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Find video protocols related to scientific articles indexed in Pubmed.
Subtemporal-anterior transtentoral approach to middle cranial fossa microsurgical anatomy.
J Craniofac Surg
PUBLISHED: 11-08-2014
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This study aimed to describe the topography of inferior and external dura mater of the middle cranial fossa through subtemporal-anterior transpetrosal approach and discuss the feasibility of improving the approach. Eight formalin-fixed adult cadaveric heads were studied, with the bones milled away in the lateral triangle region of the petrous bone, Kawase rhombus region, and inner triangle region of the petrous apex. The distances between the targets in these regions, as well as the angles after the dissection of zygomatic arch, were measured, and then the exposed petroclival and retrochiasmatic areas were observed under the microscope. There were significant variations in the distances between targets in the 3 milled regions among the specimens. After the dissection of zygomatic arch, the surgical view got an average increase of 12 degrees. The subtemporal anterior transpetrosal approach, as an improved subtemporal approach, can expose the lesions optimally, causing no injury to the hearing and reducing injuries to temporal lobe. On the other hand, the lateral bone of the petrous parts of the temporal bone is removed so as to improve the view to the retrochiasmatic area and expand the operative field.
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Electronic Effects of Ring Fusion and Alkyne Substitution on Acene Properties and Reactivity.
J. Org. Chem.
PUBLISHED: 10-23-2014
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This paper describes the synthesis and systematic study of substituted acenes that have differences in conjugation both along their long axes (by the number of fused benzene or thiophene rings) and along their short axes (by the number of arylethynyl substituents). These acenes include what we believe to be the first reported examples of five new subclasses of substituted acenes. Systematic analyses of data obtained using absorbance and fluorescence spectroscopies, cyclic voltammetry, and DFT calculations reveal clear correlations between these common structural perturbations to acene structure and the key parameters, such as HOMO-LUMO gap, frontier molecular orbital energies, and reactivity with singlet oxygen.
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Selenium/interconnected porous hollow carbon bubbles composites as the cathodes of Li-Se batteries with high performance.
Nanoscale
PUBLISHED: 09-19-2014
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A kind of Se/C nanocomposite is fabricated by dispersing selenium in interconnected porous hollow carbon bubbles (PHCBs) via a melt-diffusion method. Such PHCBs are composed of porous hollow carbon spheres with a size of ?70 nm and shells of ?12 nm thickness interconnected to each other. Instrumental analysis shows that the porous shell of the PHCBs could effectively disperse and sequester most of the selenium, while the inner cavity remains hollow. When evaluated as cathode materials in a carbonate-based electrolyte for Li-Se batteries, the Se/PHCBs composites exhibit significantly excellent cycling performance and a high rate capability. Especially, the Se/PHCBs composite with an optimal content of ?50 wt% selenium (Se50/PHCBs) displays a reversible discharge capacity of 606.3 mA h g(-1) after 120 cycles at 0.1 C charge-discharge rate. As the current density increased from 0.1 to 1 C (678 mA g(-1)), the reversible capacity of the Se50/PHCBs composite can still reach 64% of the theoretical capacity (431.9 mA h g(-1)). These outstanding electrochemical features should be attributed to effective sequestration of Se in the PHCBs, as well as to the ability to accommodate volume variation and enhance the electronic transport by making Se have close contact with the carbon framework.
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Power spectral differences of electrophysiological signals detected at acupuncture points and non-acupuncture points.
Acupunct Electrother Res
PUBLISHED: 09-16-2014
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In this study, we chose 10 acupoints and non-acupuncture point control groups to see if there are electrical differences between acupoints and non-acupoints. 4 adjacent non-acupoints around each acupoint were chosen as a control group in 400 trials on 10 volunteers aged 23-30 years to characterize the Power Spectral Density of acupoint electrophysiological signals, which means the differences of power and its distribution in frequency. The electrophysiological signals of acupoints and control groups were recorded simultaneously. The results show that acupoint electrophysiological signals have higher Power Spectral Density and power than nearby non-acupoint areas. Integrating the entire data, power of acupoint electrical signals are about 14.7% higher than nearby non-acupoint electrical signals, and most of the higher power is distributed from 0 to 10 Hz and 0-2 Hz is the highest. The maximum power difference between acupoints and non-acupoint is 61.5% appeared in LI 11(see text for symbol). From physiological view, the percentage is high enough to show the electrical specificity of acupoint, which is strong proof of Traditional Chinese Medicine theory and one of the bases for further research. As acupoint electrophysiological signals are driven by internal organs, they can reflect the health condition of internal organs effectively, and so analysis of acupoint electrophysiological signals may be a new way to diagnose organ diseases instead of with the experience of doctor of Traditional Chinese Medicine.
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Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA.
Nucleic Acids Res.
PUBLISHED: 09-15-2014
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RNAi technology is taking strong position among the key therapeutic modalities, with dozens of siRNA-based programs entering and successfully progressing through clinical stages of drug development. To further explore potentials of RNAi technology as therapeutics, we engineered and tested VEGFR2 siRNA molecules specifically targeted to tumors through covalently conjugated cyclo(Arg-Gly-Asp-d-Phe-Lys[PEG-MAL]) (cRGD) peptide, known to bind ?v?3 integrin receptors. cRGD-siRNAs were demonstrated to specifically enter and silence targeted genes in cultured ?v?3 positive human cells (HUVEC). Microinjection of zebrafish blastocysts with VEGFR2 cRGD-siRNA resulted in specific inhibition of blood vessel growth. In tumor-bearing mice, intravenously injected cRGD-siRNA molecules generated no innate immune response and bio-distributed to tumor tissues. Continuous systemic delivery of two different VEGFR2 cRGD-siRNAs resulted in down-regulation of corresponding mRNA (55 and 45%) and protein (65 and 45%) in tumors, as well as in overall reduction of tumor volume (90 and 70%). These findings demonstrate strong potential of cRGD-siRNA molecules as anti-tumor therapy.
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A genome-wide detection of copy number variation using SNP genotyping arrays in Beijing-You chickens.
Genetica
PUBLISHED: 08-18-2014
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Copy number variation (CNV) has been recently examined in many species and is recognized as being a source of genetic variability, especially for disease-related phenotypes. In this study, the PennCNV software, a genome-wide CNV detection system based on the 60 K SNP BeadChip was used on a total sample size of 1,310 Beijing-You chickens (a Chinese local breed). After quality control, 137 high confidence CNVRs covering 27.31 Mb of the chicken genome and corresponding to 2.61 % of the whole chicken genome. Within these regions, 131 known genes or coding sequences were involved. Q-PCR was applied to verify some of the genes related to disease development. Results showed that copy number of genes such as, phosphatidylinositol-5-phosphate 4-kinase II alpha, PHD finger protein 14, RHACD8 (a CD8?- like messenger RNA), MHC B-G, zinc finger protein, sarcosine dehydrogenase and ficolin 2 varied between individual chickens, which also supports the reliability of chip-detection of the CNVs. As one source of genomic variation, CNVs may provide new insight into the relationship between the genome and phenotypic characteristics.
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Residents health risk of Pb, Cd and Cu exposure to street dust based on different particle sizes around zinc smelting plant, Northeast of China.
Environ Geochem Health
PUBLISHED: 08-13-2014
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The residents health risk of Pb, Cd and Cu exposure to street dust with different particle sizes (<100 and <63 ?m) near Huludao Zinc Plant (HZP) was investigated in this study. The average concentrations of Pb, Cd and Cu in the <100-?m and <63-?m dust were 1,559, 178.5, 917.9 and 2,099, 198.4, 1,038 mg kg(-1), respectively. It showed that smaller particles tended to contain higher element concentrations. Metals in dust around HZP decreased gradually from the zinc smelter to west and east directions. There was significantly positive correlation among Pb, Cd and Cu in street dust with different particle sizes. The contents of Pb, Cd and Cu in dust increased with decreasing pH or increasing organic matter. Non-carcinogenic health risk assessment showed that the health index (HI) for children and adult exposed to <63-?m particles were higher than exposed to <100-?m particles, which indicated that smaller particles tend to have higher non-carcinogenic health risk. Non-carcinogenic risk of Pb was the highest in both particle sizes, followed by Cd and Cu. HI for Pb and Cd in both particle sizes for children had exceeded the acceptable value, indicated that children living around HZP were experiencing the non-carcinogenic health risk from Pb and Cd exposure to street dust.
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Something between the amazing functions and various morphologies of self-assembling peptides materials in the medical field.
