bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-24-3p/FGFR3 Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression
Authors: Jing Pengyu , Zhao Nan , Xie Nianlin , Ye Mingxiang , Zhang Yong , Zhang Zhipei , Li Mengyang , Lai Xiaofeng , Zhang Jian , Gu Zhongping
Published: April 2018

Our previous studies showed that Fibroblast growth factor receptor 3 (FGFR3) contributed to cell growth in lung cancer. However, the correlation between FGFR3 and tumor progression, coupled with the underlying mechanisms, are not fully understood. The clinical significance of FGFR3 was determined in two cohorts of clinical samples (n=22, n=78). A panel of biochemical assays and functional experiments was utilized to elucidate the underlying mechanisms and effects of FGFR3 and miR-24-3p on lung adenocarcinoma progression. Upregulated FGFR3 expression indicated an adverse prognosis for lung adenocarcinoma individuals and promoted metastatic potential of lung adenocarcinoma cells. Owing to the direct regulation towards FGFR3, miR-24-3p could interfere with the potential of proliferation, migration, and invasion in lung adenocarcinoma, following variations of EMT-related protein expression. As a significant marker of EMT, E-cadherin was negatively correlated with FGFR3, of which ectopic overexpression could neutralize the antitumour effects of miR-24-3p and reverse its regulatory effects on EMT markers. Taken together, these findings define a novel insight into the miR-24-3p/FGFR3 signaling axis in regulating lung adenocarcinoma progression and suggest that targeting the miR-24-3p/FGFR3 axis could be an effective and efficient way to prevent tumor progression.
Transcatheter versus Surgical Aortic Valve Replacement after Previous Cardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Shehada Sharaf-Eldin , Elhmidi Yacine , Öztürk Öznur , Kasel Markus , Frangieh Antonio H. , Mourad Fanar , Benedik Jaroslav , El Bahi Jaafar , El Gabry Mohamed , Thielmann Matthias , Jakob Heinz , Wendt Daniel
Published: April 2018

Aim. Aortic valve replacement (AVR) in patients with prior cardiac surgery might be challenging. Transcatheter aortic valve replacement (TAVR) offers a promising alternative in such patients. We therefore aimed at comparing the outcomes of patients with aortic valve diseases undergoing TAVR versus those undergoing surgical AVR (SAVR) after previous cardiac surgery. Methods and Results. MEDLINE, EMBASE, and the Cochrane Central Register were searched. Seven relevant studies were identified, published between 01/2011 and 12/2015, enrolling a total of 1148 patients with prior cardiac surgery (97.6% prior CABG): 49.2% underwent TAVR, whereas 50.8% underwent SAVR. Incidence of stroke (3.8 versus 7.9%, p=0.04) and major bleeding (8.3 versus 15.3%, p=0.04) was significantly lower in the TAVR group. Incidence of mild/severe paravalvular leakage (14.4/10.9 versus 0%, p<0.0001) and pacemaker implantation (11.3 versus 3.9%, p=0.01) was significantly higher in the TAVR group. There were no significant differences in the incidence of acute kidney injury (9.7 versus 8.7%, p=0.99), major adverse cardiovascular events (8.7 versus 12.3%, p=0.21), 30-day mortality (5.1 versus 5.5%, p=0.7), or 1-year mortality (11.6 versus 11.8%, p=0.97) between the TAVR and SAVR group. Conclusions. TAVR as a redo procedure offers a safe alternative for patients presenting with aortic valve diseases after previous cardiac surgery especially those with prior CABG.
Microscopic Simulation-Based High Occupancy Vehicle Lane Safety and Operation Assessment: A Case Study
Authors: Li Chao , Karimi Mohammad , Alecsandru Ciprian
Published: April 2018

This study proposes two general alternative designs to enhance the operation and safety of High Occupancy Vehicle (HOV) lanes at junctions with bus terminals or parking lots. A series of analysis tools, including microscopic simulation, video-based vehicle tracking technique, and Surrogate Safety Assessment Model (SSAM), are applied to model and test the safety and operational efficiency of an HOV road segment near a bus terminal in Québec as a case study. A metaheuristic optimization algorithm (i.e., Whale Optimization Algorithm) is employed to calibrate the microscopic model while deviation from the observed headway distribution is considered as a cost function. The results indicate that this type of HOV configurations exhibits significant safety problems (high number of crossing conflicts) and operational issues (high value of total delay) due to the terminal-bound buses that frequently need to travel across the main road. It is shown that the proposed alternative geometry design efficiently ameliorates the traffic conflicts issues. In addition, the alternative control design scheme significantly reduces the public transit delay. It is expected that this methodology can be applied to other reserved lane configurations similar to the investigated case study.
Outsourcing Set Intersection Computation Based on Bloom Filter for Privacy Preservation in Multimedia Processing
Authors: Zhu Hongliang , Chen Meiqi , Sun Maohua , Liao Xin , Hu Lei
Published: April 2018

With the development of cloud computing, the advantages of low cost and high computation ability meet the demands of complicated computation of multimedia processing. Outsourcing computation of cloud could enable users with limited computing resources to store and process distributed multimedia application data without installing multimedia application software in local computer terminals, but the main problem is how to protect the security of user data in untrusted public cloud services. In recent years, the privacy-preserving outsourcing computation is one of the most common methods to solve the security problems of cloud computing. However, the existing computation cannot meet the needs for the large number of nodes and the dynamic topologies. In this paper, we introduce a novel privacy-preserving outsourcing computation method which combines GM homomorphic encryption scheme and Bloom filter together to solve this problem and propose a new privacy-preserving outsourcing set intersection computation protocol. Results show that the new protocol resolves the privacy-preserving outsourcing set intersection computation problem without increasing the complexity and the false positive probability. Besides, the number of participants, the size of input secret sets, and the online time of participants are not limited.
A Framework for Exploiting Internet of Things for Context-Aware Trust-Based Personalized Services
Authors: Otebolaku Abayomi , Lee Gyu Myoung
Published: April 2018

