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Find video protocols related to scientific articles indexed in Pubmed.
DATA SYNTHESIS AND METHOD EVALUATION FOR BRAIN IMAGING GENETICS.
Proc IEEE Int Symp Biomed Imaging
PUBLISHED: 11-20-2014
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Brain imaging genetics is an emergent research field where the association between genetic variations such as single nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is evaluated. Sparse canonical correlation analysis (SCCA) is a bi-multivariate analysis method that has the potential to reveal complex multi-SNP-multi-QT associations. We present initial efforts on evaluating a few SCCA methods for brain imaging genetics. This includes a data synthesis method to create realistic imaging genetics data with known SNP-QT associations, application of three SCCA algorithms to the synthetic data, and comparative study of their performances. Our empirical results suggest, approximating covariance structure using an identity or diagonal matrix, an approach used in these SCCA algorithms, could limit the SCCA capability in identifying the underlying imaging genetics associations. An interesting future direction is to develop enhanced SCCA methods that effectively take into account the covariance structures in the imaging genetics data.
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Supramolecular polymeric vesicles formed by p-sulfonatocalix[4]arene and chitosan with multistimuli responses.
Soft Matter
PUBLISHED: 11-20-2014
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Supramolecular polymeric vesicles are constructed by the complexation of p-sulfonatocalix[4]arene and chitosan, where the multivalent electrostatic interactions between the anionic sulfonate tetramer and cationic polyammoniums served as the dominant driving force. The supra-amphiphilic assemblies are disassembled upon exposure to a pH stimulus since the partial deprotonation of chitosan accompanied by a pH increase. Adding a competitive guest can also disrupt the assembly, representing the host-guest inclusion response. Interestingly, an abnormal temperature-response is observed, possibly as a result of the temperature-directed fusion process.
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Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents.
ACS Med Chem Lett
PUBLISHED: 11-13-2014
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New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 ?M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 ?M·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
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Simulation of Late Inspiratory Rise in Airway Pressure During Pressure Support Ventilation.
Respir Care
PUBLISHED: 11-06-2014
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Late inspiratory rise in airway pressure (LIRAP, Paw/?T) caused by inspiratory muscle relaxation or expiratory muscle contraction is frequently seen during pressure support ventilation (PSV), although the modulating factors are unknown.
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Automated Dispersive Solid-Phase Extraction Using Dissolvable Fe3O4-Layered Double Hydroxide Core-Shell Microspheres as Sorbent.
Anal. Chem.
PUBLISHED: 10-30-2014
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Automation of dispersive solid-phase extraction (d-SPE) presents significant challenges. Separation of the sorbent from the spent sample cannot be conducted without manual operations, including centrifugation, a widely used means of isolating a solid material from solution. In this work, we report an approach to d-SPE using dissolvable magnetic Fe3O4-layered double hydroxide core-shell microspheres as sorbent to enable automation of the integrative extraction and analytical processes. Through magnetic force, the sorbent, after extraction, was isolated from the sample and then dissolved by acid to release the analytes. Thus the customary analyte elution step in conventional SPE was unnecessary. The automated d-SPE step was coupled to high-performance liquid chromatography (HPLC) with photodiode array detection for determination of several pharmaceuticals and personal care products (PPCPs) [acetylsalicylic acid (ASA), 2,5-dihydroxybenzoic acid (DBA), 2-phenylphenol (PP), and fenoprofen (FP)] in aqueous samples. For the automated d-SPE process, experimental parameters such as agitation speed, temperature, time, and pH were optimized. The results showed that this method provided low limits of detection (between 0.021 and 0.042 ?g/L), good linearity (r(2) ? 0.9956), and good repeatability of extractions (relative standard deviations ?4.1%, n = 6). The optimized procedure was then applied to determination of PPCPs in a sewage sample and ASA and FP in drug preparations. This fully automated extraction-HPLC approach was demonstrated to be an efficient procedure for extraction and analysis of ASA, DBA, PP, and FP in these samples.
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The application of flow cytometry for evaluating biological aggressiveness of intracranial meningiomas.
Cytometry B Clin Cytom
PUBLISHED: 09-23-2014
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Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas.
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Mechanisms of nanosized titanium dioxide-induced testicular oxidative stress and apoptosis in male mice.
Part Fibre Toxicol
PUBLISHED: 09-12-2014
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BackgroundDue to the increased application of titanium dioxide nanoparticles (TiO2 NPs) in the food industry and daily life, their potential toxic effects in humans and animals have been investigated. However, very few studies have focused on testicular oxidative stress and/or apoptosis.MethodsIn order to understand the possible molecular mechanisms of testicular lesions following exposure to TiO2 NPs, male mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days. Testicular oxidative stress and apoptosis were then evaluated, and the testicular mRNA expression of several genes and their proteins involved in oxidative stress and/or apoptosis was investigated.ResultsTiO2 NPs entered Sertoli cells and caused severe testicular oxidative damage and/or apoptosis, accompanied by excessive production of reactive oxygen species and peroxidation of lipids, proteins and DNA as well as a significant reduction in antioxidant capacity. Furthermore, exposure to TiO2 NPs resulted in the up-regulation of caspase-3, Nrbp2, and cytochrome c expression, and caused down-regulation of SOD, CAT, GPx, GST, GR, Cyp1b1, Car3, Bcl-2, Acaa2, and Axud1 expression in mouse testis.ConclusionsTiO2 NPs entered Sertoli cells via the blood-testis barrier and were deposited in mouse seminiferous cord and/or Sertoli cells, causing oxidative damage and apoptosis.
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Prevalence, incidence, and comorbidity of clinically diagnosed obsessive-compulsive disorder in Taiwan: A national population-based study.
Psychiatry Res
PUBLISHED: 08-15-2014
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Obsessive-compulsive disorder (OCD) is a chronic debilitating anxiety disorder significant in intrusive thoughts and compensation repetitive behaviors. Few studies have reported on this condition Asia. This study estimated the prevalence, incidence and psychiatric comorbidities of OCD in Taiwan. We identified study subjects for 2000-2008 with a principal diagnosis of OCD according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic criteria by using National Health Research Institute database. These patients received either outpatient or inpatient care for their condition. Rates were directly age- and sex-adjusted to the 2004 Taiwan population distribution. The estimated mean annual incidence was 27.57 per 10(5) inhabitants and the one year prevalence was 65.05 per 10(5) inhabitants. Incidence and prevalence increased with age, peaking at age 18-24 years in males and at 35-44 years in females. About 53% of adults (?18 years) and 48% of child and adolescent patients (6-17 years) had one or more comorbid psychiatric conditions. The most common comorbid diagnosis was depressive disorders for both adult and child-adolescent patients. We found a lower prevalence and incidence of clinically diagnosed OCD than that of community studies. Many Asian patients with OCD also had various psychiatric comorbidities, a clinically relevant finding.
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Comparison of skin and soft tissue infections caused by Vibrio and Aeromonas species.
Surg Infect (Larchmt)
PUBLISHED: 08-15-2014
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Abstract Background: The aim of this study was to compare skin and soft tissue infections (SSTIs) caused by Vibrio and Aeromonas spp.
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The Combination Use of Platelet-Rich Fibrin and Treated Dentin Matrix for Tooth Root Regeneration by Cell Homing.
Tissue Eng Part A
PUBLISHED: 08-11-2014
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Endogenous regeneration through cell homing provides an alternative approach for tissue regeneration, except cell transplantation, especially considering clinical translation. However, tooth root regeneration through cell homing remains a provocative approach in need of intensive study. Both platelet-rich fibrin (PRF) and treated dentin matrix (TDM) are warehouses of various growth factors, which can promote cell homing. We hypothesized that endogenous stem cells are able to sense biological cues from PRF membrane and TDM, and contribute to the regeneration of tooth root, including soft and hard periodontal tissues. Therefore, the biological effects of canine PRF and TDM on periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMSCs) were evaluated respectively in vitro. Beagle dogs were used as orthotopic transplantation model. It was found that PRF significantly recruited and stimulated the proliferation of PDLSCs and BMSCs in vitro. Together, PRF and TDM induced cell differentiation by upregulating the mineralization-related gene expression of bone sialoprotein (BSP) and osteopotin (OPN) after 7 days coculture. In vivo, transplantation of autologous PRF and allogeneic TDM into fresh tooth extraction socket achieved successful root regeneration 3 months postsurgery, characterized by the regeneration of cementum and periodontal ligament (PDL)-like tissues with orientated fibers, indicative of functional restoration. The results suggest that tooth root connected to the alveolar bone by cementum-PDL complex can be regenerated through the implantation of PRF and TDM in a tooth socket microenvironment, probably by homing of BMSCs and PDLSCs. Furthermore, bioactive cues and inductive microenvironment are key factors for endogenous regeneration. This approach provides a tangible pathway toward clinical translation.
