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Find video protocols related to scientific articles indexed in Pubmed.
Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
Mol. Cancer Ther.
PUBLISHED: 11-09-2014
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Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and is previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. beta-catenin was determined by immunohistochemistry, PAF levels by ELISA and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared to WT mice. While all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared to WT mice, cytosol expression of beta-catenin was significantly decreased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion lack of alk-SMase markedly increases AOM/DSS induced colonic tumorigenesis associated with decreased ceramide and increased sphingosine-1-phosphate and PAF levels.
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Discrete Nanoparticle-BSA Conjugates Manipulated by Hydrophobic Interaction.
ACS Appl Mater Interfaces
PUBLISHED: 11-06-2014
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Nanoparticle-protein conjugates are promising probes for biological diagnostics as well as versatile building blocks for nanotechnology. Here we demonstrate a facile method to prepare nanoparticles bearing discrete numbers of BSA simply by physical adsorption and electrophoretic isolation, in which the specific amphiphilic properties of BSA play important roles and the number of adsorbed BSA molecules can also be manipulated by tuning the coating extent of nanoparticles by amphiphilic polymer.
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The Mitochondrial Complex V-Associated Large-Conductance Inner Membrane Current Is Regulated by Cyclosporine and Dexpramipexole.
Mol. Pharmacol.
PUBLISHED: 10-20-2014
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Inefficiency of oxidative phosphorylation can result from futile leak conductance through the inner mitochondrial membrane. Stress or injury may exacerbate this leak conductance, putting cells, and particularly neurons, at risk of dysfunction and even death when energy demand exceeds cellular energy production. Using a novel method, we have recently described an ion conductance consistent with mitochondrial permeability transition pore (mPTP) within the c-subunit of the ATP synthase. Excitotoxicity, reactive oxygen species-producing stimuli, or elevated mitochondrial matrix calcium opens the channel, which is inhibited by cyclosporine A and ATP/ADP. Here we show that ATP and the neuroprotective drug dexpramipexole (DEX) inhibited an ion conductance consistent with this c-subunit channel (mPTP) in brain-derived submitochondrial vesicles (SMVs) enriched for F1FO ATP synthase (complex V). Treatment of SMVs with urea denatured extramembrane components of complex V, eliminated DEX- but not ATP-mediated current inhibition, and reduced binding of [(14)C]DEX. Direct effects of DEX on the synthesis and hydrolysis of ATP by complex V suggest that interaction of the compound with its target results in functional conformational changes in the enzyme complex. [(14)C]DEX bound specifically to purified recombinant b and oligomycin sensitivity-conferring protein subunits of the mitochondrial F1FO ATP synthase. Previous data indicate that DEX increased the efficiency of energy production in cells, including neurons. Taken together, these studies suggest that modulation of a complex V-associated inner mitochondrial membrane current is metabolically important and may represent an avenue for the development of new therapeutics for neurodegenerative disorders.
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Electron beam excitation of surface plasmon polaritons.
Opt Express
PUBLISHED: 10-17-2014
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In this paper, the excitations of surface plasmon polaritons (SPPs) by both perpendicular and parallel electron beam are investigated. The results of analytical theory and numerical calculation show that the mechanisms of these two excitations are essentially different, and the behavior and properties of SPPs in metal structures strongly depend on the methods of excitation. For the perpendicular excitation, SPPs contain plenty of frequency components, propagate with attenuation and are always accompanied with the transition radiation. Whereas for parallel excitation, SPPs waves are coherent, tunable, propagating without attenuation and the transition radiation does not occur. We also show that there are two modes for the parallel excited SPPs on the metal films and they all can be excited efficiently by the parallel moving electron beam. And the operating frequency of SPPs can be tuned in a large frequency range by adjusting the beam energy.
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Synthesis, properties and drug potential of the photosensitive alkyl- and alkylsiloxy-ligated silicon phthalocyanine Pc 227.
Photochem. Photobiol. Sci.