In the last years, we have witnessed the introduction of the Internet of Things (IoT) as an integral part of the Internet with billions of interconnected and addressable everyday objects. On one hand, these objects generate a massive volume of data that can be exploited to gain useful insights into our day-to-day needs. On the other hand, context-aware recommender systems (CARSs) are intelligent systems that assist users to make service consumption choices that satisfy their preferences based on their contextual situations. However, one of the key challenges facing the development and deployment of CARSs is the lack of functionality for providing dynamic and reliable context information required by the recommendation decision process. Thus, data obtained from IoT objects and other sources can be exploited to build CARSs that satisfy users’ preferences, improve quality of experience, and boost recommendation accuracy. This article describes various components of a conceptual IoT-based framework for context-aware personalized recommendations. The framework addresses the weakness whereby CARSs rely on static and limited contexts from user’s mobile phone by providing additional components for reliable and dynamic context information, using IoT context sources. The core of the framework consists of a context classification and reasoning management and a dynamic user profile model, incorporating trust to improve the accuracy of context-aware personalized recommendations. Experimental evaluations show that incorporating context and trust into personalized recommendation process can improve accuracy.
Tile-Based Semisupervised Classification of Large-Scale VHR Remote Sensing Images
Authors: Alhichri Haikel , Othman Essam , Zuair Mansour , Ammour Nassim , Bazi Yakoub
Published: April 2018

This paper deals with the problem of the classification of large-scale very high-resolution (VHR) remote sensing (RS) images in a semisupervised scenario, where we have a limited training set (less than ten training samples per class). Typical pixel-based classification methods are unfeasible for large-scale VHR images. Thus, as a practical and efficient solution, we propose to subdivide the large image into a grid of tiles and then classify the tiles instead of classifying pixels. Our proposed method uses the power of a pretrained convolutional neural network (CNN) to first extract descriptive features from each tile. Next, a neural network classifier (composed of 2 fully connected layers) is trained in a semisupervised fashion and used to classify all remaining tiles in the image. This basically presents a coarse classification of the image, which is sufficient for many RS application. The second contribution deals with the employment of the semisupervised learning to improve the classification accuracy. We present a novel semisupervised approach which exploits both the spectral and spatial relationships embedded in the remaining unlabelled tiles. In particular, we embed a spectral graph Laplacian in the hidden layer of the neural network. In addition, we apply regularization of the output labels using a spatial graph Laplacian and the random Walker algorithm. Experimental results obtained by testing the method on two large-scale images acquired by the IKONOS2 sensor reveal promising capabilities of this method in terms of classification accuracy even with less than ten training samples per class.
MicroRNA-1 Regulates the Differentiation of Adipose-Derived Stem Cells into Cardiomyocyte-Like Cells
Authors: Chen Can , Yan Quanxiang , Yan Yiguang , Ma Mudi , He Yuan , Shui Xiaorong , Yang Zhigang , Lan Xiaozhong , Tang Yaoliang , Lei Wei
Published: April 2018

Stem cell transplantation is one of most valuable methods in the treatment of myocardial infarction, and adipose-derived stem cells (ASCs) are becoming a hot topic in medical research. Previous studies have shown that ASCs can be differentiated into cardiomyocyte-like cells, but the efficiency and survival rates are low. We investigated the role and mechanism of microRNA-1 (miR-1) in the differentiation of ASCs into cardiomyocyte-like cells. ASCs and cardiomyocytes were isolated from neonatal rats. We constructed lentivirus for overexpressing miR-1 and used DAPT, an antagonist of the Notch1 pathway, for in vitro analyses. We performed cocultures with ASCs and cardiomyocytes. The differentiation efficiency of ASCs was detected by cell-specific surface antigens. Our results showed that miR-1 can promote the expression of Notch1 and reduce the expression of Hes1, a Notch pathway factor, and overexpression of miR-1 can promote the differentiation of ASCs into cardiomyocyte-like cells, which may occur by regulating Notch1 and Hes1.
Modeling Creep Fracture in Rock by Using Kelvin Discretized Virtual Internal Bond
Authors: He Wangyang , Zhang Zhennan
Published: April 2018

Discretized virtual internal bond (DVIB) is a lattice model, which is composed of bond cells. Each bond cell has a finite number of bonds. The DVIB is used to model the creep fracture. It is done by introducing a viscous bond to the original hyperelastic DVIB. The hyperelastic bond is parallel coupled with a viscous bond together, forming a hybrid hyperelastic‐Kelvin bond. The hyperelastic bond reflects the microfracture mechanism, whereas the viscous bond reflects the creep mechanism. Based on this hyperelastic‐Kelvin bond, the constitutive relation of a cell is derived. The microbond parameters are calibrated based on the ideal cell approach. The simulation results suggest that this method can represent the typical features of creep and can simulate the creep fracture. The merit of this method lies in that the complicated 3D macrocreep problem is reduced to the 1D microbond creep problem. No creep law is previously derived. The macrocreep fracture behavior is the natural response of the assembly of the micro hyperelastic‐Kelvin bonds.
A Low Computational Complexity Scheme for the Prediction of Intrinsically Disordered Protein Regions
Authors: He Hao , Zhao Jiaxiang
Published: April 2018