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Synthetically chemical-electrical mechanism for controlling large scale reversible deformation of liquid metal objects.
Sci Rep
PUBLISHED: 08-08-2014
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Reversible deformation of a machine holds enormous promise across many scientific areas ranging from mechanical engineering to applied physics. So far, such capabilities are still hard to achieve through conventional rigid materials or depending mainly on elastomeric materials, which however own rather limited performances and require complicated manipulations. Here, we show a basic strategy which is fundamentally different from the existing ones to realize large scale reversible deformation through controlling the working materials via the synthetically chemical-electrical mechanism (SCHEME). Such activity incorporates an object of liquid metal gallium whose surface area could spread up to five times of its original size and vice versa under low energy consumption. Particularly, the alterable surface tension based on combination of chemical dissolution and electrochemical oxidation is ascribed to the reversible shape transformation, which works much more flexible than many former deformation principles through converting electrical energy into mechanical movement. A series of very unusual phenomena regarding the reversible configurational shifts are disclosed with dominant factors clarified. This study opens a generalized way to combine the liquid metal serving as shape-variable element with the SCHEME to compose functional soft machines, which implies huge potential for developing future smart robots to fulfill various complicated tasks.
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Sleep Apnea and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.
Sleep
PUBLISHED: 08-06-2014
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Sleep apnea (SA) is characterized by apnea during sleep and is associated with cardiovascular diseases and an increase in all-cause mortality. Chronic kidney disease (CKD) is a global health problem that has placed a substantial burden on healthcare resources. However, the relationship between SA and the incidence of CKD is not clear. This study aimed to determine whether SA is an independent risk factor for the development of CKD.
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An improved sensor for precision detection of in situ stem water content using a frequency domain fringing capacitor.
New Phytol.
PUBLISHED: 07-28-2014
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One role of stems is that of water storage. The water content of stems increases and decreases as xylem water potential increases and decreases, respectively. Hence, a nondestructive method to measure stem water content (StWC) = (volume of water) : (volume of stem), could be useful in monitoring the drought stress status of plants. We introduce a frequency domain inner fringing capacitor-sensor for measuring StWC which operates at 100 MHz frequency. The capacitor-sensor consists of two wave guides (5-mm-wide braided metal) that snugly fit around the surface of a stem with a spacing of 4-5 mm between guides. Laboratory measurements on analog stems reveals that the DC signal output responds linearly to the relative dielectric constant of the analog stem, is most sensitive to water content between the waveguides to a depth of c. 3 mm from the stem surface, and calibrations based on the gravimetric water loss of excised stems of plants revealed a resolution in StWC of < ± 0.001 v/ v. The sensor performed very well on whole plants with a 100-fold increased resolution compared with previous frequency domain and time domain reflectometry methods and, hence, may be very useful for future research requiring nondestructive measurements of whole plants.
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Nanoparticle-based monoliths for chromatographic separations.
Analyst
PUBLISHED: 07-10-2014
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As an intriguing member of the monolith family, nanoparticle-based monoliths have recently emerged as a new class of promising substrates in analytical sample preparation and separation science because of their many distinct characteristics such as high permeability and readily available tailored surface chemistries. This mini-review article specifically summarizes and highlights the latest major advances in the application of nanoparticle-based monoliths for chromatographic separations during the past three years.
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Th2 factors may be involved in TiO? NP-induced hepatic inflammation.
J. Agric. Food Chem.
PUBLISHED: 07-08-2014
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TiO2 nanoparticles (NPs) are used in the food industry but have potential toxic effects in humans and animals. The resulting immune response is driven by the production of Th2 cytokines IL-4 and IL-5, which contribute to the development of hepatic inflammation. However, TiO2 NPs have been demonstrated to impair liver function and cause liver inflammation in animal models, which may be associated with activation of Th2 factor-mediated pathways. Mice were administered a gavage instillation of 2.5, 5, or 10 mg/kg body weight TiO2 NPs for six consecutive months. We investigated whether TiO2 NPs activate the Th2 factor-mediated signaling pathway under TiO2 NP-induced hepatic toxicity. The results showed that mice exhibited an accumulation of titanium in the liver, which in turn led to reductions in body weight, increases in liver indices, liver dysfunction, infiltration of inflammatory cells, and hepatocyte apoptosis or necrosis. Furthermore, hepatic inflammation was accompanied by increased (0.67 ± 0.09- to 2.14 ± 0.19-fold) IL-4 expression and up-regulation of its target genes including IL-5 (0.1 ± 0.06- to 0.69 ± 0.12-fold), IL-12 (0.08 ± 0.03- to 0.83 ± 0.21-fold), IFN-? (0.17 ± 0.09- to 0.87 ± 0.15-fold), GATA3 (0.05 ± 0.02- to 1.29 ± 0.18-fold), GATA4 (0.04 ± 0.01- to 0.87 ± 0.13-fold), T-bet (0.3 ± 0.06- to 0.93 ± 0.15-fold), ROR?t (0.32 ± 0.11- to 1.67 ± 0.17-fold), STAt3 (0.16 ± 0.06- to 2.14 ± 0.23-fold), STAT6 (0.2 ± 0.05- to 0.63 ± 0.12-fold), eotaxin (0.53 ± 0.13- to 1.49 ± 0.21-fold), MCP-1 (0.5 ± 0.11- to 0.74 ± 0.18-fold), and MIP-2 (0.27 ± 0.07- to 0.71 ± 0.18-fold) and significant down-regulation of its target gene STAT1 (-0.15 ± 0.05 to -0.81 ± 0.11-fold). Taken together, the alteration of Th2 factor expression may be involved in the control of hepatic inflammation induced by chronic TiO2 NP toxicity.
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PIGD: a database for intronless genes in the Poaceae.
BMC Genomics
PUBLISHED: 06-30-2014
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Intronless genes are a feature of prokaryotes; however, they are widespread and unequally distributed among eukaryotes and represent an important resource to study the evolution of gene architecture. Although many databases on exons and introns exist, there is currently no cohesive database that collects intronless genes in plants into a single database.
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Mechanism of TiO2 nanoparticle-induced neurotoxicity in zebrafish (Danio rerio).
Environ. Toxicol.
PUBLISHED: 06-07-2014
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Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO2 NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior-related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 ?g/L TiO2 NPs for 45 consecutive days. Our data indicated that spatial recognition memory and levels of norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased and NO levels were markedly elevated, and over proliferation of glial cells, neuron apoptosis, and TiO2 NP aggregation were observed after low dose exposures of TiO2 NPs. Furthermore, the low dose exposures of TiO2 NPs significantly activated expressions of C-fos, C-jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab, and GluR2 genes. These findings imply that low dose exposures of TiO2 NPs may result in the brain damages in zebrafish, provide a developmental basis for evaluating the neurotoxicity of subchronic exposure, and raise the caution of aquatic application of TiO2 NPs. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.
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Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population.
Respirology
PUBLISHED: 06-02-2014
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Although surfactant protein-D (SP-D) has been suggested as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship between genetic variants of SP-D and disease outcome of COPD remains unknown. We hypothesized that genetic polymorphisms of SP-D are associated with COPD-related phenotypes and disease prognosis.
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Mechanisms of TiO2 nanoparticle-induced neuronal apoptosis in rat primary cultured hippocampal neurons.
J Biomed Mater Res A
PUBLISHED: 06-01-2014
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Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to decrease learning and memory of animals. However, whether the impacts of these NPs on the recognition function are involved in hippocamal neuron damages is poorly understood. In this study, primary cultured hippocampal neurons from one-day-old fetal Sprague-Dawley rats were exposed to 5, 15, or 30 ?g/mL TiO2 NPs for 24 h, we investigated cell viability, ultrastructure, and mitochondrial membrane potential (MMP), calcium homeostasis, oxidative stress, antioxidant capacity, apoptotic signaling pathway associated with the primary cultured hippocamal neuron apoptosis. Our findings showed that TiO2 NP treatment resulted in reduction of cell viability, promoted lactate dehydrogenase release, apoptosis and increased neuron apoptotic rate in a dose-dependent manner. Furthermore, TiO2 NPs led to [Ca(2+) ]i elevation, and mitochondrial membrane potential reduction, up-regulated protein expression of cytochrome c, Bax, caspase-3, glucose-regulate protein 78, C/EBP homologous protein and caspase-12, and down-regulated bcl-2 expression in the primary cultured hippocampal neurons. These findings suggested that hippocampal neuron apoptosis caused by TiO2 NPs may be associated with mitochondria-mediated signal pathway and endoplasmic reticulum-mediated signal pathway.
