time, document type, language or geographical constraints will be applied. Two authors will screen all retrieved articles. Double screening of about 10% of the articles will be performed by all authors at both title/abstract and full-text levels. Kappa tests will be used to test if the screening is consistent. Relevant articles will be critically appraised by four authors (double checking of 25% of the articles). Quality assessment will focus on selection bias, dating of samples, sample integrity and analytical procedures. Data synthesis will be based on statistical analysis of temporal concentration trends.
Lactococcus garvieae: a small bacteria and a big data world
Authors: López-Campos Guillermo , Aguado-Urda Mónica , Blanco María Mar , Gibello Alicia , Cutuli María Teresa , López-Alonso Victoria , Martín-Sánchez Fernando , Fernández-Garayzábal José F
Published: June 2015

Objective

To describe the importance of bioinformatics tools to analyze the big data yielded from new "omics" generation-methods, with the aim of unraveling the biology of the pathogen bacteria Lactococcus garvieae.

Methods

The paper provides the vision of the large volume of data generated from genome sequences, gene expression profiles by microarrays and other experimental methods that require biomedical informatics methods for management and analysis.

Results

The use of biomedical informatics methods improves the analysis of big data in order to obtain a comprehensive characterization and understanding of the biology of pathogenic organisms, such as L. garvieae.

Conclusions

The "Big Data" concepts of high volume, veracity and variety are nowadays part of the research in microbiology associated with the use of multiple methods in the "omic" era. The use of biomedical informatics methods is a requisite necessary to improve the analysis of these data.
Genetically engineering encapsulin protein cage nanoparticle as a SCC-7 cell targeting optical nanoprobe
Authors: Moon Hyojin , Lee Jisu , Kim Hansol , Heo Somin , Min Junseon , Kang Sebyung
Published: June 2015

Background

Protein cage nanoparticles are promising nanoplatform candidates for efficient delivery systems of diagnostics and/or therapeutics because of their uniform size and structure as well as high biocompatibility and biodegradability. Encapsulin protein cage nanoparticle is used to develop a cell-specific targeting optical nanoprobe.

Results

FcBPs are genetically inserted and successfully displayed on the surface of encapsulin to form FcBP-encapsulin. Selectively binding of FcBP-encapsulin to SCC-7 is visualized with fluorescent microscopy.

Conclusions

Encapsulin protein cage nanoparticle is robust enough to maintain their structure at high temperature and easily acquires multifunctions on demand through the combination of genetic and chemical modifications.
Simple clinical indicators for early psoriatic arthritis detection
Authors: Caso Francesco , Costa Luisa , Atteno Mariangela , Del Puente Antonio , Cantarini Luca , Lubrano Ennio , Scarpa Raffaele
Published: June 2015

Background

Diagnosis of psoriatic arthritis (PsA), in a period of 12 months from the onset of the first articular episode, permits of identifying the early form defined as “early PsA”. The recognition of the disease in this phase leads to better outcome.

The aim of this study was to identify peculiar clinical and/or laboratory findings that could be useful for the diagnosis of “early PsA”.

Findings

Thirty-five patients with early onset of arthritis were observed. The following data were collected for each patient: family and personal history, physical examination, tender and swollen joint counts (TJC, SJC), tender entheseal count, presence of dactylitis and low back pain (LBP), and laboratory tests.

Among the 35 total patients, 24 showed skin and/or nail psoriasis or a family history of psoriasis.

The remaining 11 patients showed absence of concomitant or previous psoriasis and/or familiarity for psoriasis. The comparison between the two groups showed that patients with psoriasis had a significant presence of LBP, dactylitis and enthesitis than patients with psoriasis.

Conclusions

The study confirms that the distinctive clinical findings of PsA is psoriasis, but also LBP, dactylitis and enthesitis have a relevant role in early identification. A low number of SJC and TJC are frequently observed in early phases of PsA than in other forms of early arthritis. These aspects could be mostly helpful when psoriasis is not detected or can follow arthritis in absence of familiar positivity, making difficult PsA diagnosis.