We employ the Rayleigh entropy maximization to develop a novel IDP scheme which requires computing only five features for each residue of a protein sequence, that is, the Shannon entropy, topological entropy, and the weighted average values of three propensities. Furthermore, our scheme is a linear classification method and hence requires computing simpler decision curves which are more robust as well as using fewer learning samples to compute. The simulation results of our scheme as well as some existing schemes demonstrate its effectiveness.
Dynamic Modeling and Interactive Performance of PARM: A Parallel Upper-Limb Rehabilitation Robot Using Impedance Control for Patients after Stroke
Authors: Guang Hui , Ji Linhong , Shi Yingying , Misgeld Berno J. E.
Published: April 2018

The robot-assisted therapy has been demonstrated to be effective in the improvements of limb function and even activities of daily living for patients after stroke. This paper presents an interactive upper-limb rehabilitation robot with a parallel mechanism and an isometric screen embedded in the platform to display trajectories. In the dynamic modeling for impedance control, the effects of friction and inertia are reduced by introducing the principle of virtual work and derivative of Jacobian matrix. To achieve the assist-as-needed impedance control for arbitrary trajectories, the strategy based on orthogonal deviations is proposed. Simulations and experiments were performed to validate the dynamic modeling and impedance control. Besides, to investigate the influence of the impedance in practice, a subject participated in experiments and performed two types of movements with the robot, that is, rectilinear and circular movements, under four conditions, that is, with/without resistance or impedance, respectively. The results showed that the impedance and resistance affected both mean absolute error and standard deviation of movements and also demonstrated the significant differences between movements with/without impedance and resistance (p<0.001). Furthermore, the error patterns were discussed, which suggested that the impedance environment was capable of alleviating movement deviations by compensating the synergetic inadequacy between the shoulder and elbow joints.
Proteomic Analysis of Hippocampus and Cortex in Streptozotocin-Induced Diabetic Model Mice Showing Dementia
Authors: Matsuura Kenji , Otani Mieko , Takano Masaoki , Kadoyama Keiichi , Matsuyama Shogo
Published: April 2018

Aim. Diabetes with its associated hyperglycemia induces various type of peripheral damage and also impairs the central nervous system (CNS). This study is aimed at clarifying the precise mechanism of diabetes-induced dementia as an impairment of CNS. Methods. The proteomic analysis of the hippocampus and cortex in streptozotocin- (STZ-) treated mouse diabetic model showing dementia was performed using two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (n=3/group). Results. Significant changes in the expression of 32 proteins and 7 phosphoproteins were observed in the hippocampus and cortex. These identified proteins and phosphoproteins could be functionally classified as cytoskeletal protein, oxidoreductase, protein deubiquitination, energy metabolism, GTPase activation, heme binding, hydrolase, iron storage, neurotransmitter release, protease inhibitor, transcription, glycolysis, antiapoptosis, calcium ion binding, heme metabolic process, protein degradation, vesicular transport, and unknown in the hippocampus or cortex. Additionally, Western blotting validated the changes in translationally controlled tumor protein, ATP-specific succinyl-CoA synthetase beta subunit, and gamma-enolase isoform 1. Conclusions. These findings showed that STZ-induced diabetes changed the expression of proteins and phosphoproteins in the hippocampus and cortex. We propose that alterations in expression levels of these proteins play an important role in diabetes-induced dementia.
Design of a Suspended Stripline Narrow Bandpass Filter with Ultrawideband Harmonic Suppression
Authors: Park Ju Seong , Mohyuddin Wahab , Choi Hyun Chul , Kim Kang Wook
Published: April 2018

A design method of narrow bandpass filters (NBPFs) of 4–6% bandwidth with ultrawideband suppression of harmonic passbands, utilizing two cascaded step impedance resonators (SIRs) in a suspended stripline, is proposed in this paper. The proposed design utilized the characteristics of a suspended stripline, which provides a much higher characteristic impedance ratio as compared with that of the microstripline, enabling ultrawideband harmonic suppression. As an example of the NBPF, a filter with a passband center frequency f0 of 0.75 GHz and bandwidth of 5% was implemented and proved to suppress the harmonic passbands up to 13.5 f0. Since the proposed filter was implemented on the suspended stripline, the passband insertion loss was only −0.9 dB, which is low as compared with other previous designs. The proposed filter is a compact high-performance low-loss NBPF, which can be applicable to various wireless systems.
Anti-Inflammatory Effect of Columbianetin on Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
Authors: Lu Junying , Fang Keyong , Wang Shiji , Xiong Lingxin , Zhang Chao , Liu Zhongmin , Guan Xuewa , Zheng Ruipeng , Wang Guoqiang , Zheng Jingtong , Wang Fang
Published: April 2018