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Nano-sized titanium dioxide-induced splenic toxicity: a biological pathway explored using microarray technology.
J. Hazard. Mater.
PUBLISHED: 06-01-2014
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Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various areas, and its potential toxicity has gained wide attention. However, the molecular mechanisms of multiple genes working together in the TiO2 NP-induced splenic injury are not well understood. In the present study, 2.5, 5, or 10mg/kg body weight TiO2 NPs were administered to the mice by intragastric administration for 90 consecutive days, their immune capacity in the spleen as well as the gene-expressed characteristics in the mouse damaged spleen were investigated using microarray assay. The findings showed that with increased dose, TiO2 NP exposure resulted in the increases of spleen indices, immune dysfunction, and severe macrophage infiltration as well as apoptosis in the spleen. Importantly, microarray data showed significant alterations in the expressions of 1041 genes involved in immune/inflammatory responses, apoptosis, oxidative stress, stress responses, metabolic processes, ion transport, signal transduction, cell proliferation/division, cytoskeleton and translation in the 10 mg/kg TiO2 NP-exposed spleen. Specifically, Cyp2e1, Sod3, Mt1, Mt2, Atf4, Chac1, H2-k1, Cxcl13, Ccl24, Cd14, Lbp, Cd80, Cd86, Cd28, Il7r, Il12a, Cfd, and Fcnb may be potential biomarkers of spleen toxicity following exposure to TiO2 NPs.
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Increased risk of hip fractures in patients with dementia: a nationwide population-based study.
BMC Neurol
PUBLISHED: 05-26-2014
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BackgroundDementia has been associated with an increased risk of hip fracture. However, little research has been conducted on the impact of dementia on wrist or vertebral fracture development. The aim of this study was to investigate whether dementia is a risk factor for different types of fracture in Taiwan.MethodsThe study sample was drawn from Taiwan¿s National Health Insurance Research Database of reimbursement claims, and comprised 1408 patients who visited ambulatory care centers or were hospitalized with a diagnosis of dementia. The comparison group consisted of 7040 randomly selected individuals. Cox proportional hazard regression model was used to examine associations between dementia and the risk of different types of fracture.ResultsDuring a 3-year follow-up period, 264 patients with dementia (18.75%) and 1098 patients without dementia (15.60%) developed fractures. Dementia was independently associated with increased risk of hip fracture [adjusted hazard ratio (HR) 1.92, 95% CI 1.48¿2.49]. Patients with dementia and osteoporosis had the highest risk of developing hip fracture (adjusted HR 2.27, 95% CI 1.28¿4.01). Dementia did not increase wrist fracture or vertebral fracture risk when compared to the control group, even in patients with osteoporosis.ConclusionsIndividuals with dementia are at greater risk of developing hip fracture, particularly if they also have osteoporosis. Early mental screening programs and health education should be initiated to decrease disability and dependence in patients with dementia.
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Prognostic factors and treatment outcomes for patients with surgically staged uterine clear cell carcinoma focusing on the early stage: A Taiwanese Gynecologic Oncology Group study.
Gynecol. Oncol.
PUBLISHED: 05-14-2014
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The aim of this study was to investigate the clinical and pathological characteristics of uterine clear cell carcinoma (UCCC) and the treatment of this disease in relation to patient outcomes.
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A novel Maize homeodomain-leucine zipper (HD-Zip) I gene, Zmhdz10, positively regulates drought and salt tolerance in both rice and Arabidopsis.
Plant Cell Physiol.
PUBLISHED: 05-08-2014
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Increasing evidence suggests that homeodomain-leucine zipper I (HD-Zip) I transcription factors play important roles in abiotic stress responses, but no HD-Zip I proteins have been reported in maize. Here, a drought-induced HD-Zip I gene, Zmhdz10, was isolated from maize and characterized for its role in stress responses. Real-time quantitative PCR showed that expression of Zmhdz10 was also induced by salt stress and ABA. Transient expression of Zmhdz10-green fluorescent protein (GFP) fusion proteins in onion cells showed a nuclear localization of Zmhdz10. Yeast hybrid assays demonstrated that Zmhdz10 has transactivation and DNA-binding activity in yeast cells. Overexpression of Zmhdz10 in rice led to enhanced tolerance to drought and salt stresses and increased sensitivity to ABA. Moreover, Zmhdz10 transgenic plants had lower relative electrolyte leakage (REL), lower malondialdehyde (MDA) and increased proline content relative to wild-type plants under stress conditions, which may contribute to enhanced stress tolerance. Zmhdz10 transgenic Arabidopsis plants also exhibited enhanced tolerance to drought and salt stresses that was concomitant with altered expression of stress/ABA-responsive genes, including ?1-Pyrroline-5-carboxylate synthetase 1 (P5CS1), Responsive to dehydration 22 (RD22), Responsive to dehydration 29B (RD29B) and ABA-insensitive 1 (ABI1). Taken together, these results suggest that Zmhdz10 functions as a transcriptional regulator that can positively regulate drought and salt tolerance in plants through an ABA-dependent signaling pathway.
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An increase in integrin-linked kinase non-canonically confers NF-¿B-mediated growth advantages to gastric cancer cells by activating ERK1/2.
Cell Commun. Signal
PUBLISHED: 05-07-2014
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BackgroundIncreased activity or expression of integrin-linked kinase (ILK), which regulates cell adhesion, migration, and proliferation, leads to oncogenesis. We identified the molecular basis for the regulation of ILK and its alternative role in conferring ERK1/2/NF-¿B-mediated growth advantages to gastric cancer cells.ResultsInhibiting ILK with short hairpin RNA or T315, a putative ILK inhibitor, abolished NF-¿B-mediated the growth in the human gastric cancer cells AGS, SNU-1, MKN45, and GES-1. ILK stimulated Ras activity to activate the c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of ¿B¿/NF-¿B signaling by facilitating the formation of the IQ motif-containing GTPase-activating protein 1 (IQGAP1)¿Ras complex. Forced enzymatic ILK expression promoted cell growth by facilitating ERK1/2/NF-¿B signaling. PI3K activation or decreased PTEN expression prolonged ERK1/2 activation by protecting ILK from proteasome-mediated degradation. C-terminus of heat shock cognate 70 interacting protein, an HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to control PI3K- and HSP90-regulated ILK stabilization and signaling. In addition to cell growth, the identified pathway promoted cell migration and reduced the sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and cisplatin. Additionally, exogenous administration of EGF as well as overexpression of EGFR triggered ILK- and IQGAP1-regulated ERK1/2/NF-¿B activation, cell growth, and migration.ConclusionAn increase in ILK non-canonically promotes ERK1/2/NF-¿B activation and leads to the growth of gastric cancer cells.
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Gene-gene interactions and risk of recurrent miscarriages in carriers of endocrine gland-derived vascular endothelial growth factor and prokineticin receptor polymorphisms.
Fertil. Steril.
PUBLISHED: 05-05-2014
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To study endocrine gland-derived vascular endothelial growth factor (EG-VEGF), prokineticin receptor (PROKR) 1, and PROKR2 variants in the coding regions of idiopathic recurrent miscarriage (RM) patients and further evaluate gene-gene interactions of these three genes.
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Push-fast recommendation on performing cardiopulmonary resuscitation causes excessive chest compression rates, a manikin model.
Am J Emerg Med
PUBLISHED: 05-03-2014
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Increasing chest compression rate during cardiopulmonary resuscitation can affect the workload and, ultimately, the quality of chest compression. This study examines the effects of compression at the rate of as-fast-as-you-can on cardiopulmonary resuscitation (CPR) performance.
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HO-1 attenuates hippocampal neurons injury via the activation of BDNF-TrkB-PI3K/Akt signaling pathway in stroke.
Brain Res.