PUBLISHED: 10-13-2014
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The photosensitive, alkyl- and alkylsiloxy-ligated silicon phthalocyanine, SiPc[(CH2)3SH][OSi(CH3)2(CH2)3N(CH3)2], Pc 227, has been prepared and characterized. This phthalocyanine yields the experimental photodynamic therapy (PDT) drug Pc 4, SiPc[OH][OSi(CH3)2(CH2)3N(CH3)2], when irradiated with red light. To provide an understanding of the process by which Pc 227 and other alkyl-alkylsiloxysilicon phthalocyanines such as Pc 227 are photolyzed, bond dissociation energy, natural bond orbital (NBO) charge distribution, spin density distribution, nucleus-independent chemical shift (NICS), and electron localization function (ELF) calculations have been carried out on two models related to it. These show that the lowest energy pathway for the photolysis of Pc 227 is a homolysis involving a phthalocyanine ? radical having a low SiPc-C bond dissociation energy. The promise of the results of this study for synthetic chemistry and drug development is discussed.
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Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment.
J Zhejiang Univ Sci B
PUBLISHED: 10-09-2014
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Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.
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Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus.
J Diabetes
PUBLISHED: 10-01-2014
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To investigate the effects of acarbose add-on therapy on gut microbiota and inflammatory cytokines in Chinese patients with type 2 diabetes mellitus (DM).
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Corticosterone Mediates the Inhibitory Effect of Restraint Stress on the Migration of Mesenchymal Stem Cell to Carbon Tetrachloride-Induced Fibrotic Liver by Downregulating CXCR4/7 Expression.
Stem Cells Dev.
PUBLISHED: 10-01-2014
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Recent studies have revealed that mesenchymal stem cells (MSCs) have a great potential in therapeutic applications. The low efficiency of MSC recruitment and homing to sites of diseased organ tissue, however, remains a major hurdle in their application for treatment of diseases. Stress is commonly associated with various diseases. At the present time, little information is available about the effect of stress on MSC function. Here, we employed a carbon tetrachloride (CCl4)-induced mouse liver fibrosis model to investigate whether constraint stress affects the migration of MSCs to fibrotic liver. MSC homing to the fibrotic liver was significantly inhibited in mice with restraint stress. Restraint stress induced an elevation of corticosterone level in the serum. Blocking glucocorticoid signaling with either corticosterone-synthesis inhibitor metyrapone (MET) or glucocorticoid receptor antagonist RU486 attenuated restraint stress-induced inhibition of MSCs migration. The serum concentration of stromal cell-derived factor-1 (SDF-1) increased in mice treated with CCl4. Restraint stress had no influence on expression of SDF-1 and hepatocyte growth factor (HGF) in the fibrotic liver. Culture with the serum of CCl4-treated mice or SDF-1 promoted MSC migration, which was suppressed by corticosterone. Exposure of MSCs to corticosterone decreased their expression of C-X-C chemokine receptor type 4 (CXCR4) and C-X-C chemokine receptor type 7 (CXCR7). These results demonstrate that the inhibitory effect of corticosterone on MSC migration might be mediated via decreasing the expression of CXCR4 and CXCR7 in MSCs. Interventions targeting the interaction between corticosterone and its receptor improve migration and homing of MSCs in hosts receiving transplantation of these cells.
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[Determination of Si and P in MnZn ferrites by inductively coupled plasma mass spectrometry].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 09-12-2014
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An inductively coupled plasma mass spectrometry (ICP-MS) was developed for the determination of Si and P in MnZn ferrites. The sample was digested by HNO3 + HCl with microwave digestion followed by dilution with ultrapure water then the above two elements in the solution were analyzed directly by ICP-MS. The analytical elements were by introducing the helium gas into the octopole reaction system (ORS) to eliminate the polyatomic interferences caused by the high salty matrixes. The matrix effects and the instrument drift could be commendably calibrated with Y as internal standard element. The working parameters of the instrument were optimized. The NIST SRM 362 and NIST SRM 364 were used as standard reference materials. The results showed a good agreement between the certified values and the experimental results for three analytes. The detection limits for Si and P is 0.91 and 0.27 microg x L(-1).
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Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1?/miR-210/Bcl-2 pathway in colon cancer cells.
Int. J. Oncol.