Dysregulated inflammation is increasingly considered as the main cause of many diseases on which NOD1/NF-κB pathway plays an important role. Columbianetin (CBT) is derived from the root of the Chinese herb Radix Angelicae Pubescentis for treating inflammatory diseases. Although the anti-inflammatory effect of CBT has been reported, its anti-inflammatory mechanism was poorly studied. In this study, we explored the anti-inflammatory pathway of CBT in lipopolysaccharide- (LPS-) stimulated human peripheral blood mononuclear cell (PBMC) model. Inflammatory cytokine production in culture supernatant was assessed using ELISA assay, and the possible anti-inflammatory pathway of CBT was screened using qPCR array and enrichment analysis with DAVID6.8. To further confirm the targeted pathway of CBT, we pretreated PBMC with the selective NOD1 inhibitor ML130 and then measured the protein levels of the pathway by Western blotting. The result showed that CBT effectively suppressed the expressions of TNF-α, IL-6, MCP-1, and IL-1β in a dose-dependent manner and significantly downregulated 19 out of 32 differentially expressed genes, most of which were involved in the NOD1/NF-κB pathway, and also showed that CBT remarkably inhibited LPS-induced NOD1, RIP2, and NF-κB activation. Furthermore, the inhibitory effects of CBT on NOD1/NF-κB pathways were blocked by ML130. These findings indicated that CBT inhibits the production of inflammatory cytokines induced by LPS involved in the downregulation of NOD1/NF-κB pathways.
Predictive Value of Four-Dimensional Strain Echocardiography for Adverse Cardiovascular Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention
Authors: Cai Wei , Dong Yan , Tian Lu , Cao Chun-Xia , Niu Xiu-Long , Liu Xin-Lin , Liu Jun-Xiang , Ji Wen-Jie , Zhang Zhuoli , Zhou Xin , Li Yu-Ming
Published: April 2018

Objectives: To investigate the predictive value of four-dimensional (4D) strain echocardiography for major adverse cardiovascular events (MACE) in ST-elevation acute myocardial infarction (STEMI) patients. Methods: Consecutive STEMI patients who underwent successful primary coronary interven tion (PCI) were enrolled and followed, with 2D and 4D strain echocardiography performed within 1 week after PCI. Results: Twenty-six first MACE were recorded in 81 patients who finished a ∼3.0 year follow-up. Compared with those without MACE, subjects with MACE were more likely to have anterior MI (73.08 vs. 38.18%, p = 0.003), significantly decreased 2D left ventricular ejection fraction (2DLVEF) and 4DLVEF (all p < 0.05), as well as an overtly compromised 4D strain parameters. The prediction models incorporating infarct location with either 2DLVEF or 4D strain parameters were then developed. Model comparisons revealed that the global area strain (GAS)-based model had the highest discriminative capacity (c statistics = 0.774) and was well calibrated for MACE. Additionally, the clinical utility of the GAS-based prediction model was verified by decision curve analysis showing a consistent positive and larger net benefit compared to the 2DLVEF-based model. Conclusions: Our data support a superiority of 4D strain echocardiography over conventional 2D echocardiography, especially GAS, for risk stratification in STEMI patients after successful primary PCI.
Identifying Risk Factors Shared by Bronchopulmonary Dysplasia, Severe Retinopathy, and Cystic Periventricular Leukomalacia in Very Preterm Infants for Targeted Intervention
Authors: Wang Lan-Wan , Lin Yung-Chieh , Wang Shan-Tair , Huang Chao-Ching ,   on behalf of the Taiwan Premature Infant Developmental Collaborative Study Group
Published: April 2018

Background: Bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (sROP), and cystic periventricular leukomalacia (cPVL) are 3 major morbidities with long-term neurodevelopmental impairments in preterm infants. Objective: To investigate the strength of associations and identify key risk factors shared by BPD, sROP, and cPVL for targeted intervention. Methods: We studied the Taiwanese very-preterm-infant registry data on 3,507 infants admitted to neonatal intensive care units and discharged at postmenstrual age ≥36 weeks between 2008 and 2013. Results: Of 3,507 infants, 1,497 presented with at least 1 morbidity (26 [1.7%], 386 [25.8%], and 1,085 [72.5%] exhibited 3, 2, and 1 morbidities, respectively). BPD was strongly associated with sROP (odds ratio 5.93; 95% confidence interval 5.02–7.03), followed by cPVL (2.08; 1.63–2.64), but sROP and cPVL were weakly associated (1.59; 1.17–2.13). Most risk factors contributed to BPD, which shared risk factors with sROP and cPVL. A birth weight of < 1,000 g, male sex, and prolonged mechanical ventilation (MV) were shared by BPD and sROP, and chorioamnionitis, severe respiratory distress syndrome, and prolonged MV specifically contributed to BPD and cPVL. Prolonged MV was the single risk factor common to BPD, sROP, and cPVL. Avoiding prolonged MV reduced the risk of having at least 1 of the 3 morbidities by 37%. Conclusions: BPD and sROP were most strongly associated. Most risk factors contributed to BPD, with differentially shared effects on sROP and cPVL. Prolonged MV was the only risk factor shared by all 3 morbidities, and avoiding it potentially reduced the risk of having at least 1 of them.
Platelet Additive Solutions: A Review of the Latest Developments and Their Clinical Implications
Authors: van der Meer Pieter F. , de Korte Dirk
Published: April 2018