PUBLISHED: 04-30-2014
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Although recent studies have found that HO-1 plays an important role in neuronal survival, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of HO-1 against ischemic brain injury induced by cerebral I/R and to explore whether the BDNF-TrkB-PI3K/Akt signaling pathway contributed to the protection provided by HO-1. Over-expressed HO-1 plasmids were employed to induce the overexpression of HO-1 through hippocampi CA1 injection 5 days before the cerebral I/R animal model was induced by four-vessel occlusion for 15 min transient ischemia and followed by reperfusion in Sprague-Dawley rats. Immunoblotting was carried out to examine the expression of the related proteins, and HE-staining was used to detect the percentage of living neurons in the hippocampal CA1 region. The results showed that over-expressed HO-1 could significantly protect neurons against cerebral I/R. Furthermore, the protein expression of BDNF, TrkB and p-Akt also increased in the rats treated with over-expressed HO-1 plasmids. However, treatment with tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) reversed the HO-1-induced increase in BDNF and p-Akt protein levels and decreased the level of cleaved caspase-3 protein in I/R rats. In summary, our results imply that HO-1 can decrease cell apoptosis in the I/R rat brain and that the mechanism may be related to the activation of the BDNF-TrkB-PI3K/Akt signaling pathway.
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Relationship between betel quid chewing and risks of cardiovascular disease in older adults: a cross-sectional study in Taiwan.
Drug Alcohol Depend
PUBLISHED: 04-28-2014
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The association between betel quid (BQ) chewing and oral cancer is well established. However, evidence regarding the relationship between BQ chewing and cardiovascular disease (CVD) is still insufficient.
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Novel N-substituted sophoridinol derivatives as anticancer agents.
Eur J Med Chem
PUBLISHED: 04-23-2014
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Using sophoridine (1) as the lead compound, a series of new N-substituted sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. SAR analysis indicated that introduction of a chlorobenzyl on the 12-nitrogen atom of sophoridinol might significantly enhance the antiproliferative activity. Of the newly synthesized compounds, sophoridinol analogue 9k exhibited a potent effect against six human tumor cell lines (liver, colon, breast, lung, glioma and nasopharyngeal). The mode of action of 9k was to inhibit the DNA topoisomerase I activity, followed by the G0/G1 phase arrest. It also showed a moderate oral bioavailability and good safety in vivo. Therefore, compound 9k has been selected as a novel-scaffold lead for further structural optimizations or as a chemical probe for exploring anticancer pathways of this kinds of compounds.
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Supramolecular chemistry of p-sulfonatocalix[n]arenes and its biological applications.
Acc. Chem. Res.
PUBLISHED: 03-25-2014
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CONSPECTUS: Developments in macrocyclic chemistry have led to supramolecular chemistry, a field that has attracted increasing attention among researchers in various disciplines. Notably, the discoveries of new types of macrocyclic hosts have served as important milestones in the field. Researchers have explored the supramolecular chemistry of several classical macrocyclic hosts, including crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Calixarenes represent a third generation of supramolecular hosts after cyclodextrins and crown ethers. Easily modified, these macrocycles show great potential as simple scaffolds to build podand-like receptors. However, the inclusion properties of the cavities of unmodified calixarenes are not as good as those of other common macrocycles. Calixarenes require extensive chemical modifications to achieve efficient endo-complexation. p-Sulfonatocalix[n]arenes (SCnAs, n = 4-8) are a family of water-soluble calixarene derivatives that in aqueous media bind to guest molecules in their cavities. Their cavities are three-dimensional and ?-electron-rich with multiple sulfonate groups, which endow them with fascinating affinities and selectivities, especially toward organic cations. They also can serve as scaffolds for functional, responsive host-guest systems. Moreover, SCnAs are biocompatible, which makes them potentially useful for diverse life sciences and pharmaceutical applications. In this Account, we summarize recent work on the recognition and assembly properties unique to SCnAs and their potential biological applications, by our group and by other laboratories. Initially examining simple host-guest systems, we describe the development of a series of functional host-guest pairs based on the molecular recognition between SCnAs and guest molecules. Such pairs can be used for fluorescent sensing systems, enzymatic activity assays, and pesticide detoxification. Although most macrocyclic hosts prevent self-aggregation of guest molecules, SCnAs can induce self-aggregation. Researchers have exploited calixarene-induced aggregation to construct supramolecular binary vesicles. These vesicles respond to internal and external stimuli, including temperature changes, redox reactions, additives, and enzymatic reactions. Such structures could be used as drug delivery vehicles. Although several biological applications of SCnAs have been reported, this field is still in its infancy. Continued exploration of the supramolecular chemistry of SCnAs will not only improve the existing biological functions but also open new avenues for the use of SCnAs in the fields of biology, biotechnology, and pharmaceutical research. In addition, we expect that other interdisciplinary research efforts will accelerate developments in the supramolecular chemistry of SCnAs.
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Supra-amphiphilic aggregates formed by p-sulfonatocalix[4]arenes and the antipsychotic drug chlorpromazine.
Soft Matter
PUBLISHED: 03-22-2014
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We report here a supramolecular strategy to directly assemble the small molecular antipsychotic drug chlorpromazine (CPZ) into nanostructures, induced by p-sulfonatocalix[4]arene (SC4A) and p-sulfonatocalix[4]arene tetraheptyl ether (SC4AH), with high drug loading efficiencies of 61% and 46%, respectively. The binary host-guest assembly process was monitored using optical transmittance measurements, and the size and morphology of these two kinds of supra-amphiphilic assemblies were identified using a combination of light scattering and high-resolution transmission electron microscopy, which showed solid spherical micelles. This strategy presents new opportunities for the development of high loading drug-containing carriers with easy processability for drug delivery.
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A Supramolecular Vesicle Based on the Complexation of p-Sulfonatocalixarene with Protamine and its Trypsin-Triggered Controllable-Release Properties.
Chemistry
PUBLISHED: 03-06-2014
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Enzyme-responsive assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites at which the target enzymes are located. In this work, based on the concept of host-guest chemistry, a trypsin-responsive supramolecular vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural serine protease trypsin-cleavable cationic protein protamine as the guest molecule, is reported. The complexation of p-sulfonatocalix[4]arene with protamine directs the formation of a supramolecular binary vesicle, which is dissipated by trypsin with high selectivity. Therefore, the present system represents a principle-of-concept to build a controlled-release carrier at trypsin-overexpressed sites.
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Analysis of bowel sounds application status for gastrointestinal function monitoring in the intensive care unit.
Crit Care Nurs Q
PUBLISHED: 03-06-2014
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The auscultation of bowel sounds (BS) has been neglected as a reliable tool for determining gastrointestinal (GI) functioning in the critically ill patient. This article considers the validity of BS auscultation in the assessment and management of critically ill patients and outlines how the information may be utilized for monitoring GI function. A descriptive, cross-sectional design with self-administered questionnaires was used to survey 132 nurses and 38 doctors in the 6 general intensive care units in Beijing hospitals. Descriptive statistics and chi-square test analyses were used to assess the level of knowledge about BS among Chinese doctors and nurses and to determine how they applied their BS auscultation findings in the care of critically ill patients. Bowel sounds were found to be the primary indicator for determining GI functioning in the unconscious, critically ill patient. However, only 11.4% of nurses and 47.6% of doctors could make correct clinical judgments on the basis of their auscultatory findings. The attitudes of nurses and doctors differed significantly on whether BS auscultation was needed to monitor GI function for unconscious patients. Bowel sounds auscultation remains an important indicator of GI function. Distinct and feasible standards regarding BS auscultation and results interpretation need to be established.
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Recent advances of ionic liquids and polymeric ionic liquids in capillary electrophoresis and capillary electrochromatography.
J Chromatogr A
PUBLISHED: 03-04-2014
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Ionic liquids (ILs) and polymeric ionic liquids (PILs) with unique and fascinating properties have drawn considerable interest for their use in separation science, especially in chromatographic techniques. In this article, significant contributions of ILs and PILs in the improvement of capillary electrophoresis and capillary electrochromatography are described, and a specific overview of the most relevant examples of their applications in the last five years is also given. Accordingly, some general conclusions and future perspectives in these areas are discussed.
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Synthesis of doubly ethyl-bridged bis(p-sulfonatocalix[4]arene) and its supramolecular polymerization with viologen dimer.
Chemistry
PUBLISHED: 02-26-2014
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A water-soluble supramolecular polymer with a high degree of polymerization and viscosity has been constructed based on the strong host-guest interaction between p-sulfonatocalix[4]arenes (SC4As) and viologen. A homoditopic doubly ethyl-bridged bis(p-sulfonatocalix[4]arene) (d-SC4A) was prepared and its binding behavior towards methyl viologen compared with the singly ethyl-bridged bis(p-sulfonatocalix[4]arene) (s-SC4A) by NMR spectroscopy and isothermal titration calorimetry. By employing a viologen dimer (bisMV(4+)) as the homoditopic guest, two linear AA/BB-type supramolecular polymers, d-SC4A?bisMV(4+) and s-SC4A?bisMV(4+), were successfully constructed. Compared with s-SC4A?bisMV(4+), d-SC4A?bisMV(4+) shows much higher solubility and viscosity, and has also been characterized by viscosity, diffusion-ordered NMR spectroscopy, dynamic light scattering, and atomic force microscopy measurements. Furthermore, the polymer is responsive to electrostimulus as viologen is electroactive, which was studied by cyclic voltammetry. This study represents a proof-of-principle as the polymer can potentially be applied as a self-healing and degradable polymeric material.