J Biomater Sci Polym Ed
PUBLISHED: 08-04-2014
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In recent years, there are a growing number of researches in the field of self-assembling peptides. Due to their diversity structures and the promising applications, self-assembling peptides have already become the focus of studies in the fields of materials and biological science. Some amazing functions of these peptides in the medical field caught our attention, such as tissue repair and regeneration, therapeutic delivery, haemostasis, antimicrobial and so on. There are different morphologies of self-assembling peptides in different functions. This review provides an overview of the relationship between some amazing functions and various morphologies of self-assembling peptides principally. Furthermore, the mechanisms of peptide self-assembly are also discussed.
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Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2 gene for tumor therapy.
Int J Nanomedicine
PUBLISHED: 07-29-2014
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The clinical application of small interfering RNA (siRNA) has been restricted by their poor intracellular uptake, low serum stability, and inability to target specific cells. During the last several decades, a great deal of effort has been devoted to exploring materials for siRNA delivery. In this study, biodegradable, tumor-targeted, self-assembled peptide nanoparticles consisting of cyclo(Arg-Gly-Asp-d-Phe-Lys)-8-amino-3,6-dioxaoctanoic acid-?-maleimidopropionic acid (hereafter referred to as RPM) were found to be an effective siRNA carrier both in vitro and in vivo. The nanoparticles were characterized based on transmission electron microscopy, circular dichroism spectra, and dynamic light scattering. In vitro analyses showed that the RPM/VEGFR2-siRNA exhibited negligible cytotoxicity and induced effective gene silencing. Delivery of the RPM/VEGFR2 (zebrafish)-siRNA into zebrafish embryos resulted in inhibition of neovascularization. Administration of RPM/VEGFR2 (mouse)-siRNA to tumor-bearing nude mice led to a significant inhibition of tumor growth, a marked reduction of vessels, and a down-regulation of VEGFR2 (messenger RNA and protein) in tumor tissue. Furthermore, the levels of IFN-?, IFN-?, IL-12, and IL-6 in mouse serum, assayed via enzyme-linked immunosorbent assay, did not indicate any immunogenicity of the RPM/VEGFR2 (mouse)-siRNA in vivo. In conclusion, RPM may provide a safe and effective delivery vector for the clinical application of siRNAs in tumor therapy.
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Synthesis and characterization of hyaluronic acid/human-like collagen hydrogels.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 07-27-2014
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Injectable hydrogel plays an important role in soft tissue filling and repair. We report an injectable hydrogel based on hyaluronic acid (HA) and human-like collagen (HLC), both with favorable biocompatibility and biodegradability. These two types of biomacromolecules were crosslinked with 1,4-butanediol diglycidyl ether to form a three-dimensional network. The redundant crosslinker was removed by dialysis and distillation. An HA-based hydrogel prepared by the same method was used as a control. The cytocompatibility was studied with a Cell Counting Kit-8 (CCK-8) test. Carbazole colorimetry was used to analyze the in vitro degradation rate. The histocompatibility was evaluated by hematoxylin and eosin (H&E) staining analysis and immunohistochemical analysis. The CCK-8 assay demonstrated that the HA/HLC hydrogel was less cytotoxic than the HA-based hydrogel and could promote baby hamster kidney cell (BHK) proliferation. The cell adhesion indicated that BHK could grow well on the surface of the materials and maintain good cell viability. The in vitro degradation test showed that the HA/HLC hydrogel had a longer degradation time and an excellent antienzyme ability. In vivo injection showed that there was little inflammatory response to HA/HLC after 1, 2, and 4 weeks. Therefore, the HA/HLC hydrogel is a promising biomaterial for soft tissue filling and repair.
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Comparative study of corneal endothelial cell damage after femtosecond laser assisted deep stromal dissection.
Biomed Res Int
PUBLISHED: 07-10-2014
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To find a relatively safe designed stromal bed thickness to avoid endothelial damage for lamellar keratoplasty with an Allegretto Wavelight FS200 femtosecond laser.
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Interferon-? Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis.
Am. J. Pathol.
PUBLISHED: 06-24-2014
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The function of blood-brain barrier is often disrupted during the progression of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the molecular mechanism of blood-brain barrier modulation during neuroinflammation remains unclear. Herein, we show that the expression of interferon-? (IFN?) receptor on endothelial cells (ECs) protected mice from the brain inflammation during EAE. IFN? stabilized the integrity of the cerebral endothelium and prevented the infiltration of leukocytes into the brain. Further analysis revealed that IFN? increased the expression of tight junction proteins zonula occludens protein 1 and occludin, as well as membranous distribution of claudin-5, in brain ECs. Silencing claudin-5 abolished the IFN?-mediated improvement of EC integrity. Taken together, our results show that IFN?, a pleiotropic proinflammatory cytokine, stabilizes blood-brain barrier integrity and, therefore, prevents brain inflammation during EAE.
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Effects of p75 neurotrophin receptor on regulating hypoxia-induced angiogenic factors in retinal pigment epithelial cells.
Mol. Cell. Biochem.
PUBLISHED: 06-22-2014
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Retinal pigment epithelium (RPE) exerts critical roles in the maintenance of the normal functions of the retina, whereas RPE dysfunction can induce retina neovascularization. p75 neurotrophin receptor (p75(NTR)) has been shown to play essential roles in angiogenesis. However, the function of p75(NTR) in the RPE remains unclear. In the present study, we demonstrated that p75(NTR) was highly expressed in the human choroidal neovascularization membranes. For in vitro study, RPE was exposed to hypoxia, and a knockdown of p75(NTR) was achieved via lentivirus-mediated RNA interference. The results showed that hypoxia induced the expression of p75(NTR) in the RPE, and the knockdown of p75(NTR) rescued RPE proliferation activity and inhibited apoptosis which induced by hypoxia. After the deletion of p75(NTR), RPE-secreted pro-angiogenic factors (vascular endothelial growth factor and platelet-derived growth factor), inflammatory factors [interleukin 1 beta (IL1?), IL18, and stromal cell-derived factor 1], and matrix metalloproteinases (MMPs) (MMP3 and MMP9) were down-regulated under hypoxic conditions. While the RPE secreted anti-angiogenic factors (pigment epithelium-derived factor) and angiostatin, the tissue inhibitors of metalloproteinases (TIMPs) (TIMP-1 and TIMP-3) were up-regulated after the knockdown of p75(NTR). The human umbilical vein endothelial tube formation ability can be inhibited when it is co-cultured with the supernatant extract from p75(NTR)-knockdown RPE under hypoxic induction. These results suggest that the knockdown of p75(NTR) suppressed pro-angiogenic factors which induced by hypoxia while promoting the anti-angiogenesis-related factors in the RPE. It is indicated that p75(NTR) could be a potential therapeutic target for RPE hypoxia or oxidative stress diseases.
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Regulation of lncRNA expression.
Cell. Mol. Biol. Lett.
PUBLISHED: 06-19-2014
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Long non-coding RNAs (lncRNAs) are series of transcripts with important biological functions. Various diseases have been associated with aberrant expression of lncRNAs and the related dysregulation of mRNAs. In this review, we highlight the mechanisms of dynamic lncRNA expression. The chromatin state contributes to the low and specific expression of lncRNAs. The transcription of non-coding RNA genes is regulated by many core transcription factors applied to protein-coding genes. However, specific DNA sequences may allow their unsynchronized transcription with their location-associated mRNAs. Additionally, there are multiple mechanisms involved in the post-transcriptional regulation of lncRNAs. Among these, microRNAs might have indispensible regulatory effects on lncRNAs, based on recent discoveries.
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Tissue-specific insulin signaling in the regulation of metabolism and aging.
IUBMB Life
PUBLISHED: 05-31-2014
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In mammals, insulin signaling regulates glucose homeostasis and plays an essential role in metabolism, organ growth, development, fertility, and lifespan. The defects in this signaling pathway contribute to various metabolic diseases such as type 2 diabetes, polycystic ovarian disease, hypertension, hyperlipidemia, and atherosclerosis. However, reducing the insulin signaling pathway has been found to increase longevity and delay the aging-associated diseases in various animals, ranging from nematodes to mice. These seemly paradoxical findings raise an interesting question as to how modulation of the insulin signaling pathway could be an effective approach to improve metabolism and aging. In this review, we summarize current understanding on tissue-specific functions of insulin signaling in the regulation of metabolism and lifespan. We also discuss the potential benefits and limitations in modulating tissue-specific insulin signaling pathway to improve metabolism and healthspan.
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Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucose-induced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy.