Platelet additive solutions (PASs) have undergone many reformulations in order to further improve platelet storage. Studies of platelets stored in PAS-F (containing acetate, magnesium and potassium as key constituents) showed that platelets may be stored for 13 days with recovery and survival outcomes that are equal or even superior to 7-day stored platelets in plasma. Clinically, patients transfused with platelets in PAS have fewer allergic reactions, while for febrile reactions data are conflicting. Transfusion-related acute lung injury (TRALI) occurs less frequently if PAS is used for buffy coat-derived platelets, but for apheresis platelets there is no difference. For PAS-B and PAS-C, corrected count increments (CCIs) are lower than for platelets stored in plasma, but for PAS-E (like PAS-F also with acetate, magnesium and potassium but with additional phosphate), though limited data is available in the literature, the CCIs seem to be comparable to those observed for platelets in plasma. With platelets in PAS, there is an accumulated dilution effect of anticoagulant and PAS as well as a loss of number and function (due to storage and/or pathogen inactivation treatment) of platelets, of which it is not clear how this impacts clinical outcomes of patients undergoing massive transfusion. Worst-case in vitro studies, where the entire plasma fraction is replaced by supernatant of platelets in PAS, do show an effect on the ability of reconstituted whole blood to clot, but in a more realistic scenario, functional clotting parameters are not different. In this review, recent laboratory and clinical data are discussed, focusing on studies published after 2010.
Enhanced Pro-Inflammatory Response of Macrophages to Interleukin-33 in an Allergic Environment
Authors: Chia Noel , Kumar Rakesh K. , Foster Paul S. , Herbert Cristan
Published: April 2018

Background: Allergic asthma is common in childhood and is associated with a T-helper type 2 (Th2)-biased immunological response. Exacerbations of asthma are characterised by increased inflammation of the airways, which appears to be driven by interleukin (IL)-33 that can activate pulmonary macrophages. The Th2 cytokine environment of allergic asthma may contribute to exaggerated airway inflammation. Objectives: To test this, we assessed whether production of pro-inflammatory cytokines by IL-33-stimulated macrophages was enhanced in cells pre-treated with the key Th2 cytokines IL-4 and IL-13. We also investigated whether this was associated with altered expression of regulatory microRNAs (miRNAs). Methods: RAW264.7 cells cultured with IL-4 and IL-13 for 48 h were stimulated with IL-33 for 4 h. Pro-inflammatory mediators were assessed using quantitative real-time PCR (RT-PCR). Expression of miRNAs was assessed using microarrays and RT-PCR. In further experiments, we examined whether resolvin E1 (RvE1), which promotes the resolution of experimental asthmatic inflammation in vivo, could suppress the enhanced response by treating cells with RvE1 concurrently with IL-33 stimulation. Results: In cells pre-treated with IL-4 and IL-13, expression of mRNA for Ccl3, Ccl5, Ccl17, Ccl24, and Il1b in response to IL-33 stimulation was significantly increased. This was paralleled by up-regulated expression of miR-155-5p, a miRNA that is predicted to regulate several aspects of allergic inflammation. RvE1 suppressed the enhanced production of Ccl3, Ccl5, Ccl24, and Il1b. Conclusions: We conclude that IL-33-activated macrophages may contribute to the exaggerated airway inflammation in exacerbations of allergic asthma, and that RvE1 has potential as a therapeutic agent that targets macrophages.
Characteristics of Early Oropharyngeal Dysphagia in Patients with Multiple System Atrophy
Authors: Lee Hyun Haeng , Seo Han Gil , Kim Kwang-dong , Lee Seung Hak , Lee Woo Hyung , Oh Byung-Mo , Lee Woong-Woo , Kim Yoon , Kim Aryun , Kim Han-Joon , Jeon Beomseok , Han Tai Ryoon
Published: April 2018

Background/Aims: Dysphagia, a symptom of multiple system atrophy (MSA), is a major clinical concern. In this study, we investigate the characteristics of early oropharyngeal dysphagia (OD) in patients with MSA, and the differences between MSA subtypes. Methods: Patients enrolled in the study had previously been diagnosed with MSA at the clinic of the Department of Neurology, and had been referred for a videofluoroscopic swallowing study (VFSS), between 2005 and 2014, to check for dysphagia. The clinical characteristics and VFSS findings were analyzed and compared between the MSA subtypes. Results: This study enrolled 59 patients with MSA (24 men; 31 with MSA-P, 21 with MSA-C, and 7 with MSA-PC). Dysphagia symptoms were mostly limited to aspiration symptoms (90.48%) in patients with MSA-C, while difficulty in swallowing, increased mealtime, and drooling were frequent in those with MSA-P. The most common VFSS finding amongst patients was vallecular residue (n = 53, 89.8%), followed by penetration/aspiration (n = 40, 67.8%), and coating of the pharyngeal wall (n = 39, 66.1%). Comparison analysis between subtypes showed that apraxia and vallecular residue were more frequent and severe in MSA-P than in MSA-C (p = 0.033 and p = 0.010, respectively). Conclusion: Understanding early OD characteristics in patients with MSA and the differences between MSA subtypes could be helpful in managing dysphagia in patients with MSA. Several dysphagia symptoms similar to those of Parkinson disease were frequently observed in MSA-P, but not in MSA-C. A follow-up study is needed to elucidate the natural course of OD in MSA patients and the difference between MSA subtypes.
Temporal Trends of Stroke Epidemiology in Southern Sweden: A Population-Based Study on Stroke Incidence and Early Case-Fatality
Authors: Aked Joseph , Delavaran Hossein , Norrving Bo , Lindgren Arne
Published: April 2018