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Diverse transformations of liquid metals between different morphologies.
Adv. Mater. Weinheim
PUBLISHED: 02-22-2014
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Transformation from a film into a sphere, rapid merging of separate objects, controlled self-rotation, and planar locomotion are the very unusual phenomena observed in liquid metals under application of an electric field to a liquid metal immersed in or sprayed with water. A mechanism for these effects is suggested and potential applications - for example the recovery of liquid metal previously injected into the body for therapeutic purposes - are outlined.
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Insight into insulin secretion from transcriptome and genetic analysis of insulin-producing cells of Drosophila.
Genetics
PUBLISHED: 02-20-2014
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Insulin-producing cells (IPCs) in the Drosophila brain produce and release insulin-like peptides (ILPs) to the hemolymph. ILPs are crucial for growth and regulation of metabolic activity in flies, functions analogous to those of mammalian insulin and insulin-like growth factors (IGFs). To identify components functioning in IPCs to control ILP production, we employed genomic and candidate gene approaches. We used laser microdissection and messenger RNA sequencing to characterize the transcriptome of larval IPCs. IPCs highly express many genes homologous to genes active in insulin-producing ?-cells of the mammalian pancreas. The genes in common encode ILPs and proteins that control insulin metabolism, storage, secretion, ?-cell proliferation, and some not previously linked to insulin production or ?-cell function. Among these novelties is unc-104, a kinesin 3 family gene, which is more highly expressed in IPCs compared to most other neurons. Knockdown of unc-104 in IPCs impaired ILP secretion and reduced peripheral insulin signaling. Unc-104 appears to transport ILPs along axons. As a complementary approach, we tested dominant-negative Rab genes to find Rab proteins required in IPCs for ILP production or secretion. Rab1 was identified as crucial for ILP trafficking in IPCs. Inhibition of Rab1 in IPCs increased circulating sugar levels, delayed development, and lowered weight and body size. Immunofluorescence labeling of Rab1 showed its tight association with ILP2 in the Golgi of IPCs. Unc-104 and Rab1 join other proteins required for ILP transport in IPCs.
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Pulmonary toxicity in mice following exposure to cerium chloride.
Biol Trace Elem Res
PUBLISHED: 02-17-2014
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The widespread application of lanthanoids (Lns) in manufacturing industries has raised occupational and environmental health concerns about the possible increased health risks to humans exposed to Lns in their working and living environments. Numerous studies have shown that exposures to Ln cause pulmonary injury in animals, but very little is known about the molecular mechanisms of the pulmonary inflammation caused by cerium chloride (CeCl3) exposure. In this study, we evaluated the oxidative stress and molecular mechanism underlying with the pulmonary inflammation associated with chronic lung toxicity in mice treated with nasally instilled CeCl3 for 90 consecutive days. Our findings suggest that significant cerium accumulated in the lung, leading the obvious increase of the lung indices, significant increases in inflammatory cells and levels of lactate dehydrogenase, alkaline phosphate, and total protein, overproduction of reactive oxygen species and peroxidation of lipids, reduced antioxidant capacity, and pulmonary inflammation. CeCl3 exposure also activated nuclear factor ?B, increased the expression of tumor necrosis factor ?, cyclooxygenase-2, heme oxygenase 1, interleukin 2, interleukin 4, interleukin 6, interleukin 8, interleukin 10, interleukin 18, interleukin 1?, and CYP1A1. However, CeCl3 reduced the expression of nuclear factor ?B (NF-?B)-inhibiting factor and heat shock protein 70. These findings suggest that the pulmonary inflammation caused by CeCl3 in mice is closely associated with oxidative stress and inflammatory cytokine expression.
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Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.
BMC Nephrol
PUBLISHED: 02-14-2014
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Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.
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Factors predicting recurrence and postrecurrence survival in completely resected thymic carcinoma.
Ann. Thorac. Surg.
PUBLISHED: 02-12-2014
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There are few data on factors predicting recurrence of completely resected thymic carcinoma. This study analyzed prognosticators for recurrence and postrecurrence survival.
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Photomodulated fluorescence of supramolecular assemblies of sulfonatocalixarenes and tetraphenylethene.
ACS Nano
PUBLISHED: 02-05-2014
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Self-assembled fluorescent nanoparticles responding to specific stimuli are highly appealing for applications such as labels, probes, memory devices, and logic gates. However, organic analogues are challenging to prepare, due to unfavorable aggregation-caused quenching. We herein report the preparation of self-assembled fluorescent organic nanoparticles in water by means of calixarene-induced aggregation of a tetraphenylethene derivative (QA-TPE) mediated by p-sulfonatocalix[4]arenes. The self-assembled nanoparticles showed interesting photoswitching behaviors, and the fluorescence output of the generated nanoparticles was opposite to that of free QA-TPE both before and after irradiation. Free QA-TPE is nonfluorescent, owing to intramolecular rotations of the phenyl rings. In contrast, the self-assembled nanoparticles that formed upon complexation of QA-TPE with p-sulfonatocalix[4]arene exhibited aggregation-induced emission fluorescence (?(em) = 480 nm, ? = 14%), as a result of the inhibition of rotations. Upon UV light irradiation, free QA-TPE was cyclized to the corresponding diphenylphenanthrene, which showed typical fluorescence of a ?-conjugated system (?(em) = 385 nm, ? = 9.3%), whereas the nanoparticles were nonfluorescent upon irradiation due to the aggregation-caused quenching. In effect, this system allows programmed modulation of TPE fluorescence at two different emission wavelengths by means of host-guest complexation and irradiation. Relative to a single-mode stimulus-responsive system, our new developed system of highly integrated modes into a single molecular unit that can exhibit modulation of fluorescence by multiple stimulus is expected to be more adaptable for practical applications and to show enhanced multifunctionality.
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Decline in the incidence of invasive pneumococcal disease at a medical center in Taiwan, 2000-2012.
BMC Infect. Dis.
PUBLISHED: 02-04-2014
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It is essential to investigate the serotype distribution of pneumococcal diseases in each region and its associated clinical features. This study investigated the annual incidence of invasive pneumococcal disease (IPD) and the distribution of serotypes of isolates causing IPD at a medical center in northern Taiwan during the period 2000 to 2012.
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Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.
J. Assist. Reprod. Genet.
PUBLISHED: 01-25-2014
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Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL.
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TiO2 nanoparticles induced hippocampal neuroinflammation in mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Titanium dioxide nanoparticles (TiO2 NPs) have been used in various medical and industrial areas. However, the impacts of these nanoparticles on neuroinflammation in the brain are poorly understood. In this study, mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days, and the TLRs/TNF-?/NF-?B signaling pathway associated with the hippocampal neuroinflammation was investigated. Our findings showed titanium accumulation in the hippocampus, neuroinflammation and impairment of spatial memory in mice following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly activated the expression of Toll-like receptors (TLR2, TLR4), tumor necrosis factor-?, nucleic I?B kinase, NF-?B-inducible kinase, nucleic factor-?B, NF-?B2(p52), RelA(p65), and significantly suppressed the expression of I?B and interleukin-2. These findings suggest that neuroinflammation may be involved in TiO2 NP-induced alterations of cytokine expression in mouse hippocampus. Therefore, more attention should be focused on the application of TiO2 NPs in the food industry and their long-term exposure effects, especially in the human central nervous system.
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Real-time electrochemical recording of dopamine release under optogenetic stimulation.