Diabetes
PUBLISHED: 05-21-2014
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Hyperglycemia-induced inflammation and apoptosis have important roles in the pathogenesis of diabetic cardiomyopathy. We recently found that a novel curcumin derivative, C66, is able to reduce the high glucose (HG)-induced inflammatory response. This study was designed to investigate the protective effects on diabetic cardiomyopathy and its underlying mechanisms. Pretreatment with C66 significantly reduced HG-induced overexpression of inflammatory cytokines via inactivation of nuclear factor-?B in both H9c2 cells and neonatal cardiomyocytes. Furthermore, we showed that the inhibition of Jun NH2-terminal kinase (JNK) phosphorylation contributed to the protection of C66 from inflammation and cell apoptosis, which was validated by the use of SP600125 and dominant-negative JNK. The molecular docking and kinase activity assay confirmed direct binding of C66 to and inhibition of JNK. In mice with type 1 diabetes, the administration of C66 or SP600125 at 5 mg/kg significantly decreased the levels of plasma and cardiac tumor necrosis factor-?, accompanied by decreasing cardiac apoptosis, and, finally, improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. Thus, this work demonstrated the therapeutic potential of the JNK-targeting compound C66 for the treatment of diabetic cardiomyopathy. Importantly, we indicated a critical role of JNK in diabetic heart injury, and suggested that JNK inhibition may be a feasible strategy for treating diabetic cardiomyopathy.
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The role of miR-124 in modulating hippocampal neurotoxicity induced by ketamine anesthesia.
Int. J. Neurosci.
PUBLISHED: 05-15-2014
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Purpose: Ketamine is widely used in pediatric anesthesia. Recent studies have demonstrated that excessive application of ketamine leads to cortical neurodegeneration in neonatal brains. The present study aims to characterize the functional role of neuronal microRNA, miR-124, in regulating ketamine-induced neurotoxicity in mouse hippocampus. Methods: Real-time quantitative PCR (RT-PCR) was used to examine the effect of high-dosage ketamine on the expression of miR-124 in murine hippocampus in vitro. Downregulation of hippocampal miR-124 was achieved by lentivirual transfection, and its effects on protecting ketamine-induced hippocampal neurodegeneration were examined both in vitro and in vivo. Results: Hippocampal miR-124 was upregulated by ketamine treatment. Knocking down miR-124 in vitro reduced ketamine-induced apoptosis in hippocampal CA1 neurons, upregulated AMPA receptors phosphorylation and activated the protein kinase C/extracellular signal-regulated kinases (PKC/ERK) pathway. In the in vivo Morris water maze test, following ketamine-induced hippocampal neurodegeneration, mice subjected to hippocampal miR-124 inhibition showed improved memory performance. Conclusions: Our study demonstrated that miR-124 played an important role in regulating ketamine-induced hippocampal neurodegeneration. Inhibiting miR-124 may provide a molecular target to improve memory performance in both human and animals suffering from overanesthetizing-related neurotoxicity.
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The influence of scaffold microstructure on chondrogenic differentiation of mesenchymal stem cells.
Biomed Mater
PUBLISHED: 05-12-2014
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Different forms of biomaterials, including microspheres, sponges, hydrogels and nanofibres have been broadly used in cartilage regeneration; however, effects of internal structures of biomaterials on chondrogenesis of mesenchymal stem cells (MSCs) remain largely unexplored. Here we investigated the effect of physical microenvironments of sponges and hydrogels on chondrogenic differentiation of MSCs. MSCs, cultured in these two scaffold systems, were induced with TGF-?3 in chondrogeneic differentiation medium and the chondrogenic differentiation was evaluated and compared after three weeks. MSCs in the sponges clustered with spindle morphologies, while they distributed homogenously with round morphologies in the hydrogel. The MSCs proliferated faster in the sponge compared to that in the hydrogel. Significantly higher glycosaminoglycan and collagen II were found in the sponges but not in the hydrogels. The different tissue formation ability of MSCs in these two systems could be attributed to the different metabolic requirements and the cellular events prerequisite in the chondrogenic process of MSCs. It is reasonable to conclude that sponges with relatively active microenvironments that facilitate cell-cell contacts and cell-matrix interaction are optimal for early stage of chondrogeneic differentiation.
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Low temperature chemical reduction of fusional sodium metasilicate nonahydrate into a honeycomb porous silicon nanostructure.
Chem. Commun. (Camb.)
PUBLISHED: 05-10-2014
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Honeycomb porous silicon (hp-Si) has been synthesized by a low temperature (200 °C) magnesiothermic reduction of Na2SiO3·9H2O. This process can be regarded as a general synthesis method for other silicide materials. Significantly, hp-Si features excellent electrochemical properties after graphene coating.
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The carboxyl-terminal tail of Noxa protein regulates the stability of Noxa and Mcl-1.
J. Biol. Chem.
PUBLISHED: 05-08-2014
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The BH3-only protein Noxa is a critical mediator of apoptosis and functions primarily by sequestering/inactivating the antiapoptotic Bcl-2 family protein Mcl-1. Although Noxa is a highly labile protein, recent studies suggested that it is degraded by the proteasome in a ubiquitylation-independent manner. In the present study, we investigated the mechanism of Noxa degradation and its ability to regulate the stability of Mcl-1. We found that the ubiquitylation-independent degradation of Noxa does not require a physical association with Mcl-1. A short stretch of amino acid residues in the C-terminal tail was found to mediate the proteasome-dependent degradation of Noxa. Ectopic placement of this degron was able to render other proteins unstable. Surprisingly, mutation of this sequence not only attenuated the rapid degradation of Noxa, but also stabilized endogenous Mcl-1 through the BH3-mediated direct interaction. Together, these results suggest that the C-terminal tail of Noxa regulates the stability of both Noxa and Mcl-1.
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[Lingual thyroglossal duct cyst treatment by low temperature coblation on endoscope].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 05-08-2014
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To investigate the treatment for lingual thyroglossal duct cyst by low temperature cobla tion on endoscope.
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Block the function of nonmuscle myosin II by blebbistatin induces zebrafish embryo cardia bifida.
In Vitro Cell. Dev. Biol. Anim.
PUBLISHED: 05-04-2014
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Nonmuscle myosin II (NM II) is the name given to the multi-subunit protein product of three genes encoding different nonmuscle myosin heavy chains including NM II-A, NM II-B, and NM II-C. Blebbistatin is a small molecule that has been shown to be a relatively specific inhibitor of NM II. Blocking the function of NM II by blebbistatin induces zebrafish embryo cardia bifida at a dose-dependent manner. In situ hybridization analysis with ventricular marker ventricular myosin heavy chain (vmhc) and atrial marker atrial myosin heavy chain (amhc) showed each of the heart contained both distinct atria and ventricle. However, the cardia bifida embryos had highly variable distance between two separate ventricles. We also provided evidence that time window from 12 to 20 h post fertilization (hpf) is necessary and sufficient for cardia bifida formation caused by blebbistatin treatment. Expression of spinster homolog 2 (spns2) was decreased in blebbistatin-treated embryos, suggesting the cardia bifida phenotype caused by NM II inhibition was relevant to precardiac mesoderm migration defects. Through in situ hybridization analysis, we showed that foxa1 was expressed in endoderm of blebbistatin-treated embryos at 24-hpf stage, suggesting the endoderm formation is normal in cardia bifida embryos caused by blebbistatin treatment. In addition, we demonstrated that blebbistatin treatment resulted in morphology alteration of zebrafish cardiomyocytes in vivo and neonatal mouse cardiomyocytes in vitro.
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Label-free selective SERS detection of PCB-77 based on DNA aptamer modified SiO?@Au core/shell nanoparticles.
Analyst
PUBLISHED: 04-29-2014
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A label-free approach to selective detection of 3,3',4,4'-tetrachlorobiphenyl (PCB77) using aptamer modified silica-Au/core-shell nanoparticles (denoted as SiO2@Au core/shell NPs) through surface enhanced Raman scattering (SERS) spectroscopy was proposed. The devised system consisted of SiO2@Au core/shell NPs fixed on the amino-silane functionalized glass slides with the PCB77-binding aptamers attached covalently to the gold surfaces through a thiol linker. The aptamers made of single-stranded DNA (ssDNA) oligomers with one end standing on the Au surface changed the conformation upon conjugation with PCB77, which correspondingly caused the spectral response of the ssDNA oligomers. The intensity ratio I(660 cm(-1))/I(736 cm(-1)) decreased with the amount of PCB77 added, which thus allowed us to measure trace amounts of PCB77 in a selective and quantitative way. This work therefore demonstrates that the design of aptamer-modified SiO2@Au core/shell NPs can be utilized for label-free SERS detection of persistent organic pollutants (POPs) in the environment.