PUBLISHED: 09-11-2014
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Autophagy is an evolutionarily conserved cellular response to conditions of stress such as hypoxia, which induce radioresistance in cancer cells. We studied the mechanism of action of hypoxia on autophagy and radiosensitivity in colon cancer cells. In the human colon cancer cell lines SW480 and SW620, autophagosomes were analyzed to evaluate autophagy by flow cytometry. The expression of hypoxia inducible factor-1? (HIF-1?), Bcl-2, and miR-210 was detected by western blotting and quantitative real-time polymerase chain reaction (PCR). HIF-1? and miR-210 inhibition was induced by siRNA transfections. Apoptosis detection and colony assays were performed to determine radiosensitivity. HIF-1? and miR-210 showed a significant increase under hypoxic condition. The inhibition of HIF-1? decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1? induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. Our results imply that autophagy contributes to the reduction of radiosensitivity in hypoxic environment, and the process is mediated through the HIF-1?/miR-210/Bcl-2 pathway in human colon cancer cells.
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[Lower grade chronic inflammation is associated with obstructive sleep apnea syndrome in type 2 diabetes mellitus].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 09-10-2014
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To investigate whether the existence of obstructive sleep apnea syndrome (OSAS) in patients with type 2 diabetes (T2DM) is associated with low grade chronic inflammation.
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Roles of SATB2 in Site-Specific Stemness, Autophagy and Senescence of Bone Marrow Mesenchymal Stem Cells.
J. Cell. Physiol.
PUBLISHED: 09-09-2014
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Craniofacial bone marrow mesenchymal stem cells (BMSCs) display some site-specific properties that differ from those of BMSCs derived from the trunk and appendicular skeleton, but the characteristics of craniofacial BMSCs and the mechanisms that underlie their properties are not completely understood. Previous studies indicated that special AT-rich binding protein 2 (SATB2) may be a potential regulator of craniofacial skeletal patterning and site-specific osteogenic capacity. Here, we investigated the stemness, autophagy, and anti-aging capacity of mandible-derived BMSCs (M-BMSCs) and tibia-derived BMSCs (T-BMSCs) and explored the role of SATB2 in regulating these properties. M-BMSCs not only possessed stronger expression of SATB2 and stemness markers (pluripotency genes, such as Nanog, OCT-4, Sox2, and Nestin) but also exhibited stronger autophagy and anti-aging capacities under normal or hypoxia/serum deprivation conditions compared to T-BMSCs. Exogenous expression of SATB2 in T-BMSCs significantly enhanced the expression of pluripotency genes as well as autophagy and anti-aging capacity. Moreover, SATB2 markedly enhanced osteogenic differentiation of BMSCs in vitro, and promoted bone defect regeneration and the survival of BMSCs that were transplanted into mandibles with critical size defects. Mechanistically, SATB2 upregulates pluripotency genes and autophagy-related genes, which in turn activate the mechanistic target of rapamycin signaling pathway. Collectively, our results provide novel evidence that site-specific BMSCs have distinct biological properties and suggest that SATB2 plays a potential role in regulating the stemness, autophagy, and anti-aging properties of craniofacial BMSCs. The application of SATB2 to manipulate stem cells for the reconstruction of bone defects might represent a new approach. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
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Effect of ermiao fang with xixin (herba asari mandshurici) on bone marrow stem cell directional homing to a focal zone in an osteoarthritis rat model.
J Tradit Chin Med
PUBLISHED: 09-05-2014
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To investigate the effects of Ermiao Fang (EM) with medical guide Xixin (Herba Asari Mandshurici) (HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis (OA) rats.
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Curcumin Protects against CCl4-Induced Liver Fibrosis in Rats by Inhibiting HIF-1? Through an ERK-Dependent Pathway.
Molecules
PUBLISHED: 09-04-2014
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The ERK/HIF-1? signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1? and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1?/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and ?-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1? and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1? partly through the ERK pathway.
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Dislocation creation and void nucleation in FCC ductile metals under tensile loading: A general microscopic picture.
Sci Rep
PUBLISHED: 09-01-2014
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Numerous theoretical and experimental efforts have been paid to describe and understand the dislocation and void nucleation processes that are fundamental for dynamic fracture modeling of strained metals. To date an essential physical picture on the self-organized atomic collective motions during dislocation creation, as well as the essential mechanisms for the void nucleation obscured by the extreme diversity in structural configurations around the void nucleation core, is still severely lacking in literature. Here, we depict the origin of dislocation creation and void nucleation during uniaxial high strain rate tensile processes in face-centered-cubic (FCC) ductile metals. We find that the dislocations are created through three distinguished stages: (i) Flattened octahedral structures (FOSs) are randomly activated by thermal fluctuations; (ii) The double-layer defect clusters are formed by self-organized stacking of FOSs on the close-packed plane; (iii) The stacking faults are formed and the Shockley partial dislocations are created from the double-layer defect clusters. Whereas, the void nucleation is shown to follow a two-stage description. We demonstrate that our findings on the origin of dislocation creation and void nucleation are universal for a variety of FCC ductile metals with low stacking fault energies.