PLoS ONE
PUBLISHED: 01-01-2014
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Dopaminergic PC12 cells can synthesize and release dopamine, providing a good cellular model for investigating dopamine regulation. Optogenetic stimulation of channelrhodopsin-2 provides high spatial and temporal precision for selective stimulation as a powerful neuromodulation tool for neuroscience studies. The aim of this study is to measure dopamine release from dopaminergic PC12 cells under optogenetic stimulation using electrochemical recording of self-assembled monolayers modified microelectrode with amperometric measurement in real time. The activation of PC12 cells under various optogenetic stimulation schemes are characterized by measuring single-cell Ca(2+) imaging. After 10 seconds of optogenetic stimulation, the evoked intracellular Ca(2+) level and dopamine current of channelrhodopsin-2-transfected PC12 cells were 1.6- and 3.5-fold higher than those of the control cells. The optogenetic stimulation effects on Ca(2+) influx and dopamine release were 81% and 63% inhibition by using a Ca(2+) channel antagonist Nifedipine. The results indicate that optogenetic stimulation can evoke voltage-gated Ca(2+) channel-dependent dopamine exocytosis from PC12 cells in a cell specific, temporally precise and dose-dependent manner. This proposed dopamine recording system can be developed to be a good cell model for dopamine regulation and drug screening in vitro, or dopaminergic cell implantation therapy in vivo using optogenetic stimulation in a precise and convenient way.
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Titanium Dioxide Nanoparticles Relieve Silk Gland Damage and Increase Cocooning of Bombyx mori under Phoxim-Induced Toxicity.
J. Agric. Food Chem.
PUBLISHED: 12-05-2013
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Organophosphate pesticides are applied widely in the world for agricultural purposes, and their exposures often resulted in non-cocooning of Bombyx mori in China. TiO2 nanoparticles have been demonstrated to increase pesticide resistance of Bombyx mori. While the toxicity of phoxim is well-documented, very limited information exists on the mechanisms of TiO2 nanoparticles improving the cocooning function of Bombyx mori following exposure to phoxim. The present study was, therefore, undertaken to determine whether TiO2 nanoparticles attenuate silk gland injury and elevate cocooning of B. mori following exposure to phoxim. The findings suggested that phoxim exposure resulted in severe damages of the silk gland structure and significantly decreased the cocooning in the silk gland of Bombyx mori. Furthermore, phoxim exposure significantly resulted in reductions of total protein concentrations and suppressed expressions of silk protein synthesis-related genes, including Fib-L, Fib-H, P25, Ser-2, and Ser-3, in the silk gland. TiO2 nanoparticle pretreatment, however, could significantly relieve silk gland injury of Bombyx mori. Importantly, TiO2 nanoparticles could remarkably elevate cocooning and total protein contents and promote expressions of Fib-L, Fib-H, P25, Ser-2, and Ser-3 in the silk gland following exposure to phoxim.
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Increasing incidence and lifetime risk of inflammatory bowel disease in Taiwan: a nationwide study in a low-endemic area 1998-2010.
Inflamm. Bowel Dis.
PUBLISHED: 10-22-2013
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The incidence of inflammatory bowel disease is increasing worldwide, but data of epidemiological trends from low-endemic area are limited. As one of the low-endemic countries, we describe the trends of this disease in Taiwan over time.
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Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle-attenuated damage in Bombyx mori.
Chemosphere
PUBLISHED: 10-04-2013
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Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China, however, exposure to this pesticide can result in a significant reduction in cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs) have been shown to decrease phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland damage due to OP exposure and repair of gland damage by TiO2 NP pretreatment. In the present study, exposure to phoxim resulted in a significant reduction in cocooning rate in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland damage, increased the antioxidant capacity of the gland, and increased cocooning rate in B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant alterations in the expression of 833 genes. In particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2, Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of both phoxim and TiO2 NP treatment resulted in marked changes in the expression of 754 genes, while treatment with TiO2 NPs led to significant alterations in the expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L, Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3, P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in B. mori caused by phoxim exposure.
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Ultrasound signal wavelet analysis to quantify the microstructures of normal and frozen tissues in vitro.
Cryobiology
PUBLISHED: 09-27-2013
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Cryosurgery has a number of advantages that make it particularly appealing in the treatment of liver cancer. However, a major problem for the wide clinical adoption of hepatic cryosurgery is the lack of a cost effective high resolution imaging way which is capable of both performing precise monitoring of the freezing process in situ and evaluating the postoperative effects after surgery. The mean scatterer spacing has been found to be an important parameter for describing the ultrasonic scattering and characterization of biological tissues. However, its potential values in the evaluation of cryosurgical effects of tissues reserved unclear so far. Here, we investigated the wavelet analysis to estimate the mean scatterer spacing parameter in normal and freeze-thawed tissues on porcine livers in vitro. The experimental results carried out at 10MHz using weakly focused pulse-echo signal element transducer indicated that the mean scatterer spacing in normal liver tissues is 1.12±0.13mm whereas it is 1.67±0.25mm in several pre-frozen and then thawed tissues. These results disclosed the good correlation between the wavelet data and microstructures of the normal or thawed tissues, and hence demonstrated that the wavelet analysis holds promise to be used as an effective method for the characterization of thawed tissues scatterer spacing. The present method offers a potential pragmatic strategy for monitoring the transition zone between frozen and unfrozen tissues during the surgical therapy, and evaluating postoperative effects.
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[Research on the effect of extract of dentin matrix on the differentiation of dental pulp cells].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-25-2013
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To investigate the effects of human treated dentin matrix (hTDM) extracellular matrix molecules on odontogenetic and neural differentiation of human dental pulp cells (hDPCs) with an aim to find an effective method to collect extracellular matrix molecules to contribute to reparation dental-pulp complex with dentin defects.
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Mechanisms of larval midgut damage following exposure to phoxim and repair of phoxim-induced damage by cerium in Bombyx mori.
Environ. Toxicol.
PUBLISHED: 09-18-2013
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Bombyx mori is an important economic animal for silk production. However, it is liable to be infected by organophosphorus pesticide that can contaminate its food and growing environment. It has been known that organophosphorus pesticide including phoxim exposure may damage the digestive systems, produce oxidative stress and neurotoxicity in silkworm B. mori, whereas cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori. However, very little is known about the molecular mechanisms of midgut injury due to phoxim exposure and B. mori protection after cerium pretreatment. The aim of this study was to evaluate the midgut damage and its molecular mechanisms, and the protective role of cerium in B. mori following exposure to phoxim. The results showed that phoxim exposure led to severe midgut damages and oxidative stress; whereas cerium relieved midgut damage and oxidative stress caused by phoxim in B. mori. Furthermore, digital gene expression suggested that phoxim exposure led to significant up-regulation of 94 genes and down-regulation of 52 genes. Of these genes, 52 genes were related with digestion and absorption, specifically, the significant alterations of esterase, lysozyme, amylase 48, and lipase expressions. Cerium pretreatment resulted in up-regulation of 116 genes, and down-regulation of 29 genes, importantly, esterase 48, lipase, lysozyme, and ?-amylase were up-regulated. Treatment with Phoxim + CeCl3 resulted in 66 genes up-regulation and 39 genes down-regulation; specifically, levels of esterase 48, lipase, lysozyme, and ?-amylase expression in the midgut of silkworms were significantly increased. Therefore, esterase 48, lipase, lysozyme, and ?-amylase may be potential biomarkers of midgut toxicity caused by phoxim exposure. These findings may expand the application of rare earths in sericulture. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
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Immunomodulatory effects in the spleen-injured mice following exposure to titanium dioxide nanoparticles.
J Biomed Mater Res A
PUBLISHED: 09-12-2013
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Immune injuries following the exposure of titanium dioxide nanoparticles (TiO2 NPs) have been greatly concerned along with the TiO2 NPs are widely used in pharmacology and daily life. However, very little is known about the immunomodulatory mechanisms in the spleen-injured mice due to TiO2 NPs exposure. In this study, mice were continuously exposed to 2.5, 5, or 10 TiO2 NPs mg kg(-1) body weight for 90 days with intragastric administration to investigate the immunomodulatory mechanisms in the spleen. The findings showed that TiO2 NPs exposure resulted in significant increases in spleen and thymus indices, and titanium accumulation, in turn led to histopathological changes and splenocyte apoptosis. Furthermore, the exposure of TiO2 NPs could significantly increase the levels of macrophage inflammatory protein (MIP)-1?, MIP-2, Eotaxin, monocyte chemotactic protein-1, interferon-?, vascular cell adhesion molecule-1, interleukin-13, interferon-?-inducible protein-10, migration inhibitory factor, CD69, major histocompatibility complex, protein tyrosine phosphatase, protein tyrosine kinase 1, basic fibroblast growth factor, Fasl, and GzmB expression, whereas markedly decrease the levels of NKG2D, NKp46, 2B4 expression involved in immune responses, lymphocyte healing and apoptosis. These findings would better understand toxicological effects induced by TiO2 NPs exposure. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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Renal injury and Nrf2 modulation in mouse kidney following chronic exposure to TiO? nanoparticles.