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Photosynthetic changes of flag leaves during senescence stage in super high-yield hybrid rice LYPJ grown in field condition.
Plant Physiol. Biochem.
PUBLISHED: 04-11-2014
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Photosynthetic activities and thylakoid membrane protein patterns as well as the ultrastructure of chloroplasts in flag leaves were investigated during the senescence processes in high-yield hybrid rice LYPJ under field condition. The earlier decrease of PS I activity than PS II in LYPJ was primarily due to the significant degradation of PS I chlorophyll-protein complex. The degradation rate for each chlorophyll-protein complex was different and the order for the stability of thylakoid membrane complexes during flag leaf senescence in rice LYPJ was: LHCII > OEC > PSII core antenna > PSII core > PSI core > LHCI, which was partly supported by the BN-PAGE gel combined with immunoblot analysis. A decrease in the chlorophyll a/b ratio at the senescence stage was observed to coincide with stability of the LHCII subunits. Ultrastructural investigations revealed that the chloroplasts have large loosen stacking grana without interconnecting stroma thylakoids during the senescence processes. It was hypothesized that the stability of grana thylakoids harboring the major LHCII under high radiation condition in summer might played a key role in the dissipation of excess light energy. This alternative strategy would protect photosynthetic apparatus from photodamage and might be causally related to the high yield of this rice cultivar.
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[Association of SOCS3 gene polymorphisms with insulin resistance in Xinjiang Uygur population].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 04-09-2014
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To assess the association of suppressor of cytokine signaling 3 (SOCS3) gene polymorphisms with insulin resistance (IR) in Xinjiang Uygur population.
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Engineering self-sufficient aldehyde deformylating oxygenases fused to alternative electron transfer systems for efficient conversion of aldehydes into alkanes.
Chem. Commun. (Camb.)
PUBLISHED: 03-19-2014
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Self-sufficient aldehyde deformylating oxygenases (ADOs) from Synechococcus elongatus PCC7942 fused to alternative electron transfer systems were successfully designed, constructed, characterized and used for efficient conversion of aldehydes into alkanes for the first time.
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The complete mitochondrial genome of the Parastromateus niger (Perciformes, Carangidae).
Mitochondrial DNA
PUBLISHED: 03-13-2014
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Abstract In this study, we have sequenced the complete mitochondrial genome of the Parastromateus niger. The mitochondrial genome is 16,561?bp long and contains 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a control region. The gene order and composition of Parastromateus niger mitochondrial genome is similar to that of most other vertebrates. The nucleotide compositions of the light strand are 28.23% of A, 29.51% of C, 26.01% of T and 16.16% of G. With the exception of five tRNA genes, all other mitochondrial genes are encoded on the heavy strand.
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Rapid, in situ detection of cocaine residues based on paper spray ionization coupled with ion mobility spectrometry.
Analyst
PUBLISHED: 02-25-2014
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In this paper, a novel approach based on paper spray ionization coupled with ion mobility spectrometry (PSI-IMS) was developed for rapid, in situ detection of cocaine residues in liquid samples and on various surfaces (e.g. glass, marble, skin, wood, fingernails), without tedious sample pretreatment. The obvious advantages of PSI are its low cost, easy operation and simple configuration without using nebulizing gas or discharge gas. Compared with mass spectrometry, ion mobility spectrometry (IMS) takes advantage of its low cost, easy operation, and simple configuration without requiring a vacuum system. Therefore, IMS is a more congruous detection method for PSI in the case of rapid, in situ analysis. For the analysis of cocaine residues in liquid samples, dynamic responses from 5 ?g mL(-1) to 200 ?g mL(-1) with a linear coefficient (R(2)) of 0.992 were obtained. In this case, the limit of detection (LOD) was calculated to be 2 ?g mL(-1) as signal to noise (S/N) was 3 with a relative standard deviation (RSD) of 6.5% for 11 measurements (n = 11). Cocaine residues on various surfaces such as metal, glass, marble, wood, skin, and fingernails were also directly analyzed before wiping the surfaces with a piece of paper. The LOD was calculated to be as low as 5 ng (S/N = 3, RSD = 6.3%, n = 11). This demonstrates the capability of the PSI-IMS method for direct detection of cocaine residues at scenes of cocaine administration. Our results show that PSI-IMS is a simple, sensitive, rapid and economical method for in situ detection of this illicit drug, which could help governments to combat drug abuse.
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The effects of CES1A2 A(-816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease.
Pharmacogenet. Genomics
PUBLISHED: 02-19-2014
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Carboxylesterase 1 hydrolyzes the majority of clopidogrel to the inactive metabolite. The aim of this study was to assess the effects of the CES1A2 A(-816)C polymorphism and other genetic and clinical factors on clopidogrel response variability. An additional aim was to investigate the relationship between genetic variations and development of stent thrombosis (ST).
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Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-?B and MAPK signaling inactivation.
Int. Immunopharmacol.
PUBLISHED: 02-18-2014
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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal (GI) tract, and currently no curative treatment is available. Mangiferin, a natural glucosylxanthone mainly from the fruit, leaves and stem bark of a mango tree, has a strong anti-inflammatory activity. We sought to investigate whether mangiferin attenuates inflammation in a mouse model of chemically induced IBD. Pre-administration of mangiferin significantly attenuated dextran sulfate sodium (DSS)-induced body weight loss, diarrhea, colon shortening and histological injury, which correlated with the decline in the activity of myeloperoxidase (MPO) and the level of tumor necrosis factor-? (TNF-?) in the colon. DSS-induced degradation of inhibitory ?B? (I?B?) and the phosphorylation of nuclear factor-kappa B (NF-?B) p65 as well as the mRNA expression of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-?, interleukin-1? (IL-1?) and IL-6) in the colon were also downregulated by mangiferin treatment. Additionally, the phosphorylation/activation of DSS-induced mitogen-activated protein kinase (MAPK) proteins was also inhibited by mangiferin treatment. In accordance with the in vivo results, mangiferin exposure blocked TNF-?-stimulated nuclear translocation of NF-?B in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-?-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-?B transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-?B and MAPK signaling inhibition. Since mangiferin is a natural compound with little toxicity, the results may contribute to the effective utilization of mangiferin in the treatment of human IBD.
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Toward therapeutic effects evaluation of chronic myeloid leukemia drug: electrochemical platform for caspase-3 activity sensing.
Biosens Bioelectron
PUBLISHED: 02-18-2014
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In recent decades, advanced therapies and novel scientific drug evaluation systems for chronic myeloid leukemia (CML) treatment are very urgent due to its increasing morbidity. The combination of dasatinib with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was supposed to be effective for leukemia therapy. Taking full advantage of novel nano-biotechnology, we have developed a robust electrochemical cytosensing approach to profile the therapeutic effects of dasatinib and TRAIL by probing the activity of caspase-3 from apoptotic CML cells. The sensor was on a base of a glassy carbon electrode (GCE) modified with nano-materials composed of Au nanoparticles (AuNPs), poly(dimethyl diallyl ammonium chloride) (PDDA), and carbon nanotubes (CNTs). Then the platform immobilized the biotinylated DEVD-peptide (biotin-Gly-Asp-Gly-Asp-Glu-Val-Asp-Gly-Cys) via the strong bonding between AuNPs and the thiol group (Au-S bond). In particular, the sensor was then constructed with the environmentally friendly alkaline phosphatase (ALP) via the specific interaction between the biotin and streptavidin, and could retest detection indirectly for caspase-3 sensing by detecting the differential pulse voltammetry (DPV) signal of enzymatic catalysis product, ascorbic acid (AA). The results indicated that either dasatinib or TRAIL could successfully induce the apoptosis of CML cells, while the combination of dasatinib and TRAIL resulted in an improved therapeutic effect, suggesting a novel optimized strategy for CML therapy. This novel electrochemical sensing strategy exhibits attractive advantages of environmental benignity, simple performance, high stability, and may be readily expanded to evaluate other cancer therapeutic effects.
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Upregulation of the splice variant MUC4/Y in the pancreatic cancer cell line MIA PaCa-2 potentiates proliferation and suppresses apoptosis: new insight into the presence of the transcript variant of MUC4.
Oncol. Rep.