In conclusion, careful medical history, clinical examination and first-level laboratory investigations are useful to characterize early phases of PsA.
Isolation and functional characterization of novel biosurfactant produced by Enterococcus faecium
Authors: Sharma Deepansh , Saharan Baljeet Singh , Chauhan Nikhil , Procha Suresh , Lal Sohan
Published: June 2015

The objective of the present study was to isolate the biosurfactant (BS) producing lactic acid bacteria (LAB) from traditional fermented food (buttermilk) and its functional and structural characterization. BS isolated from strain MRTL9 reduced surface tension from 72.0 to 40.2 mN m-1. The critical micelle concentration (CMC) of BS was 2.25 mg ml-1 with emulsification efficiency (E24) after 24 h of 64% against kerosene oil. The cell bound BS was partially purified by silica gel column chromatography and found as glycolipid. The gas chromatography and mass spectroscopy data revealed the fatty acid as hexadecanoic acid. Xylose was determined as hydrophilic moiety. The BS was found to be stable to pH changes over a range of 4.0-12.0, being most effective at pH 7 and showed no apparent loss of surface tension and emulsification efficiency after heat treatment at 120°C for 15 min. The outcomes of cellular toxicity showed lower toxicity of BS in comparison to SDS and rhamnolipids. Current study confirmed the preventive anti-adhesion activity of BS. These amphiphilic molecules, interferes with the microbial adhesion and found to be least cytotoxic with cellular compatibility with mouse fibroblasts cells.
Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude
Authors: Zhu Hai-tao , Bian Chen , Yuan Ji-chao , Liao Xiao-jun , Liu Wei , Zhu Gang , Feng Hua , Lin Jiang-kai
Published: June 2015

Introduction

Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH.

Methods

Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH.

Results

High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated.

Conclusions

The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.
Identification of two novel mammographic density loci at 6Q25.1
Authors: Brand Judith S , Li Jingmei , Humphreys Keith , Karlsson Robert , Eriksson Mikael , Ivansson Emma , Hall Per , Czene Kamila
Published: June 2015

Introduction

Mammographic density (MD) is a strong heritable and intermediate phenotype for breast cancer, but much of its genetic variation remains unexplained. We performed a large-scale genetic association study including 8,419 women of European ancestry to identify MD loci.

Methods

Participants of three Swedish studies were genotyped on a custom Illumina iSelect genotyping array and percent and absolute mammographic density were ascertained using semiautomated and fully automated methods from film and digital mammograms. Linear regression analysis was used to test for SNP-MD associations, adjusting for age, body mass index, menopausal status and six principal components. Meta-analyses were performed by combining P values taking sample size, study-specific inflation factor and direction of effect into account.

Results

Genome-wide significant associations were observed for two previously identified loci: ZNF365 (rs10995194, P = 2.3 × 10−8 for percent MD and P = 8.7 × 10−9 for absolute MD) and AREG (rs10034692, P = 6.7 × 10−9 for absolute MD). In addition, we found evidence of association for two variants at 6q25.1, both of which are known breast cancer susceptibility loci: rs9485370 in the TAB2 gene (P = 4.8 × 10−9 for percent MD and P = 2.5 × 10−8 for absolute MD) and rs60705924 in the CCDC170/ESR1 region (P = 2.2 × 10−8 for absolute MD). Both regions have been implicated in estrogen receptor signaling with TAB2 being a potential regulator of tamoxifen response.

Conclusions

We identified two novel MD loci at 6q25.1. These findings underscore the importance of 6q25.1 as a susceptibility region and provide more insight into the mechanisms through which MD influences breast cancer risk.
Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1
Authors: Seitz Tina , Stalmann Robert , Dalila Nawar , Chen Jiayin , Pojar Sherin , Dos Santos Pereira Joao N. , Krätzner Ralph , Brockmöller Jürgen , Tzvetkov Mladen V.
Published: June 2015

Background

The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans.

Methods

We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity.

Results

We identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima’s D = −1.64, P < 0.01).