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The lifetime cost of diabetes and its implications for diabetes prevention.
Diabetes Care
PUBLISHED: 08-23-2014
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To assess the cost implications of diabetes prevention, it is important to know the lifetime medical cost of people with diabetes relative to those without. We derived such estimates using data representative of the U.S. national population.
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Presence of notched QRS on paced electrocardiographs as a predictor of poor response to cardiac resynchronization therapy.
Chin. Med. J.
PUBLISHED: 08-23-2014
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Cardiac resynchronization therapy (CRT) on patients with advanced and refractory heart failure has made remarkable progress. Clinically, notched QRS (nQRS) is commonly seen on electrocardiographs (ECGs) with bundle branch block morphology and on paced ECGs after implantation of a CRT device, which may reflect the heterogeneity of ventricular myocardial depolarization and electrical activity. The aim of this study was to determine whether patients with more nQRS myocardial segments on paced ECGs had a worse response to CRT than patients with fewer nQRS myocardial segments.
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Comparison of MDCK-MDR1 and Caco-2 cell based permeability assays for anti-malarial drug screening and drug investigations.
J Pharmacol Toxicol Methods
PUBLISHED: 08-20-2014
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Malaria is a major health concern and affects over 300million people a year. Accordingly, there is an urgent need for new efficacious anti-malarial drugs. A major challenge in developing new anti-malarial drugs is to design active molecules that have preferable drug-like characteristics. These "drug-like" characteristics include physiochemical properties that affect drug absorption, distribution, metabolism, and excretion (ADME). Compounds with poor ADME profiles will likely fail in vivo due to poor pharmacokinetics and/or other drug delivery related issues. There have been numerous assays developed in order to pre-screen compounds that would likely fail in further development due to poor absorption properties including PAMPA, Caco-2, and MDCK permeability assays.
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Analysis of Th1/Th2 response pattern for erythrodermic psoriasis.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 08-19-2014
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As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis (EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells (PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-?, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris (PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-?, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls (P<0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients (P<0.01). The ratios of IFN-?/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.
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Expression levels of autophagy related proteins and their prognostic significance in retinocytoma and retinoblastoma.
Int J Ophthalmol
PUBLISHED: 08-18-2014
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To discuss the prognostic significant of autophagy related proteins (ARPs) in retinoblastoma (RB) and to find the molecular marker to distinguish retinocytoma (RC) and RB by investigating the different expression profiling of microtubule-associated protein light chain 3 (LC3B) and other ARPs in RC and RB.
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A Monoclonal Antibody Against PMEL.
Monoclon Antib Immunodiagn Immunother
PUBLISHED: 08-13-2014
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PMEL, also known as Pmel17 or gp100, is a melanocyte-specific glycoprotein that is essential for the formation of stage II melanosomes. As it has a highly restricted expression pattern in normal tissues and a transient presence on the cell surface, PMEL is believed to be a potential target for antibody drug conjugate therapy in some pigmentary diseases. The production of a high specificity and high affinity monoclonal antibody against human PMEL was helpful for the antibody drug conjugate therapy study. In the present study, monoclonal antibodies (MAbs) against PMEL were obtained by immunizing BALB/c mice with the recombinant PMEL-GST fusion protein. Three mAbs (A3F, G11B, and J7E) with a titer of 1:6000, 1:10,000, and 1:3000, respectively, were obtained. Immunoglobulin subclass assay revealed that A3F was IgG2b, G11B was IgG1, and J7E was IgG2a. Specificity analysis by Western blotting demonstrated that A3F and J7E cross-reacted with GPNMB or LAMP; however, G11B reacted with PMEL only. Immunohistochemistry experiments showed that G11B could bind human PMEL antigen in normal skin. Flow cytometry assay demonstrated that G11B could bind to the surface of PMEL positive melanoma cells but not PMEL negative cells. Taken together, these results show that this G11B provides a useful tool for the antibody drug conjugate therapy study in some pigmentary diseases.
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Non-SMC condensin I complex, subunit D2 gene polymorphisms are associated with Parkinson's disease: a Han Chinese study.