PUBLISHED: 02-14-2014
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MUC4/Y, the transcript variant 4 of MUC4, lacks exon 2 as compared with the transcript variant 1 of MUC4. To date, direct evidence for the function of MU4/Y remains to be reported. Previous studies based their hypotheses regarding the function of MUC4/Y on the characteristic structure domains of this variant. The aim of the present study was to investigate the specific function of MUC4/Y. The pancreatic cancer cell line MIA PaCa-2 with low MUC4/Y expression was used to establish a stable cell model of MUC4/Y upregulation using a lentivirus vector system. Results showed that MUC4/Y anchored on the cytomembrane and affected cell morphology and cell cycle. Functional analyses indicated that MUC4/Y upregulation slightly potentiated cell proliferation and significantly suppressed apoptosis both in vivo and in vitro. Further studies revealed that the JNK and AKT signalling pathways were activated. Meanwhile, MUC4/Y upregulation elicited minimal effect on the phosphorylation level of HER2, a membrane partner of MUC4. These results suggest that MUC4/Y promotes tumour progression through its anti-apoptotic and weak mitogenic effect on MIA PaCa-2 cells.
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Combining electronic and steric effects for highly stable unsymmetric pentacenes.
Chemistry
PUBLISHED: 02-12-2014
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This paper describes the reactivity of unsymmetrically substituted pentacenes to photochemical oxidation. Acenes in general, and pentacenes in particular, are a key family of compounds for a variety of organic electronics applications. The instability of many pentacene derivatives, particularly to oxidation, is an important restriction in their applicability. Several substitution strategies for decreasing the reactivity of pentacene exist, but these almost always involve symmetrically substituted derivatives, restricting the chemical space of structures from which to choose. In this paper, we demonstrate that combining electronic and steric effects yields highly stable unsymmetrically substituted pentacenes.
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Clinical features and gene mutational spectrum of CDKL5-related diseases in a cohort of Chinese patients.
BMC Med. Genet.
PUBLISHED: 02-12-2014
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Mutations in the cyclin-dependent kinase-like 5 (CDKL5) (NM_003159.2) gene have been associated with early-onset epileptic encephalopathies or Hanefeld variants of RTT(Rett syndrome). In order to clarify the CDKL5 genotype-phenotype correlations in Chinese patients, CDKL5 mutational screening in cases with early-onset epileptic encephalopathies and RTT without MECP2 mutation were performed.
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[Application of multiplex ligation-dependent probe amplification for rapid detection of aneuploidies and structural chromosomal abnormalities in prenatal diagnosis].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 02-11-2014
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To explore the value of multiplex ligation-dependent probe amplification (MLPA) for rapid detection of aneuploidies and structural chromosomal abnormalities during prenatal diagnosis.
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[Genetic features and mechanism of Rett syndrome in Chinese population].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 02-11-2014
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To analyze the genetic characteristics and molecular mechanism of Chinese patients with Rett syndrome (RTT) and assess the recurrent risk in order to provide genetic counseling for the family with RTT patient.
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Cross-linkage effect of cellulose/laponite hybrids in aqueous dispersions and solid films.
Carbohydr Polym
PUBLISHED: 02-11-2014
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Homogenous cellulose/laponite aqueous dispersions and composite films were respectively prepared from the pre-cooling NaOH/urea aqueous systems. Rheological measurements of aqueous dispersions demonstrated a sol-to-gel transition triggered by loading of laponite, reflecting a cross-linkage effect of cellulose/laponite hybrids. Similarly, based on scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) characterizations, as well as mechanical and thermal measurements, the cross-linkage effect of cellulose/laponite hybrids was also found in solid films, which played an important role in improving the tensile strength (?b) of composite films. For instance, the ?b exhibited a largest enhancement up to 75.7% at a critical laponite content of 0.100 wt%, indicating that the property of composite film was closely related with the dispersion and interaction state of laponite, i.e. its content in cellulose matrix. These results were expected to provide significant information for fabrication and utility of cellulose-based materials.
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Determination of picogram quantities of chlortoluron in soil samples by luminol-chitosan chemiluminescence system.
Environ Sci Pollut Res Int
PUBLISHED: 02-10-2014
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Based on the enhancing effect of chitosan (CS) on luminol-dissolved oxygen chemiluminescence (CL) reaction, a flow injection (FI) luminol-CS CL system was established. It was found that the increase of CL intensity was proportional to the concentrations of CS ranging from 0.7 to 10.0 ?mol l(-1). In the presence of chlortoluron (CTU), the CL intensity of luminol-CS system could be obviously inhibited and the decrements of CL intensity were linearly proportional to the logarithm of CTU concentrations ranging from 0.01 to 70.0 ng ml(-1), giving the limit of detection 3.0 pg ml(-1) (3?). At a flow rate of 2.0 ml min(-1), the whole process including sampling and washing could be accomplished within 36 s, offering a sample throughput of 100 h(-1). The proposed FI-CL method was successfully applied to the determination of CTU in soil samples with recoveries ranging from 95.0 % to 105.3 % and the relative standard deviations (RSDs) of less than 4.0 %.
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Characterizing IgG4-related disease with ¹?F-FDG PET/CT: a prospective cohort study.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 02-07-2014
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IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD.
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Genome-wide detection of selective signatures in Simmental cattle.
J. Appl. Genet.
PUBLISHED: 02-04-2014
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Artificial selection has greatly improved the beef production performance and changed its genetic basis. High-density SNP markers provide a way to track these changes and use selective signatures to search for the genes associated with artificial selection. In this study, we performed extended haplotype homozygosity (EHH) tests based on Illumina BovineSNP50 (54 K) Chip data from 942 Simmental cattle to identify significant core regions containing selective signatures, then verified the biological significance of these identified regions based on some commonly used bioinformatics analyses. A total of 224 regions over the whole genome in Simmental cattle showing the highest significance and containing some important functional genes, such as GHSR, TG and CANCNA2D1 were chosen. We also observed some significant terms in the enrichment analyses of second GO terms and KEGG pathways, indicating that these genes are associated with economically relevant cattle traits. This is the first detection of selection signature in Simmental cattle. Our findings significantly expand the selection signature map of the cattle genome, and identify functional candidate genes under positive selection for future genetic research.
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Haplotype-based approach for noninvasive prenatal diagnosis of congenital adrenal hyperplasia by maternal plasma DNA sequencing.
Gene
PUBLISHED: 02-02-2014
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Prenatal diagnosis of congenital adrenal hyperplasia (CAH) is of clinical significance because in utero treatment is available to prevent virilization of an affected female fetus. However, traditional prenatal diagnosis of CAH relies on genetic testing of fetal genomic DNA obtained using amniocentesis or chorionic villus sampling, which is associated with an increased risk of miscarriage. The aim of this study was to demonstrate the feasibility of a new haplotype-based approach for the noninvasive prenatal testing of CAH due to 21-hydroxylase deficiency. Parental haplotypes were constructed using target-region sequencing data of the parents and the proband. With the assistance of the parental haplotypes, we recovered fetal haplotypes using a hidden Markov model (HMM) through maternal plasma DNA sequencing. In the genomic region around the CYP21A2 gene, the fetus inherited the paternal haplotype '0' alleles linked to the mutant CYP21A2 gene, but the maternal haplotype '1' alleles linked to the wild-type gene. The fetus was predicted to be an unaffected carrier of CAH, which was confirmed by genetic analysis of fetal genomic DNA from amniotic fluid cells. This method was further validated by comparing the inferred SNP genotypes with the direct sequencing data of fetal genomic DNA. The result showed an accuracy of 96.41% for the inferred maternal alleles and an accuracy of 97.81% for the inferred paternal alleles. The haplotype-based approach is feasible for noninvasive prenatal testing of CAH.
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Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway.
J. Nutr. Biochem.
PUBLISHED: 01-22-2014
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Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (ulcerative colitis like and Crohn's disease like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated inflammation through inhibiting the activity of myeloperoxidase, the levels of TNF-? and IL-6, the mRNA expression of proinflammatory mediators (iNOS, ICAM-1, COX2, TNF-?, IL-2 and IL-6) and the phosphorylation of I?B? and NF-?B p65. PXR gene overexpression inhibited NF-?B luciferase activity, and the inhibition was potentiated by isorhamnetin treatment. PXR knockdown by siRNA demonstrated the necessity for PXR in isorhamnetin-mediated up-regulation of xenobiotic metabolism genes. Ligand pocket-filling mutants (S247W/C284W and S247W/C284W/S208W) of human PXR weakened the effect of isorhamnetin on PXR activation. Molecular docking studies and time-resolved fluorescence resonance energy transfer competitive binding assays confirmed the ligand (isorhamnetin)-binding affinity. These results clearly demonstrated the ameliorating effect of isorhamnetin on experimental IBD via PXR-mediated up-regulation of xenobiotic metabolism and down-regulation of NF-?B signaling. The novel findings may contribute to the effective utilization of isorhamnetin or its derivatives as a PXR ligand in the treatment of human IBD.