Conclusions

Comprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1.
The class of $(\alpha,\psi)$-type contractions in b-metric spaces and fixed point theorems
Authors: Samet Bessem
Published: June 2015

We study the existence and uniqueness of fixed points for self-operators defined in a b-metric space and belonging to the class of $(\alpha,\psi)$
(
α
,
ψ
)
-type contraction mappings. The obtained results generalize and unify several existing fixed point theorems in the literature.
Curcumin as a double-edged sword for stem cells: dose, time and cell type-specific responses to curcumin
Authors: Attari Fatemeh , Zahmatkesh Maryam , Aligholi Hadi , Mehr Shahram Ejtemaei , Sharifzadeh Mohammad , Gorji Ali , Mokhtari Tahmineh , Khaksarian Mojtaba , Hassanzadeh Gholamreza
Published: June 2015

Background

The beneficial effects of curcumin which includes its antioxidant, anti-inflammatory and cancer chemo-preventive properties have been identified. Little information is available regarding the optimal dose and treatment periods of curcumin on the proliferation rate of different sources of stem cells.

Methods

In this study, the effect of various concentrations of curcumin on the survival and proliferation of two types of outstanding stem cells which includes bone marrow stem cells (BMSCs) and adult rat neural stem/progenitor cells (NS/PCs) at different time points was investigated. BMSCs were isolated from bilateral femora and tibias of adult Wistar rats. NS/PCs were obtained from subventricular zone of adult Wistar rat brain. The curcumin (0.1, 0.5, 1, 5 and 10 μM/L) was added into a culture medium for 48 or 72 h. Fluorescent density of 5-bromo-2′-deoxyuridine (Brdu)-positive cells was considered as proliferation index. In addition, cell viability was assessed by MTT assay.

Results

Treatment of BMSCs with curcumin after 48 h, increased cell survival and proliferation in a dose-dependent manner. However, it had no effect on NSCs proliferation except a toxic effect in the concentration of 10 μM of curcumin. After a 72 h treatment period, BMSCs and NS/PCs survived and proliferated with low doses of curcumin. However, high doses of curcumin administered for 72 h showed toxic effects on both stem cells.

Conclusions

These findings suggest that curcumin survival and proliferative effects depend on its concentration, treatment period and the type of stem cells. Appropriate application of these results may be helpful in the outcome of combination therapy of stem cells and curcumin.
Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential of human urine-derived stem cells
Authors: Guan Junjie , Zhang Jieyuan , Zhu Zhenzhong , Niu Xin , Guo Shangchun , Wang Yang , Zhang Changqing
Published: June 2015

Introduction

Urine-derived stem cells (USCs) have the ability to differentiate into osteogenic lineage. Previous studies have raised the possibility that USCs could be used for bone repair. To harness the power of USCs in promoting bone regeneration, methods must be developed to induce USCs to osteogenic lineage efficiently. The present study investigates the effect of lentivirus-encoded bone morphogenetic protein 2 (BMP2) gene transduction on the osteogenic potential of USCs.

Methods

USCs were isolated from voided urine and transduced with Lentiviral vector encoding BMP2. An in vitro study was performed to detect Lentiviral-BMP2 transduced USCs differentiated towards osteogenic lineage. Furthermore, Lentiviral-BMP2 transduced USCs were transplanted in vivo to examine the ectopic bone formation ability. After six weeks, retrieval samples were obtained for immunostaining and histological analysis.

Results

The results showed that the transduction efficiencies were over 90%, and transduced USCs had high expression levels of the BMP2 gene and secreted BMP2 protein. Alkaline activity and mineral deposition staining demonstrated that transduced USCs differentiate into osteogenic lineages without the addition of osteogenic supplements. Transduced USCs also showed high expression of bone-related markers, including runt-related protein-2 (Runx2) and osteocalcin (OCN), confirming this lentiviral-BMP2 construct provides sufficient stimuli for osteogenic differentiation. Histological analysis indicated that the transduced USCs induced robust new bone formation in nude mice. Six weeks after transplantation, human derived cells were observed to participate in bone formation.

Conclusions

These results demonstrate that BMP2 gene transduction provides an effective method to enhance the osteogenic potential of USCs.
The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity
Authors: Cui Li-li , Kerkelä Erja , Bakreen Abdulhameed , Nitzsche Franziska , Andrzejewska Anna , Nowakowski Adam , Janowski Miroslaw , Walczak Piotr , Boltze Johannes , Lukomska Barbara , Jolkkonen Jukka
Published: June 2015

Introduction

Intra-arterial cell infusion is an efficient delivery route with which to target organs such as the ischemic brain. However, adverse events including microembolisms and decreased cerebral blood flow were recently reported after intra-arterial cell delivery in rodent models, raising safety concerns. We tested the hypothesis that cell dose, infusion volume, and velocity would be related to the severity of complications after intra-arterial cell delivery.