Genome
PUBLISHED: 08-11-2014
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Previous studies have indicated that non-SMC condensin I complex, subunit D2 (NCAPD2), an important protein in chromosome condensation, gene polymorphisms are associated with Alzheimer's disease. But no study has shown the relationship between NCAPD2 polymorphisms and Parkinson's disease. Here, we conducted a case-control study to investigate the relationship between NCAPD2 polymorphisms and the risk of Parkinson's disease in a Han Chinese population. Two single nuclear polymorphisms (SNPs) of NCAPD2 (rs7311174 and rs2072374) showed significant p values (p = 0.046 and p = 0.043, respectively) in 265 patients and 267 controls. Further analysis showed an effect of age and gender on the relationship between the two SNPs and the risk for Parkinson's disease. The A allele of rs7311174 and the T allele of rs2072374 were protective in the male patients (p = 0.016 and p = 0.019, respectively). The frequencies of the T allele of rs7311174 and the C allele of rs2072374 were significantly associated with late-onset Parkinson's disease (p = 0.048 and p = 0.044, respectively). This research demonstrates a positive relationship between the NCAPD2 gene and the risk for Parkinson's disease in a Han Chinese population and provides a potential genetic marker for sporadic Parkinson's disease.
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The Roles of the RII? Linker and N-terminal Cyclic Nucleotide-binding Domain in Determining the Unique Structures of the Type II? Protein Kinase A: A SMALL ANGLE X-RAY AND NEUTRON SCATTERING STUDY.
J. Biol. Chem.
PUBLISHED: 08-11-2014
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Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. The PKA holoenzyme is a tetramer (R2:C2), with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits; binding of cAMP to the regulatory subunit homodimer causes activation of the catalytic subunits. Four different R subunit isoforms exist in mammalian cells, and these confer different structural features, subcellular localization, and biochemical properties upon the PKA holoenzymes they form. The holoenzyme containing RII? is structurally unique in that the type II? holoenzyme is much more compact than the free RII? homodimer. We have used small angle x-ray scattering and small angle neutron scattering to study the solution structure and subunit organization of a holoenzyme containing an RII? C-terminal deletion mutant (RII?(1-280)), which is missing the C-terminal cAMP-binding domain to better understand the structural organization of the type II? holoenzyme and the RII? domains that contribute to stabilizing the holoenzyme conformation. Our results demonstrate that compaction of the type II? holoenzyme does not require the C-terminal cAMP-binding domain but rather involves large structural rearrangements within the linker and N-terminal cyclic nucleotide-binding domain of the RII? homodimer. The structural rearrangements are significantly greater than seen previously with RII? and are likely to be important in mediating short range and long range interdomain and intersubunit interactions that uniquely regulate the activity of the type II? isoform of PKA.
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Notch signaling in blood vessels: from morphogenesis to homeostasis.
Sci China Life Sci
PUBLISHED: 08-08-2014
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Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology. Compelling evidence indicates that Notch signaling is vital for vascular morphogenesis including arterial and venous differentiation and endothelial tip and stalk cell specification during sprouting angiogenesis and also vessel maturation featured by mural cell differentiation and recruitment. Notch signaling is also required for vascular homeostasis in adults by keeping quiescent phalanx cells from re-entering cell cycle and by modulating the behavior of endothelial progenitor cells. We will summarize recent advances of Notch pathway in vascular biology with special emphasis on the underlying molecular mechanisms.
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Limonoids from the Leaves and Twigs of Walsura yunnanensis.
J. Nat. Prod.
PUBLISHED: 07-31-2014
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Nine new cedrelone limonoids, namely, walsuranolide B (1), 11?-hydroxy-23-O-methylwalsuranolide (2), yunnanolide A (3), yunnanol A (4), 11?-hydroxyisowalsuranolide (5), 11?-hydroxy-1,2-dihydroisowalsuranolide (6), 1?,11?-dihydroxy-1,2-dihydroisowalsuranolide (7), 11?-hydroxy-1?-methoxy-1,2-dihydroisowalsuranolide (8), and yunnanolide B (9), together with a new cycloartane triterpenoid, (24S*,25R*)-cycloartane-3?,24,25,26-tetrol (10), were isolated from the leaves and twigs of Walsura yunnanensis. Their structures were elucidated on the basis of spectroscopic analysis and by comparison with literature data. Compounds 3 and 5 exhibited potent cytotoxicity against five human tumor cell lines with IC50 values in the range 2.2-4.2 ?M.