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Differences in the knowledge and compliance with secondary prevention of stroke between transient ischaemic attack patients with and without subsequent stroke.
J Clin Nurs
PUBLISHED: 01-21-2014
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To evaluate the differences in the knowledge and compliance with secondary prevention of stroke between transient ischaemic attack patients with and without subsequent stroke.
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Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy.
Endocrine
PUBLISHED: 01-18-2014
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This study aimed to compare the efficacy and safety of prostaglandin E1 plus methylcobalamin (PGE1-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN). We searched published randomized controlled trials (RCTs) of PGE1 combined with MC for DPN up to June 1, 2013. Data were extracted to evaluate methodological quality and describe characteristics of studies in duplicate. A random or a fixed effect model was used to analyze outcomes which were expressed as relative risk (RR) or mean difference with a 95 % confidence interval (CI). All data were analyzed using Review Manager 5.2 software. Twenty-six RCTs involving 2,107 individuals were included. Meta-analysis showed that PGE1-MC combination therapy was significantly better than MC monotherapy (RR = 1.40; 95 % CI 1.33-1.48) on efficacy. The weighted mean differences in nerve conduction velocities (NCVs) were 6.72 (95 % CI: 5.42-8.02) for median motor nerve conduction velocity (MNCV), 5.13 (CI 4.13-6.13) for median sensory nerve conduction velocity (SNCV), 5.74 (CI 4.87-6.61) for peroneal MNCV and 4.62 (CI 3.89-5.34) for peroneal SNCV in favor of the PGE1 + MC combination group. Moreover, there were no serious adverse events in both groups during the treatment period. The results of the meta-analysis show that treatment with PGE1-MC is safe and can gain better outcomes in neuropathic symptoms and NCVs compared with MC alone. However, the conclusion may not be strong because most of the studies included in this meta-analysis have poor methodological quality.
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Molecular analysis of the CYP21A2 gene in Chinese patients with steroid 21-hydroxylase deficiency.
Clin. Biochem.
PUBLISHED: 01-16-2014
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21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), a family of autosomal recessive disorders involving impaired cortisol synthesis. This study aimed to design a reliable and rational approach for identifying mutations in the CYP21A2 gene and to characterize the molecular basis of 21-OHD in 30 Chinese patients.
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Association of glucose transporter 4 genetic polymorphisms with obstructive sleep apnea syndrome in Han Chinese general population: a cross-section study.
Lipids Health Dis
PUBLISHED: 01-07-2014
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Obstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome. A growing number of studies have shown OSAS is an independent factor for insulin resistance, glucose intolerance and type2 diabetes. However, relationship of OSAS with dysglycemia is complex and still remains poorly understood. Glucose transporter 4 (GLUT4) gene is Human and rodents' main glucose transporter sensitive to insulin, and therefore confirmation of candidate gene polymorphisms and association with OSAS is needed. Aim of our study was to assess whether GLUT4 gene polymorphisms are associated with OSAS.
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Transcription factor Ets1 regulates expression of thioredoxin-interacting protein and inhibits insulin secretion in pancreatic ?-cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Long-term activation of extracellular-regulated kinase (ERK1/2) pathway has been shown to cause glucotoxicity and inhibit insulin gene expression in ?-cells. Transcription factor Ets1 is activated by ERK1/2-mediated phosphorylation at the Thr38 residue. We hypothesize that Ets1 plays an important role in mediating ERK1/2 induced glucotoxicity in ?-cells. We determined the role of Ets1 in Min6 cells and isolated mouse islets using overexpression and siRNA mediated knockdown of Ets1. The results show that Ets1 was localized in insulin-staining positive cells but not in glucagon-staining positive cells. Overexpression of Ets1 reduced glucose-stimulated insulin secretion in primary mouse islets. Overexpression of Ets1 in Min6 ?-cells and mouse islets increased expression of thioredoxin-interacting protein (TXNIP). Conversely, knockdown of Ets1 by siRNA reduced expression of TXNIP in Min6 cells. Ets1 was associated with the txnip promoter in min6 cells and transfection of 293 cells with Ets1 and p300 synergistically increased txnip promoter reporter activity. Moreover, overexpression of Ets1 inhibited Min6 cell proliferation. Our results suggest that Ets1, by promoting TXNIP expression, negatively regulates ?-cell function. Thus, over-activation of Ets1 may contribute to diet-induced ?-cell dysfunction.
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The cytoplasmic tail of FPC antagonizes the full-length protein in the regulation of mTOR pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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FPC (fibrocystin or polyductin) is a single transmembrane receptor-like protein, responsible for the human autosomal recessive polycystic kidney disease (ARPKD). It was recently proposed that FPC undergoes a Notch-like cleavage and subsequently the cleaved carboxy(C)-terminal fragment translocates to the nucleus. To study the functions of the isolated C-tail, we expressed the intracellular domain of human FPC (hICD) in renal epithelial cells. By 3-dimensional (3D) tubulogenesis assay, we found that in contrast to tubule-like structures formed from control cells, hICD-expressing cells exclusively formed cyst-like structures. By western blotting, we showed that the Akt/mTOR pathway, indicated by increased phosphorylation of Akt at serine 473 and S6 kinase 1 at threonine 389, was constitutively activated in hICD-expressing cells, similar to that in FPC knockdown cells and ARPKD kidneys. Moreover, application of mTOR inhibitor rapamycin reduced the size of the cyst-like structures formed by hICD-expressing cells. Application of either LY294002 or wortmannin inhibited the activation of both S6K1 and Akt. Expression of full-length FPC inhibited the activation of S6 and S6 kinase whereas co-expression of hICD with full-length FPC antagonized the inhibitory effect of full-length FPC on mTOR. Taken together, we propose that FPC modulates the PI3K/Akt/mTOR pathway and the cleaved C-tail regulates the function of the full-length protein.
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VE-statin/Egfl7 siRNA inhibits angiogenesis in malignant glioma in vitro.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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This study investigated the role of VE-statin/Egfl7 and its mechanism in angiogenesis in malignant glioma. Transwell culture plates were used to establish an U251-HUVEC co-culture system, which was used to mimic the interaction between malignant glioma and endothelial cells. Lentiviral vectors expressing VE-statin/Egfl7 siRNA were constructed, and U251 cells and HUVECs were transfected to inhibit VE-statin/Egfl7 expression. The proliferation, adherence, migration, and lumen formation of endothelial cells were assayed to investigate the influence of VE-statin/Egfl7 on angiogenesis in malignant glioma in vitro. Data showed that HUVEC growth was temporarily slowed after silencing the VE-statin/Egfl7 gene but rapidly returned to normal. Although endothelial cell migration was not influenced, cell adherence was markedly inhibited. Furthermore, the endothelial cells failed to generate a capillary-like lumen after VE-statin/Egfl7 gene silencing. Therefore, it can be concluded that VE-statin/Egfl7 may regulate the adherence of endothelial cells, thus playing an important role in endothelium-induced lumen formation during angiogenesis in malignant glioma.
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Metformin plays a dual role in MIN6 pancreatic ? cell function through AMPK-dependent autophagy.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2014
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Metformin improves insulin sensitivity in insulin sensitive tissues such as liver, muscle and fat. However, the functional roles and the underlying mechanism of metformin action in pancreatic ? cells remain elusive. Here we show that, under normal growth condition, metformin suppresses MIN6 ? cell proliferation and promotes apoptosis via an AMPK-dependent and autophagy-mediated mechanism. On the other hand, metformin protects MIN6 cells against palmitic acid (PA)-induced apoptosis. Our findings indicate that metformin plays a dual role in ? cell survival and overdose of this anti-diabetic drug itself may lead to potential ? cell toxicity.
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An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.
PLoS ONE
PUBLISHED: 01-01-2014
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The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue.
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Effective functional maturation of invariant natural killer T cells is constrained by negative selection and T-cell antigen receptor affinity.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-16-2013
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The self-reactivity of their T-cell antigen receptor (TCR) is thought to contribute to the development of immune regulatory cells, such as invariant NK T cells (iNKT). In the mouse, iNKT cells express TCRs composed of a unique V?14-J?18 rearrangement and recognize lipid antigens presented by CD1d molecules. We created mice expressing a transgenic TCR-? chain that confers high affinity for self-lipid/CD1d complexes when randomly paired with the mouse iNKT V?14-J?18 rearrangement to study their development. We show that although iNKT cells undergo agonist selection, their development is also shaped by negative selection in vivo. In addition, iNKT cells that avoid negative selection in these mice express natural sequence variants of the canonical TCR-? and decreased affinity for self/CD1d. However, limiting the affinity of the iNKT TCRs for "self" leads to inefficient Egr2 induction, poor expression of the iNKT lineage-specific zinc-finger transcription factor PLZF, inadequate proliferation of iNKT cell precursors, defects in trafficking, and impaired effector functions. Thus, proper development of fully functional iNKT cells is constrained by a limited range of TCR affinity that plays a key role in triggering the iNKT cell-differentiation pathway. These results provide a direct link between the affinity of the TCR expressed by T-cell precursors for self-antigens and the proper development of a unique population of lymphocytes essential to immune responses.