J. Agric. Food Chem.
PUBLISHED: 09-06-2013
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TiO? nanoparticles (NPs) are used in the food industry but have potential toxic effects in humans and animals. TiO? NPs impair renal function and cause oxidative stress and renal inflammation in mice, associated with inhibition of nuclear factor erythroid-2-related factor 2 (Nrf2), which regulates genes encoding many antioxidants and detoxifying enzymes. This study determined whether TiO? NPs activated the Nrf2 signaling pathway. Mice exhibited accumulation of reactive oxygen species and peroxidation of lipid, protein, and DNA in the kidney, coupled with renal dysfunction, glutathione depletion, inflammatory cell infiltration, fatty degeneration, and apoptosis. These were associated with increased expression of NOX4, cyclooxygenase-2, and nuclear factor-?B. Oxidative stress and inflammation were accompanied by decreased expression of Nrf2 and down-regulation of its target gene products including heme oxygenase 1, glutamate-cysteine ligase catalytic subunit, and glutathione S-transferase. Chronic TiO? NP exposure is associated with suppression of Nrf2, which contributes to the pathogenesis of oxidative stress and inflammation.
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Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO2 nanoparticles.
J. Hazard. Mater.
PUBLISHED: 08-04-2013
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Due to the increased application of titanium dioxide nanoparticles (TiO2 NPs) in various areas, numerous studies have been conducted which have confirmed that exposure to TiO2 NPs may result in neurological damage in both mice and rats. However, very few studies have focused on the molecular mechanisms of spatial recognition injury. In the present study, to understand the possible neurobiological responses of the mouse hippocampus following subchronic peroral exposure to low level TiO2 NPs, mice were exposed to 2.5, 5, and 10mg/kg body weight TiO2 NPs for 90 consecutive days. Hippocampal pathology and neuron ultrastructure, and long-term potentiation (LTP) were then evaluated, and the hippocampal mRNA-expression of several genes and their proteins involved in homeostasis of neuronal synaptic plasticity were investigated using a quantitative real-time PCR and ELISA method. We observed that subchronic peroral exposure to TiO2 NPs caused severe pathological changes, spatial recognition impairment, and resulted in significant LTP reduction and down-regulation of N-methyl-D-aspartate (NMDA) receptor subunits (NR2A and NR2B) expression associated with the simultaneous inhibition of CaMKIV, cyclic-AMP responsive element binding proteins (CREB-1, CREB-2), and FosB/DFosB in mouse hippocampal tissues. Therefore, our findings suggest that the application of TiO2 NPs in the various areas should be paid more attention.
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Application of dissolvable layered double hydroxides as sorbent in dispersive solid-phase extraction and extraction by co-precipitation for the determination of aromatic acid anions.
Anal. Chem.
PUBLISHED: 07-29-2013
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Three types of magnesium-aluminum layered double hydroxides were synthesized and employed as solid-phase extraction (SPE) sorbents to extract several aromatic acids (protocatechuic acid, mandelic acid, phthalic acid, benzoic acid, and salicylic acid) from aqueous samples. An interesting feature of these sorbents is that they dissolve when the pH of the solution is lower than 4. Thus, the analyte elution step, as needed in conventional sorbent-based extraction, was obviated by dissolving the sorbent in acid after extraction and separation from the sample solution. The extract was then directly injected into a high-performance liquid chromatography-ultraviolet detection system for analysis. In the key adsorption process, both dispersive SPE and co-precipitation extraction with the sorbents were conducted and experimental parameters such as pH, temperature, and extraction time were optimized. The results showed that both extraction methods provided low limits of detection (0.03-1.47 ?g/L) and good linearity (r(2) > 0.9903). The optimized extraction conditions were applied to human urine and sports drink samples. This new and interesting extraction approach was demonstrated to be a fast and efficient procedure for the extraction of organic anions from aqueous samples.
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Molecular mechanism of oxidative damage of lung in mice following exposure to lanthanum chloride.
Environ. Toxicol.
PUBLISHED: 07-27-2013
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Exposure to lanthanoids (Ln) elicits an adverse response such as oxidative injury of lung in animals and human. The molecular targets of Ln remain unclear. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in LaCl3 -induced oxidative stress in mouse lung were investigated. Mice were exposed to 2, 5, and 10 mg/kg body weight by nasal administration for 6 consecutive months. With increased doses, La was markedly accumulated and promoted the reactive oxygen species (ROS) production in the lung, which in turn resulted in peroxidation of lipids, proteins and DNA, and severe pulmonary damages. Furthermore, LaCl3 exposure could significantly increase levels of Nrf2, heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC) expressions in the LaCl3 -exposed lung. These findings imply that the induction of Nrf2 expression is an adaptive intracellular response to LaCl3 -induced oxidative stress in mouse lung, and that Nrf2 may regulate the LaCl3 -induced pulmonary damages. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
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Accurate estimation of human body orientation from RGB-D sensors.
IEEE Trans Cybern
PUBLISHED: 07-23-2013
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Accurate estimation of human body orientation can significantly enhance the analysis of human behavior, which is a fundamental task in the field of computer vision. However, existing orientation estimation methods cannot handle the various body poses and appearances. In this paper, we propose an innovative RGB-D-based orientation estimation method to address these challenges. By utilizing the RGB-D information, which can be real time acquired by RGB-D sensors, our method is robust to cluttered environment, illumination change and partial occlusions. Specifically, efficient static and motion cue extraction methods are proposed based on the RGB-D superpixels to reduce the noise of depth data. Since it is hard to discriminate all the 360 (°) orientation using static cues or motion cues independently, we propose to utilize a dynamic Bayesian network system (DBNS) to effectively employ the complementary nature of both static and motion cues. In order to verify our proposed method, we build a RGB-D-based human body orientation dataset that covers a wide diversity of poses and appearances. Our intensive experimental evaluations on this dataset demonstrate the effectiveness and efficiency of the proposed method.
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Enzyme-responsive supramolecular polymers by complexation of bis(p-sulfonatocalixarenes) with suberyl dicholine-based pseudorotaxane.
Chem. Commun. (Camb.)
PUBLISHED: 06-21-2013
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A linear supramolecular ternary polymer was fabricated by iteratively threading cyclodextrin with suberyl dicholine and end-capping with bis-calixarenes, showing desired cholinesterase response.
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Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 06-10-2013
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To investigate the clinical characteristics of Clostridium difficile infection (CDI) at a medical center in Taiwan.
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Toxicological mechanisms of nanosized titanium dioxide-induced spleen injury in mice after repeated peroral application.
J. Agric. Food Chem.
PUBLISHED: 05-29-2013
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Due to an increase in surface area per particle weight, nanosized titanium dioxide (nano-TiO2) has greatly increased its function as a catalyst and is used for whitening and brightening foods. However, concerns over the safety of nano-TiO2 have been raised. The purpose of this study was to determine whether the protein kinase MAPKs/PI3-K/Akt signaling pathways and transcription factors are activated prior to or concurrent with COX-2 up-regulation in mouse spleen following exposure to 10 mg/kg BW of pure anatase nano-TiO2 by the intragastric route for 15-90 days. The study clearly showed that nano-TiO2 was deposited in the spleen and resulted in reactive oxygen species production, time-dependent splenic inflammation, and necrosis, coupled with a 12.64-64.06% increase in COX-2 and prostaglandin E2 expression, respectively. Furthermore, nano-TiO2 elevated the expressions of ERK, AP-1, CRE, Akt, JNK2, MAPKs, PI3-K, c-Jun, and c-Fos in the spleen by 1.08-6-fold with increased exposure duration, respectively. These findings suggested that nano-TiO2-induced COX-2 expression may be mediated predominantly through the induction of AP-1 and CRE and that AP-1/CRE induction occurred via the MAPKs/PI3-K/Akt signaling pathways in the spleen. Therefore, the findings suggest the need for caution when using nanomaterials as food additives.
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Synthesis and biological evaluation of N-substituted sophocarpinic acid derivatives as coxsackievirus?B3 inhibitors.
ChemMedChem
PUBLISHED: 05-20-2013
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A series of novel N-substituted sophocarpinic acid derivatives was designed, synthesized, and evaluated for their anti-enteroviral activities against coxsackievirus type?B3 (CVB3) and coxsackievirus type?B6 (CVB6) in Vero cells. Structure-activity relationship analysis revealed that the introduction of a benzenesulfonyl moiety on the 12-nitrogen atom in (E)-?,?-sophocarpinic acid might significantly enhance anti-CVB3 activity. Among the derivatives, (E)-12-N-(m-cyanobenzenesulfonyl)-?,?-sophocarpinic acid (11?m), possessing a meta-cyanobenzenesulfonyl group, exhibited potent activity against CVB3 with a selectivity index (SI) of 107. Furthermore, compound 11?m also showed a good oral pharmacokinetic profile, with an AUC value of 7.29??M?h?¹ in rats, and good safety through the oral route in mice, with an LD?? value of >1000?mg?kg?¹; these values suggest a druggable characteristic. Therefore, compound 11?m was selected for further investigation as a promising CVB3 inhibitor. We consider (E)-?,?-N-(benzenesulfonyl)sophocarpinic acids to be a novel class of anti-CVB3 agents.