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Mathematical modeling for novel cancer drug discovery and development.
Expert Opin Drug Discov
PUBLISHED: 07-25-2014
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Mathematical modeling enables: the in silico classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silico pre-screened drug targets can be validated by a small number of carefully selected experiments.
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[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 07-23-2014
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To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.
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RTN4 3'-UTR insertion/deletion polymorphism and susceptibility to non-small cell lung cancer in Chinese Han population.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-22-2014
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Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.
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Schwann cells originating from skin-derived precursors promote peripheral nerve regeneration in rats.
Neural Regen Res
PUBLISHED: 07-21-2014
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Artificial guidance channels containing Schwann cells can promote the regeneration of injured peripheral nerve over long distances. However, primary Schwann cells are not suitable for autotransplantation. Under specific conditions, skin-derived progenitors can be induced to differentiate into Schwann cells. Therefore, adult rat dorsal skin (dermis)-derived progenitors were isolated and induced to differentiate with DMEM/F12 containing B27, neuregulin 1, and forskolin. Immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR) confirmed that the resultant cells were indeed Schwann cells. Artificial guidance channels containing skin-derived progenitors, Schwann cells originating from skin-derived progenitors, or primary Schwann cells were used to bridge 5 mm sciatic nerve defects. Schwann cells originating from skin-derived progenitors significantly promoted sciatic nerve axonal regeneration. The significant recovery of injured rat sciatic nerve function after the transplantation of Schwann cells originating from skin-derived progenitors was confirmed by electromyogram. The therapeutic effect of Schwann cells originating from skin-derived progenitors was better than that of skin-derived progenitors. These findings indicate that Schwann cells originating from skin-derived precursors can promote peripheral nerve regeneration in rats.
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Aberrant sonic hedgehog signaling pathway and STAT3 activation in papillary thyroid cancer.
Int J Clin Exp Med
PUBLISHED: 07-15-2014
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The sonic hedgehog (SHH) and STAT3 signaling pathways play important roles during carcinogenesis with possible interaction. To determine the association of the activation of SHH signaling pathway and STAT3 pathway in carcinogenesis of human papillary thyroid cancer (PTC), we examined the expression of SHH signaling pathway molecules including SHH, Patched (PTCH), Smoothened (SMO) and GLI1 (glioma-associated oncogene homolog 1), as well as p-STAT3 (phosphorylation at Tyr705) by immunohistochemistry in 164 cases of PTC. In PTC, 70.12%, 64.02%, 68.90%, 64.02%, and 56.71% and in the adjacent normal thyroid tissues, 18.29%, 18.90%, 26.83%, 14.63%, and 10.98% of the specimens stained positive for SHH, PTCH, SMO, GLI1, and p-STAT3, respectively. Significant difference were found for the positive rate of SHH, PTCH, SMO, and GLI1 as well as p-STAT3 expression between PTC and adjacent normal thyroid tissues. There was a high accordance rate between SHH, PTCH, SMO, and GLI1 expression and all of them positively correlated with larger tumor size, the presence of ETE and LNM, and higher TNM stage. P-STAT3 expression positively correlated with the presence of ETE and LNM, and higher TNM stage but not age, gender, tumor size of the PTC patients. Signifi cant positive correlation between p-STAT3 and SHH, PTCH, SMO and GLI expression was found in PTC. These findings suggest that the SHH and STAT3 signaling pathways are frequently activated in PTC, interact with each other and may therefore be indicators for prognosis or potential targets for therapy against PTC.
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Determination of goitrogenic metabolites in the serum of male wistar rat fed structurally different glucosinolates.