Background: Up-to-date epidemiological stroke studies are important for healthcare planning and evaluating prevention strategies. This population-based study investigates temporal trends in stroke incidence and case-fatality in southern Sweden. Methods: First-ever stroke cases in the local catchment area of Skåne University Hospital in Lund, Sweden, between March, 2015 and February, 2016, were included from several sources, including 2 prospective hospital-based registers, retrospective screening of primary care visits, and autopsy registers. Stroke incidence and 28-day case-fatality rates were compared with data from this area obtained through similar methodology between March, 2001 and February, 2002. Results: Altogether, 456 and 413 first-ever stroke patients were identified during the earlier and later time periods respectively. The age- and sex-standardized stroke incidence rates decreased from 246 (95% CI 224–270) to 165 (95% CI 149–182) per 100,000 people. However, incidence remained unaltered among those <65 years. Early case-fatality decreased from 14 to 11% (p = 0.165). ­Conclusion: First-ever stroke incidence in southern Sweden has decreased with 33% since the beginning of this millenni­um. Incidence rates have decreased among the elderly but remain unchanged among younger age groups. Our findings warrant further studies on trends in risk factor profiles and effects of prevention strategies, and heightened focus on stroke in the young.
Transient Receptor Potential Channel, Vanilloid 5, Induces Chondrocyte Apoptosis in a Rat Osteoarthritis Model Through the Mediation of Ca2+ Influx
Authors: Wei Yingliang , Zheng Dianbin , Guo Xiaocheng , Zhao Min , Gao Linlin , Bai Lunhao
Published: April 2018

Background/Aims: Chondrocyte apoptosis is the most common pathological feature in cartilage in osteoarthritis (OA). Transient receptor potential channel vanilloid 5 (TRPV5) is important in regulating calcium ion (Ca2+) influx. Accumulating evidences suggest that Ca2+ is a major intracellular second messenger that can trigger cell apoptosis. Therefore, we investigate the potential role of TRPV5 in mediating Ca2+ influx to promote chondrocyte apoptosis in OA. Methods: The monoiodoacetic acid (MIA)-induced rat OA model was assessed by macroscopic and radiographic analyses. Calmodulin protein immunolocalization was detected by immunohistochemistry. The mRNA and protein level of TRPV5, calmodulin and cleaved caspase-8 in articular cartilage were assessed by real time polymerase chain reaction and western blotting. Primary chondrocytes were isolated and cultured in vitro. TRPV5 small interfering RNA was used to silence TRPV5 in chondrocytes. Then, calmodulin and cleaved caspase-8 were immunolocalized by immunofluorescence in chondrocyte. Fluo-4AM staining was used to assess intracellular Ca2+ to reflect TRPV5 function of mediation Ca2+ influx. Annexin V-fluorescein isothiocyanatepropidium iodide flow cytometric analysis was performed to determine chondrocytes apoptosis. Western blotting techniques were used to measure the apoptosis-related proteins in chondrocyte level. Results: Here, we reported TRPV5 was up-regulated in MIA-induced OA articular cartilage. Ruthenium red (a TRPV5 inhibitor) can relieve progression of joint destruction in vivo which promoted us to demonstrate the effect of TRPV5 in OA. We found that TRPV5 had a specific role in mediating extracellular Ca2+ influx leading to chondrocytes apoptosis in vitro. The apoptotic effect was inhibited even reversed by silencing TRPV5. Furthermore, we found that the increase Ca2+ influx triggered apoptosis by up-regulating the protein of death-associated protein, FAS-associated death domain, cleaved caspase-8, cleaved caspase-3, cleaved caspase-6, and cleaved caspase-7, and the up-regulated proteins were abolished by silencing TRPV5 or 1, 2-bis-(o-Aminophenoxy)-ethane-N,N,N’,N’-tetraacetic acid, tetraacetoxymethyl ester (a Ca2+ chelating agent). Conclusion: The up-regulated TRPV5 could used be as an initiating factor that induces extrinsic chondrocyte apoptosis via the mediation of Ca2+ influx. These findings suggested TRPV5 could be an intriguing mediator for drug target in OA.
Necroptosis Contributes to Urban Particulate Matter-Induced Airway Epithelial Injury
Authors: Xu Feng , Luo Man , He Lulu , Cao Yuan , Li Wen , Ying Songmin , Chen Zhihua , Shen Huahao
Published: April 2018

Background/Aims: Necroptosis, a form of programmed necrosis, is involved in the pathologic process of several kinds of pulmonary diseases. However, the role of necroptosis in particulate matter (PM)–induced pulmonary injury remains unclear. The objective of this study is to investigate the involvement of necroptosis in the pathogenesis of PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction, both in vitro and in vivo. Methods: PM was administered into human bronchial epithelial (HBE) cells or mouse airways, and the inflammatory response and mucus production were assessed. The mRNA expressions of IL6, IL8 and MUC5AC in HBE cells and Cxcl1, Cxcl2, and Gm-csf in the lung tissues were detected by quantitative real-time RT-PCR. The secreted protein levels of IL6 and IL8 in culture supernatants and Cxcl1, Cxcl2, and Gm-csf in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). We used Western blot to measure the protein expressions of necroptosis-related proteins (RIPK1, RIPK3, and Phospho-MLKL), NF-κB (P65 and PP65), AP-1 (P-c-Jun and P-c-Fos) and MUC5AC. Cell necrosis and mitochondrial ROS were detected using flow cytometry. In addition, pathological changes and scoring of lung tissue samples were monitored using hemoxylin and eosin (H&E), periodic acid-schiff (PAS) and immunohistochemistry staining. Results: Our study showed that PM exposure induced RIP and MLKL-dependent necroptosis in HBE cells and in mouse lungs. Managing the necroptosis inhibitor Necrostatin-1 (Nec-1) and GSK’872, specific molecule inhibitors of necroptosis, markedly reduced PM-induced inflammatory cytokines, e.g., IL6 and IL8, and MUC5AC in HBE cells. Similarly, administering Nec-1 significantly reduced airway inflammation and mucus hyperproduction in PM-exposed mice. Mechanistically, we found PM–induced necroptosis was mediated by mitochondrial reactive oxygen species-dependent early growth response gene 1, which ultimately promoted inflammation and mucin expression through nuclear factor κB and activator protein-1 pathways, respectively. Conclusions: Our results demonstrate that necroptosis is involved in the pathogenesis of PM–induced pulmonary inflammation and mucus hyperproduction, and suggests that it may be a novel target for treatment of airway disorders or disease exacerbations with airborne particulate pollution.
Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal
Authors: Weigand Tim , Singler Benjamin , Fleming Thomas , Nawroth Peter , Klika Karel D. , Thiel Christian , Baelde Hans , Garbade Sven F. , Wagner Andreas H. , Hecker Markus , Yard Benito A. , Amberger Albert , Zschocke Johannes , Schmitt Claus P. , Peters Verena
Published: April 2018