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Thymic Medullary Epithelium and Thymocyte Self-Tolerance Require Cooperation between CD28-CD80/86 and CD40-CD40L Costimulatory Pathways.
J. Immunol.
PUBLISHED: 12-13-2013
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A critical process during thymic development of the T cell repertoire is the induction of self-tolerance. Tolerance in developing T cells is highly dependent on medullary thymic epithelial cells (mTEC), and mTEC development in turn requires signals from mature single-positive thymocytes, a bidirectional relationship termed thymus crosstalk. We show that CD28-CD80/86 and CD40-CD40L costimulatory interactions, which mediate negative selection and self-tolerance, upregulate expression of LT?, LT?, and receptor activator for NF-?B in the thymus and are necessary for medullary development. Combined absence of CD28-CD80/86 and CD40-CD40L results in profound deficiency in mTEC development comparable to that observed in the absence of single-positive thymocytes. This requirement for costimulatory signaling is maintained even in a TCR transgenic model of high-affinity TCR-ligand interactions. CD4 thymocytes maturing in the altered thymic epithelial environment of CD40/CD80/86 knockout mice are highly autoreactive in vitro and are lethal in congenic adoptive transfer in vivo, demonstrating a critical role for these costimulatory pathways in self-tolerance as well as thymic epithelial development. These findings demonstrate that cooperativity between CD28-CD80/86 and CD40-CD40L pathways is required for normal medullary epithelium and for maintenance of self-tolerance in thymocyte development.
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TRAF3 enforces the requirement for T cell cross-talk in thymic medullary epithelial development.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-09-2013
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Induction of self-tolerance in developing T cells depends on medullary thymic epithelial cells (mTECs), whose development, in turn, requires signals from single-positive (SP) thymocytes. Thus, the absence of SP thymocytes in Tcra(-/-) mice results in a profound deficiency in mTECs. Here, we have probed the mechanism that underlies this requirement for cross-talk with thymocytes in medullary development. Previous studies have implicated nonclassical NF-?B as a pathway important in the development of mTECs, because mice lacking RelB, NIK, or IKK?, critical components of this pathway, have an almost complete absence of mTECs, with resulting autoimmune pathology. We therefore assessed the effect of selective deletion in TEC of TNF receptor-associated factor 3 (TRAF3), an inhibitor of nonclassical NF-?B signaling. Deletion of TRAF3 in thymic epithelial cells allowed RelB-dependent development of normal numbers of AIRE-expressing mTECs in the complete absence of SP thymocytes. Thus, mTEC development can occur in the absence of cross-talk with SP thymocytes, and signals provided by SP T cells are needed to overcome TRAF3-imposed arrest in mTEC development mediated by inhibition of nonclassical NF-?B. We further observed that TRAF3 deletion is also capable of overcoming all requirements for LT?R and CD40, which are otherwise necessary for mTEC development, but is not sufficient to overcome the requirement for RANKL, indicating a role for RANKL that is distinct from the signals provided by SP thymocytes. We conclude that TRAF3 plays a central role in regulation of mTEC development by imposing requirements for SP T cells and costimulation-mediated cross-talk in generation of the medullary compartment.
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Non-antiepileptic drugs for trigeminal neuralgia.
Cochrane Database Syst Rev
PUBLISHED: 12-04-2013
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Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Standard treatment is with anti-epileptic drugs. Non-antiepileptic drugs have been used in the management of trigeminal neuralgia since the 1970s. This is an update of a review first published in 2006 and previously updated in 2011.
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Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 11-14-2013
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Paeonia lactiflora Pall is one of the most well-known herbs in China, Korea, and Japan for more than 1,200 years. Paeoniflorin, the major bioactive component of peony root, has recently been reported to have anticolitic activity. However, the underlying molecular mechanism is unclear. The present study was to explore the possible mechanism of paeoniflorin in attenuating dextran sulfate sodium (DSS)-induced colitis. Pre- and coadministration of paeoniflorin significantly reduced the severity of colitis and resulted in downregulation of several inflammatory parameters in the colon, including the activity of myeloperoxidase (MPO), the levels of TNF-? and IL-6, and the mRNA expression of proinflammatory mediators (MCP-1, Cox2, IFN-?, TNF-?, IL-6, and IL-17). The decline in the activation of NF-?B p65, ERK, JNK, and p38 MAPK correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) but not TLR2 or TLR5 expression. In accordance with the in vivo results, paeoniflorin downregulated TLR4 expression, blocked nuclear translocation of NF-?B p65, and reduced the production of IL-6 in LPS-stimulated mouse macrophage RAW264.7 cells. Transient transfection assay performed in LPS-stimulated human colon cancer HT-29 cells indicated that paeoniflorin inhibits NF-?B transcriptional activity in a dose-dependent manner. TLR4 knockdown and overexpression experiments demonstrated a requirement for TLR4 in paeoniflorin-mediated downregulation of inflammatory cytokines. Thus, for the first time, the present study indicates that paeoniflorin abrogates DSS-induced colitis via decreasing the expression of TLR4 and suppressing the activation of NF-?B and MAPK pathways.
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MUC4-induced nuclear translocation of ?-catenin: A novel mechanism for growth, metastasis and angiogenesis in pancreatic cancer.
Cancer Lett.
PUBLISHED: 10-09-2013
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The membrane mucin MUC4 is aberrantly expressed in multiple cancers and is of clinical significance to diagnosis and prognosis in pancreatic cancer. However, the role of MUC4 in angiogenesis and the potential association among these malignant capabilities have not been explored. In this study, we investigated the collective signaling mechanisms associated with MUC4-induced growth, metastasis and angiogenesis in pancreatic cancer. Knockdown of MUC4 in two pancreatic cancer cell lines led to downregulation of lysosomal degradation of E-cadherin by Src kinase through downregulation of pFAK and pSrc pathway. The downregulation of lysosomal degradation of E-cadherin in turn induced the formation of E-cadherin/?-catenin complex and membrane translocation of ?-catenin, resulting in the downregulation of Wnt/?-catenin signaling pathway. Thus, the Wnt/?-catenin target genes c-Myc, Cyclin D1, CD44 and VEGF were down-regulated and their malignant functions proliferation, metastasis and angiogenesis were reduced. Taken together, MUC4-induced nuclear translocation of ?-catenin is a novel mechanism for growth, metastasis and angiogenesis of pancreatic cancer.
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hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and migration.
Int. J. Oncol.
PUBLISHED: 09-04-2013
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Expression of the transmembrane-4-L-six-family-1 (TM4SF1) is high in human pancreatic cancer cells, but the underlying mechanism remains unclear. In this study, we aimed to identify and characterize microRNAs that regulate TM4SF1 expression in PC cells. Western blot analysis and quantitative polymerase chain reaction were used to detect TM4SF1 and hsa-miR-141 levels in four PC cell lines. SW1990 and BxPc-3 cells were transfected with the inhibitor miR-141, the inhibitor negative control, the miR-141 mimic and the mimic negative control; and cell invasion, migration, proliferation, cell cycle progression and apoptosis were detected by Transwell, MTT and flow cytometry assays, respectively. The miR-141 levels negatively correlated with the TM4SF1 protein levels in PC cells. The TM4SF1 protein levels were lower in the 141M group but higher in the 141I group, although the TM4SF1 mRNA levels had no significant changes, compared to the negative controls. Luciferase assays demonstrated that hsa-miR-141 directly targeted the 3-untranslated region of the TM4SF1 gene. In addition, miR-141 downregulated TM4SF1 expression to inhibit invasion and migration of PC cells but had no effects on cell proliferation, cell cycle progression or apoptosis. TM4SF1 is a direct target of miR-141. Our findings that TM4SF1 expression was inhibited by miR-141 provide new insights into the oncogenic mechanism of TM4SF1 and suggest that miR-141 represents a novel molecular target for PC therapy.
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[Endoscope assisted coblation surgery for treating subglottic stenosis].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-31-2013
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To introduce a new surgical treatment for subglottic stenosis.