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Oxidative stress in the kidney injury of mice following exposure to lanthanides trichloride.
Chemosphere
PUBLISHED: 05-17-2013
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Environmental pollution from lanthanides (Ln) has been recognized as a major problem due to a grab exploitation of Ln mine in China. Exposure to Ln has been demonstrated to cause the nephrotoxicity, very little is known about the mechanism of oxidative damage to kidney in animals. In order to understand Ln-induced nephrotoxicity, various biochemical and chemical parameters were assayed in mouse kidney. Intragastric exposures of LaCl?, CeCl?, and NdCl? at doses of 2, 5, and 10 mg kg(-1) BW for 90 consecutive days caused nephritis or epithelial cell necrosis and oxidative stress to kidney. An increase in coefficients of the kidney, La, Ce, and Nd accumulation and histopathological changes in the kidney could be observed, followed by increased reactive oxygen species production and peroxidation levels of lipid, protein and DNA, and decreased activities of superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase as well as antioxidants such as glutathione, ascorbic acid and thiol contents. Furthermore, La, Ce, and Nd significantly suppressed expression of genes and proteins of these antioxidative enzymes in mouse kidney. In addition, kidney functions were disrupted, including an increase of the creatinine, and reductions of uric acid, urea nitrogen, calcium and phosphonium. These findings suggest that nephritis generation or epithelial cell necrosis in mice following exposure to Ln is closely associated with oxidative stress. Of these damages, the most severe was in the Ce(3+)-exposed kidneys, next in the Nd(3+)-exposed kidneys, and the least in the La(3+)-exposed kidneys, which may be attributed to the 4f electron of Ln.
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Genome-wide identification and expression profiling of ankyrin-repeat gene family in maize.
Dev. Genes Evol.
PUBLISHED: 05-08-2013
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Members of the ankyrin repeats (ANK) gene family encode ANK domain that are common in diverse organisms and play important roles in cell growth and development, such as cell-cell signal transduction and cell cycle regulation. Recently, genome-wide identification and evolutionary analyses of the ANK gene family have been carried out in Arabidopsis and rice. However, little is known regarding the ANK genes in the entire maize genome. In this study, we described the identification and structural characterization of 71 ANK genes in maize (ZmANK). Then, comprehensive bioinformatics analyses of ZmANK genes family were performed including phylogenetic, domain and motif analysis, chromosomal localization, intron/exon structural patterns, gene duplications and expression profiling. Domain composition analyses showed that ZmANK genes formed ten subfamilies. Five tandem duplications and 14 segmental duplications were identified in ZmANK genes. Furthermore, we took comparative analysis of the total ANK gene family in Arabidopsis, rice and maize, ZmANKs were more closely paired with OsANKs than with AtANKs. At last, expression profile analyses were performed. Forty-one members of ZmANK genes held EST sequences records. Semi-quantitative expression and microarray data analysis of these 41 ZmANK genes demonstrated that ZmANK genes exhibit a various expression pattern, suggesting that functional diversification of ZmANK genes family. The results will present significant insights to explore ANK genes expression and function in future studies in maize.
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Pharmacological and physical prevention and treatment of no-reflow after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction.
J. Int. Med. Res.
PUBLISHED: 04-29-2013
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After successful primary percutaneous coronary intervention in ST-segment elevation myocardial infarction, adequate myocardial reperfusion is not achieved in up to 50% of patients. This phenomenon of no-reflow is associated with a poor in-hospital and long-term prognosis. Four main factors are thought to contribute to the occurrence of no-reflow: ischaemic injury; reperfusion injury; distal embolization; susceptibility of the microcirculation to injury. This review evaluates the literature, and in particular the clinical trials, concerned with pharmacological and physical methods for prevention and treatment of no-reflow. A number of drugs may improve no-reflow experimentally and clinically, but some have not yet been associated with conclusive improvements in clinical outcome. The complex interacting factors in no-reflow make it unlikely that any single agent will be effective for all patients. Confirmed methods known to be beneficial in the prevention of no-reflow (such as aspirin therapy, chronic statin therapy, blood glucose control, thrombus aspiration in patients with a high thrombus burden and ischaemic preconditioning) should be offered to patients as often as possible, to prevent and treat no-reflow.
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Titanium dioxide nanoparticle-induced testicular damage, spermatogenesis suppression, and gene expression alterations in male mice.
J. Hazard. Mater.
PUBLISHED: 04-21-2013
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Although titanium dioxide nanoparticles (TiO2 NPs) have been demonstrated to accumulate in organs resulting in toxicity, there is currently only limited data regarding male reproductive toxicity by TiO2 NPs. In this study, testicular damage and alterations in gene expression profiles in male mice induced by intragastric administration of 2.5, 5, and 10mg/kg body weight of TiO2 NPs for 90 consecutive days were examined. Our findings showed that TiO2 NPs can cross the blood-testis barrier to reach the testis and accumulate therein, which, in turn, results in testicular lesions, sperm malformations, and alterations in serum sex hormone levels. Furthermore, microarray analysis showed that 70 genes with known functions were up-regulated, while 72 were down-regulated in TiO2 NPs-exposed testes. Of the altered gene expressions, Ly6e, Adam3, Tdrd6, Spata19, Tnp2, and Prm1 are involved in spermatogenesis, whereas Sc4mol, Psmc3ip, Mvd, Srd5a2, Lep, and Cyp2e1 are associated with steroid and hormone metabolism. Hence, the production and application of TiO2 NPs should be carried out cautiously, especially by humans of reproductive age.
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Kidney injury and alterations of inflammatory cytokine expressions in mice following long-term exposure to cerium chloride.
Environ. Toxicol.
PUBLISHED: 04-15-2013
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It has been demonstrated that the organic damages of animals can be caused by exposure to lanthanide oxides or compounds. However, the molecular mechanism of CeCl3 -induced kidney injury remains unclear. In this study, the mechanism of nephric damage in mice induced by an intragastric administration of CeCl3 was investigated. The results showed that Ce(3+) was accumulated in the kidney, which in turn led to oxidative stress, severe nephric inflammation, and dysfunction in mice. Furthermore, CeCl3 activated nucleic factor ?B, which in turn increased the expression levels of tumor necrosis factor ?, macrophage migration inhibitory factor, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1?, cross-reaction protein, transforming growth factor-?, interferon-?, and CYP1A1, while suppressed heat shock protein 70 expression. These findings implied that Ce(3+) -induced kidney injury of mice might be associated with oxidative stress, alteration of inflammatory cytokine expression, and reduction of detoxification of CeCl3 . © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
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[Differentiation treatment by all-trans retinoic acid reduces phenotype of glioma stem cells].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-13-2013
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To explore the effects of all-trans retinoic acid (ATRA) on glioma stem cell phenotype.
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Synthesis and structure-activity relationship of 8-substituted protoberberine derivatives as a novel class of antitubercular agents.
Chem Cent J
PUBLISHED: 04-01-2013
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The emergence of multi-drug resistant tuberculosis (MDR-TB) has heightened the need for new chemical classes and innovative strategies to tackle TB infections. It is urgent to discover new classes of molecules without cross-resistance with currently used antimycobacterial drugs.
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Therapeutic effects of thalidomide in hematologic disorders: a review.
Front Med
PUBLISHED: 03-07-2013
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The extensive autoimmune, anti-inflammatory, and anticancer applications of thalidomide have inspired a growing number of studies and clinical trials. As an inexpensive agent with relatively low toxicity, thalidomide is regarded as a promising therapeutic candidate, especially for malignant diseases. We review its therapeutic effects in hematology, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphoma, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graftversus-host disease. Most studies have shown satisfactory results, although several have reported the opposite. Aside from optimal outcomes, the toxicities and adverse effects of thalidomide should also be examined. The current work includes a discussion of the mechanisms through which the novel biological effects of thalidomide occur, although more studies should be devoted to this aspect. With appropriate safeguards, thalidomide may benefit patients suffering from a broad variety of disorders, particularly refractory and resistant diseases.
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