Background/Aims: Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo. Methods: MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC. Results: In vitro, carnosine and anserine dose-dependently reduced N-carboxyethyl lysine (CEL) and advanced glycation end products (AGEs) formation. NMR studies revealed the formation of oligo/polymeric products of MG catalyzed by carnosine or anserine. MG toxicity (0.3-1 mM) was dose-dependent for podocytes, tubular and mesangial cells whereas low MG levels (0.2 mM) resulted in increased cell viability in podocytes (143±13%, p<0.001) and tubular cells (129±3%, p<0.001). Incubation with carnosine/anserine did not reduce MG-induced toxicity, independent of incubation times and across large ranges of MG to carnosine/anserine ratios. Cellular carnosine uptake was low (<0.1% in 20 hours) and cellular carnosine concentrations remained unaffected. The putative carnosine transporter PHT1 along with the taurine transporter (TauT) was expressed in all cell types while PEPT1, PEPT2 and PHT2, also belonging to the proton-coupled oligopeptide transporter (POT) family, were only expressed in tubular cells. Conclusion: While carnosine and anserine catalyze the formation of MG oligo/polymers, the molar ratios required for protection from MG-induced cellular toxicity are not achievable in renal cells. The effect of carnosine in vivo, to mitigate diabetic nephropathy may therefore be independent upon its ability to scavenge MG and/or carnosine is mainly acting extracellularly.
The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension
Authors: Polak Agnieszka , Harasim-Symbor Ewa , Malinowska Barbara , Kasacka Irena , Lewandowska Alicja , Chabowski Adrian
Published: April 2018

Background/Aims: Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension. Methods: Hypertension was induced by DOCA (25mg/kg) injections and addition of 1% NaCl in the drinking water for six weeks. Chronic activation of the ECS was performed by URB597 (1mg/kg) injections for two weeks. We examined fasting plasma levels of insulin (ELISA), glucose and intramyocardial glycogen (colorimetric method). Expressions of glucose transporters (GLUT1, 4) and selected proteins engaged in GLUT translocation as well as glucose metabolism were determined using Western blotting. Results: Hypertension induced hypoinsulinemia with concomitant lack of significant changes in glycemia, reduced intramyocardial glycogen content and increased pyruvate dehydrogenase (PDH) expression in the cardiac muscle. Importantly, chronic URB597 administration in the hypertensive rats increased insulin concentration, elevated plasmalemmal GLUT1 and GLUT4 expression and concomitantly improved myocardial glycogen storage. Conclusion: Chronic administration of fatty acid amide hydrolase (FAAH) inhibitor has potential protective properties on myocardial glucose metabolism in hypertension.
Crocin Improves the Endothelial Function Regulated by Kca3.1 Through ERK and Akt Signaling Pathways
Authors: Yang Huike , Li Xuemei , Liu Yang , Li Xinlei , Li Xiaodong , Wu Mengnan , Lv Xiaohong , Chunhua Chun , Ding Xuansheng , Zhang Yafang
Published: April 2018

Background/Aims: Based on the protective effect of crocin against cardiovascular diseases, we hypothesize that crocin could improve endothelial function through activating the eNOS(endothelial nitric oxide synthase) /NO pathway and/or the intermediate-conductance Ca2+-activated K+ channels (KCa3.1). Methods: In this study, rat aortic rings were used to assess the regulatory effect of crocin on vascular tone and nitric oxide, prostacyclin, and KCa3.1, all endothelial vasodilators, were analyzed for effects by crocin. The expression profiles of p-eNOS, total-eNOS, p-ERK, total-ERK, p-Akt, total-Akt, KCa3.1, CD31, thrombomodulin, ICAM-1 and VCAM-1 were tested by western blotting. KCa3.1 was also analyzed by qPCR and immunofluorescence staining. Fluorescence and confocal microscopy were used to determine NO generation and intracellular Ca2+. Both EdU and MTT assays were used to evaluate cell viability. Cellular migration was assessed using transwell assay. Results: Crocin relaxed pre-contracted artery rings through either NO or KCa3.1, but not PGI, in an endothelium-dependent manner. Furthermore, crocin increased p-eNOS, total-eNOS expression and NO production as well as intracellular Ca2+ in both HUVECs and HUAECs (Human Umbilical Artery Endothelial cells). Crocin also stimulated the expression of CD31, thrombomodulin and vascular cell adhesion molecule 1 (VCAM-1), as well as increased cellular proliferation and migration in vitro. Interestingly, we determined for the first time that by blocking or silencing KCa3.1 there was inhibition of crocin induced upregulation of p-eNOS and total-eNOS. Correspondingly, the KCa3.1 inhibitor TRAM-34 also reduced the expression of CD31, thrombomodulin and VCAM-1, as well as diminished intracellular Ca2+, cellular proliferation and migration. Finally, crocin stimulated the expression of p-ERK, total-ERK, p-Akt and total-Akt, however suppression of MEK and Akt inhibited this expression profile in endothelial cells. Conclusion: In the present study, these data strongly support the hypothesis that crocin could improve endothelial function through stimulation of the eNOS/NO pathway and other endothelial markers. This functional improvement is regulated by KCa3.1 via the MEK/ERK and PI3K/Akt signaling pathway.
Prevalence and Genotype Distribution of Hepatitis C Virus Infection among Patients with Type 2 Diabetes Mellitus
Authors: Farshadpour Fatemeh , Taherkhani Reza , Ravanbod Mohammad Reza , Eghbali Seyed Sajjad
Published: April 2018