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Leptin in chronic kidney disease: a link between hematopoiesis, bone metabolism, and nutrition.
Int Urol Nephrol
PUBLISHED: 08-23-2013
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Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.
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Association between two functional fibrinogen-related polymorphisms and ischemic stroke: a case-control study.
Genet Test Mol Biomarkers
PUBLISHED: 08-14-2013
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Currently, there is a debate regarding the roles of two functional fibrinogen-related variants (rs6050 and rs1800790) and ischemic stroke (IS).
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[Effect of Pinch-3 gene interference of glomerular podocytes on cell morphology and cell traction force].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-20-2013
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Pinch-3 protein is an important constituent of cell membranes, which directly affects the cell morphology and mechanical properties. We observed and compared the change of morphology and cell traction force of glomerular podocytes before and after Pinch-3 gene inhibition by gene interference technology in this experiment. We found that a number of pores appeared on the cell surface, and the cell projected area were increased at the same time, with an approximate average about an increase of 40% after Pinch-3 gene inhibition. The results showed that the cell traction force of glomerular podocytes was significantly reduced, with an approximate average decrease of 40%, the maximum value of the cell traction force was reduced and the distribution of cell traction force became dispersive. All this suggested that after Pinch-3 gene inhibition, some pores created on the cell surface influenced the physical properties of glomerular podocytes and then affected the cell projected area and influenced the formation and distribution of cell traction force of the glomerular podocytes as well.
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[Development of a wrist wearing and remote heart rate alarm apparatus].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-18-2013
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We have developed a new wrist wearing heart rate monitoring alarm apparatus, which can detect the patients real-time pulse waves. When the abnormal heart rate appears or pulse disappears, the monitoring alarm will sound and dial the remote telephone for help simultaneously. This apparatus uses the switch circuit to control the keyboard of mobile phone, and dials remote telephone in the help of mature technology and communication platform of mobile phones. The intelligent program can distinguish digital pulse signal, pick out the correct cycle of heartbeat intelligently. The new wrist wearing heart rate monitoring alarm apparatus will calculate an average heart rate when it captures consecutively five correct electrocardiograph waveforms. It really provides a simple, inexpensive and effective way for the patients with heart disease.
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Development of an ion mobility spectrometer with a paper spray ionization source.
Rev Sci Instrum
PUBLISHED: 07-05-2013
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Paper spray (PS) ionization is a recently developed ion source that has been used to analyze samples in their native environments at ambient pressure without requiring sample preparation or pre-separation. The design of an ion mobility spectrometer (IMS) coupled with PS ionization can help expand IMS applications to on-site detection of complex liquid samples. We report a paper spray ionization ion mobility spectrometer prototype that consists of a PS source and an ion mobility spectrometer optimized using a numerical simulation. The performance of the design was evaluated by measuring 2, 6-di-tert-butylpyridine (2, 6-DtBP). The mobility spectra of the 2, 6-DtBP exhibited a single-product ion peak with reduced mobility calculated at 1.42 cm(2)?(V s) and a linear response of 0.1-10 ?g?ml, with an estimated detection limit of 0.05 ?g?ml. The Relative Standard Deviation for 1 ?g?ml was 5.7% over 11 measurements. The highest resolving power (47) was measured for 2, 6-DtBP. Based on these preliminary results, the present PSIMS design is expected to become a tool of choice for the rapid analysis of complex liquid samples.
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Cells behave distinctly within sponges and hydrogels due to differences of internal structure.
Tissue Eng Part A
PUBLISHED: 06-08-2013
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Different forms of biomaterials, including microspheres, sponges, hydrogels, and nanofibers, have been broadly used in cartilage regeneration; however, effects of internal structures of the biomaterials on cells and chondrogenesis remain largely unexplored. We hypothesized that different internal structures of sponges and hydrogels led to phenotypic disparity of the cells and may lead to disparate chondrogenesis. In the current study, the chondrocytes in sponges and hydrogels of chitosan were compared with regard to cell distribution, morphology, gene expression, and production of extracellular matrix. The chondrocytes clustered or attached to the materials with spindle morphologies in the sponges, while they distributed evenly with spherical morphologies in the hydrogels. The chondrocytes proliferated faster with elevated gene expression of collagen type I and down-regulated gene expression of aggracan in sponges, when compared with those in the hydrogels. However, there was no significant difference of the expression of collagen type II between these two scaffolds. Excretion of both glycosaminoglycan (GAG) and collagen type II increased with time in vitro, but there was no significant difference between the sponges and the hydrogels. There was no significant difference in secretion of GAG and collagen type II in the two scaffolds, while the levels of collagen type I and collagen type X were much higher in sponges compared with those in hydrogels during an in vivo study. Though the chondrocytes displayed different phenotypes in the sponges and hydrogels, they led to comparable chondrogenesis. An optimized design of the biomaterials could further improve chondrogenesis through enhancing functionalities of the chondrocytes.
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Association between Genetic Variations in MTNR1A and MTNR1B Genes and Gestational Diabetes Mellitus in Han Chinese Women.
Gynecol. Obstet. Invest.
PUBLISHED: 05-27-2013
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Background/Aims: The purpose of this study was to investigate the association between MTNR1A and MTNR1B gene polymorphisms and gestational diabetes mellitus (GDM) in Han Chinese women. Methods: Study participants included 350 patients with GDM and 480 control subjects. Three single-nucleotide polymorphisms (SNPs; rs2119882 in MTNR1A and rs10830963 and rs10830962 in MTNR1B) were genotyped using direct sequencing. Genotype and allele distributions of SNPs in cases of GDM and controls were analyzed. Association of the MTNR1A and MTNR1B gene variants with plasma glucose and insulin levels as well as blood lipid levels was further investigated. Results: The frequencies of genotypes and allele types of rs2119882 in MTNR1A and rs10830963 in MTNR1B were significantly different between women with GDM and controls (p < 0.05). Moreover, in the GDM group, these SNPs were associated with increased fasting plasma glucose concentrations (p < 0.001) and increased homeostasis model assessment of insulin resistance (p < 0.001). The rs10830962 polymorphism in MTNR1B was not associated with an increased risk of developing GDM or any of the clinical or metabolic characteristics in patients with GDM (p > 0.05). Conclusion: The genetic polymorphisms rs2119882 in MTNR1A and rs10830963 in MTNR1B are associated with an increased risk of developing GDM and insulin resistance in Han Chinese women. © 2013 S. Karger AG, Basel.
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Thiol-addition reactions and their applications in thiol recognition.
Chem Soc Rev
PUBLISHED: 05-23-2013
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Because of the biological importance of thiols, the development of probes for thiols has been an active research area in recent years. In this review, we summarize the results of recent exciting reports regarding thiol-addition reactions and their applications in thiol recognition. The examples reported can be classified into four reaction types including 1,1, 1,2, 1,3, 1,4 addition reactions, according to their addition mechanisms, based on different Michael acceptors. In all cases, the reactions are coupled to color and/or emission changes, although some examples dealing with electrochemical recognition have also been included. The use of thiol-addition reactions is a very simple and straightforward procedure for the preparation of thiol-sensing probes.
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Syntactic priming in Chinese sentence comprehension: evidence from event-related potentials.
Brain Cogn
PUBLISHED: 05-12-2013
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Using the event-related potential (ERP) technique, this study examined the nature of syntactic priming effects in Chinese. Participants were required to read prime-target sentence pairs each embedding an ambiguous relative clause (RC) containing either the same verb or a synonymous verb. In Chinese, the word de serves as a relative clause marker. During reading a potential Chinese RC structure (either the prime or the target sentence), Chinese readers initially expect to read an subject-verb-object (SVO) structure but the encounter of a relative clause marker de would make readers abandon the initial strategy and reanalyze the structure as a relative clause. A reduced P600 effect was elicited by the critical word de in the target sentence containing the same initial verb as in the prime sentence. No significant reduction of the P600 was observed in the target sentences in the synonymous condition. The results demonstrated that verb repetition but not similarity in meaning produced a syntactic priming effect in Chinese. The constraint-based lexicalist hypothesis and the argument structure theory were adopted to explain the syntactic priming effect obtained in the current study.
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Parathyroidectomy and heart rate variability in patients with stage 5 CKD.
Clin J Am Soc Nephrol
PUBLISHED: 05-09-2013
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Lower heart rate variability implies increased risk of cardiovascular disease. This study aimed to evaluate the relationship between mineral metabolism and heart rate variability and longitudinal changes of heart rate variability after parathyroidectomy in stage 5 CKD patients.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.