Methods

In this study, 38 rats were subjected to a sham middle cerebral artery occlusion (sham-MCAO) procedure before being infused with allogeneic bone-marrow mesenchymal stem cells at different cell doses (0 to 1.0 × 106), infusion volumes (0.5 to 1.0 ml), and infusion times (3 to 6 minutes). An additional group (n = 4) was infused with 1.0 × 106 cells labeled with iron oxide for in vivo tracking of cells. Cells were infused through the external carotid artery under laser Doppler flowmetry monitoring 48 hours after sham-MCAO. Magnetic resonance imaging (MRI) was performed 24 hours after cell infusion to reveal cerebral embolisms or hemorrhage. Limb placing, cylinder, and open field tests were conducted to assess sensorimotor functions before the rats were perfused for histology.

Results

A cell dose-related reduction in cerebral blood flow was noted, as well as an increase in embolic events and concomitant lesion size, and sensorimotor impairment. In addition, a low infusion velocity (0.5 ml/6 minutes) was associated with high rate of complications. Lesions on MRI were confirmed with histology and corresponded to necrotic cell loss and blood-brain barrier leakage.

Conclusions

Particularly cell dose but also infusion velocity contribute to complications encountered after intra-arterial cell transplantation. This should be considered before planning efficacy studies in rats and, potentially, in patients with stroke.
Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice
Authors: Hu Guo-wen , Li Qing , Niu Xin , Hu Bin , Liu Juan , Zhou Shu-min , Guo Shang-chun , Lang Hai-li , Zhang Chang-qing , Wang Yang , Deng Zhi-feng
Published: June 2015

Introduction

‘Patient-specific’ induced pluripotent stem cells (iPSCs) are attractive because they can generate abundant cells without the risk of immune rejection for cell therapy. Studies have shown that iPSC-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effects. Recently, most studies indicate that stem cells exert their therapeutic effect mainly through a paracrine mechanism other than transdifferentiation, and exosomes have emerged as an important paracrine factor for stem cells to reprogram injured cells. The objective of this study was to evaluate whether exosomes derived from iMSCs (iMSCs-Exo) possess the ability to attenuate limb ischemia and promote angiogenesis after transplantation into limbs of mice with femoral artery excision.

Methods

Human iPSCs (iPS-S-01, C1P33, and PCKDSF001C1) were used to differentiate into iMSCs in a modified one-step method. iMSCs were characterized by flow cytometry and multipotent differentiation potential analysis. Ultrafiltration combined with a purification method was used to isolate iMSCs-Exo, and transmission electron microscopy and Western blotting were used to identify iMSCs-Exo. After establishment of mouse hind-limb ischemia with excision of femoral artery and iMSCs-Exo injection, blood perfusion was monitored at days 0, 7, 14, and 21; microvessel density in ischemic muscle was also analyzed. In vitro migration, proliferation, and tube formation experiments were used to analyze the ability of pro-angiogenesis in iMSCs-Exo, and quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were used to identify expression levels of angiogenesis-related molecules in human umbilical vein endothelial cells (HUVECs) after being cultured with iMSCs-Exo.

Results

iPSCs were efficiently induced into iMSC- with MSC-positive and -negative surface antigens and osteogenesis, adipogenesis, and chondrogenesis differentiation potential. iMSCs-Exo with a diameter of 57 ± 11 nm and expressed CD63, CD81, and CD9. Intramuscular injection of iMSCs-Exo markedly enhanced microvessel density and blood perfusion in mouse ischemic limbs, consistent with an attenuation of ischemic injury. In addition, iMSCs-Exo could activate angiogenesis-related molecule expression and promote HUVEC migration, proliferation, and tube formation.

Conclusion

Implanted iMSCs-Exo was able to protect limbs from ischemic injury via the promotion of angiogenesis, which indicated that iMSCs-Exo may be a novel therapeutic approach in the treatment of ischemic diseases.