Objective: This study was conducted to determine the prevalence and genotype distribution of hepatitis C virus (HCV) infection among patients with type 2 diabetes mellitus (DM). Subjects and Methods: We included 556 consecutive patients with confirmed type 2 DM attending the Diabetic Clinic of the Bushehr University of Medical Sciences and 733 nondiabetic subjects as controls. Serum levels of fasting blood sugar (FBS), alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH), and triglycerides (TG) were measured by enzymatic colorimetric methods, and the presence of anti-HCV antibodies was determined by enzyme-linked immunosorbent assay. Semi-nested reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequencing was performed on all anti-HCV-seropositive samples. Data were analyzed using the Statistical Package for the Social Sciences 17, and descriptive statistics, χ2 test, Fisher exact test, and the Student t test were used for analysis. Results: The seroprevalence of HCV in the diabetic patients was 1.98% (11/556), which was higher than HCV prevalence among the nondiabetic controls (4/733, 0.54%) (p = 0.032). No significant differences in ALT, AST, FBS, TG, and TCH levels were found between the HCV-seropositive and HCV-seronegative diabetic patients, although HCV-seropositive diabetic patients tended to have higher ALT, AST, and TCH levels, but lower TG and FBS levels than HCV-seronegative patients. In logistic regression analysis, only AST levels were significantly associated with HCV seropositivity among diabetic patients. The AST level of 41–80 IU/L was the only significant predictive variable for HCV seropositivity in the diabetic patients (odds ratio, 4.89; 95% CI: 1.06–22.49; p = 0.041). Of the 11 HCV-seropositive diabetic patients, 10 (91%) had HCV viremia with genotype 3a. Conclusion: Patients with type 2 DM had a higher prevalence of HCV infection than controls, and HCV seropositivity was independent of biochemical parameters.
Sanitation of House and School, Personal Hygiene and Infection of Soil Transmitted Helminths among Elementary School Students
Authors: Merisa Damanik Dina , Soeyoko Soeyoko , Sutomo Adi Heru
Published: April 2018

In Indonesia, soil transmitted helminths (STH) infection is still a public health problem particularly in the child of elementary school age. The high of that infection was also supported by low environmental sanitation and poor personal hygiene. STH infection is one of 10 great of frequent diseases in Palue Island and in this region still able can be found an adult worm in feces even from regurgitate. This was observational analytic study by cross sectional design. The location of the study was Palue Island, Sikka Regency, East Nusa Tenggara. The repondents of the study was 100 students of eight elementary school. Diagnosis of STH infection was establised based on worm eggs examination in feces used floatation method. Questionnaire, and check list were the instruments for collecting data in this study. There were significant relationship between house’s environmental sanitation (p=0.043), school’s environmental sanitation (p= 0.000), personal hygiene (p = 0.032) with STH infection among the students of elementary school in Palue Island, Sikka Regency, East Nusa Tenggara. Multivariate analysis obtained that personal hygiene was the most influence variable to the STH infection in this region.
Prooxidative Role of Hyperinsulinemia in Metabolic Sydrome Formation
Authors: Uzbekova Nelli , Musakhodjaeva Dilorom Abdullaevna
Published: April 2018

The pattern of hyperinsulinemia was studied in patients with metabolic syndrome. The levels of basal insulinemia (BI), malondialdehyde (MDA) and catalaze (CA) as an index of oxidative stress and some metabolic parameters have been studied in men and women with metabolic syndrome. Basal insulinemia correlated significantly with malondialdehyde levels both in men and women. Close relationship was also found between basal insulinemia and waist circumference.
The Determinants and Subsequent Effect of Self-Rated Health Status on Survival among Elderly Americans
Authors: Han Guangming
Published: April 2018

The main aim of this study is to explore the patterns, determinants and subsequent mortality prediction of change in self-rated health in the elderly American population. To achieve this purpose, we constructed logistic regression models and Cox proportional hazard regression models with the complex survey dataset from the National Second Longitudinal Study of Aging (LSOA II) to calculate the odds ratios (OR)/ hazard ratios (HR) and confidence intervals (CI) of risk factors. Our results show that chronic disease condition and difficulty in daily activities are the main reasons for change in self-rated health status. Furthermore, change in self-rated health has significant impact on survival function in the elderly populations. When change in self-rated health status was considered, self-rated health was a stronger and more flexible predictor of mortality for elderly populations. These findings will provide important information to establish effective strategies for prolonging lifespan by improving self-rated health status for elderly populations.