Toxicol Res
PUBLISHED: 06-11-2014
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Glucosinolates (GLSs) are abundant in cruciferous vegetables and reported to have anti thyroidal effects. Four GLSs (sinigrin, progoitrin, glucoerucin, and glucotropaeolin) were administered orally to rats, and the breakdown products of GLSs (GLS-BPs: thiocyanate ions, cyanide ions, organic isothiocyanates, organic nitriles, and organic thiocyanates) were measured in serum. Thiocyanate ions were measured by colorimetric method, and cyanide ions were measured with CI-GC-MS. Organic isothiocyanates and their metabolites were measured with the cyclocondensation assay. Organic nitriles and organic thiocyanates were measured with EI-GC-MS. In all treatment groups except for progoitrin, thiocyanate ions were the highest among the five GLS-BPs. In the progoitrin treated group, a high concentration of organic isothiocyanates (goitrin) was detected. In the glucoerucin treated group, a relatively low amount of goitrogenic substances was observed. The metabolism to thiocyanate ions happened within five hours of the administration, and the distribution of GLSs varied with the side chain. GLSs with side chains that can form stable carbocation seemed to facilitate the degradation reaction and produce a large amount of goitrogenic thiocyanate ions. Because goitrogenic metabolites can be formed without myrosinase, the inactivation of myrosinase during cooking would have no effect on the anti-nutritional effect of GLSs in cruciferous vegetables.
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Prognostic role of Twist or Snail in various carcinomas: a systematic review and meta-analysis.
Eur. J. Clin. Invest.
PUBLISHED: 06-06-2014
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Twist and Snail are considered as key transcriptional repressors of E-cadherin tightly related to epithelial-to-mesenchymal transition (EMT) and cancer progression. Numerous studies have investigated the prognostic value of Twist and Snail. However, the published results were controversial or even opposite. Our article aimed to evaluate the prognostic role of Twist and Snail in patients with cancer.
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Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study.
J Clin Hypertens (Greenwich)
PUBLISHED: 05-13-2014
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The purpose of this study was to evaluate the effects of spironolactone on dialysis patients with refractory hypertension and possible adverse effects. This was a 12-week prospective, randomized, double-blind trial of 82 patients randomly assigned to 12-week treatment with 25 mg/d spironolactone or placebo as add-on therapy. Visits were scheduled at the start of treatment and after 12 weeks. Measurements of 24-hour ambulatory blood pressure (BP) monitoring and morning BP were performed. After 12 weeks, spironolactone significantly improved refractory hypertension. Average placebo-corrected morning BP was reduced by 16.7/7.6 mm Hg. Mean 24-hour ambulatory BP was reduced by 10.9/5.8 mm Hg. In contrast, serum aldosterone levels in the spironolactone group slightly increased and serum potassium levels insignificantly increased. This study has demonstrated that spironolactone (50 mg) safely and effectively reduces BP in patients with refractory hypertension undergoing dialysis.
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Low-dose paclitaxel improves the therapeutic efficacy of recombinant adenovirus encoding CCL21 chemokine against murine cancer.
Cancer Sci.
PUBLISHED: 05-09-2014
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Secondary lymphoid tissue chemokine (SLC/CCL21), one of the CC chemokines, exerts potent antitumor immunity by co-localizing T cells and dendritic cells at the tumor site and is currently tested against human solid tumors. Here, we investigated whether the combination of recombinant adenovirus encoding murine CCL21 (Ad-mCCL21) with low-dose paclitaxel would improve therapeutic efficacy against murine cancer. Immunocompetent mice bearing B16-F10 melanoma or 4T1 breast carcinoma were treated with either Ad-mCCL21, paclitaxel, or both agents together. Our results showed that Ad-mCCL21 + low-dose paclitaxel more effectively reduced the growth of tumors as compared with either treatment alone and significantly prolonged survival time of the tumor-bearing animals. These antitumor effects of the combined therapy were linked to altered cytokine network at the tumor site, enhanced apoptosis of tumor cells, and decreased formation of new vessels in tumors. Importantly, the combined therapy elicited a strong therapeutic antitumor immunity, which could be partly abrogated by the depletion of CD4(+) or CD8(+) T lymphocytes. Collectively, these preclinical evaluations may provide a combined strategy for antitumor immunity and should be considered for testing in clinical trials.
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Quantum molecular dynamics study of expanded beryllium: evolution from warm dense matter to atomic fluid.
Sci Rep
PUBLISHED: 05-06-2014
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By performing quantum molecular dynamics (QMD) simulations, we investigate the equation of states, electrical and optical properties of the expanded beryllium at densities two to one-hundred lower than the normal solid density, and temperatures ranging from 5000 to 30000 K. With decreasing the density of Be, the optical response evolves from the one characteristic of a simple metal to the one of an atomic fluid. By fitting the optical conductivity spectra with the Drude-Smith model, it is found that the conducting electrons become localized at lower densities. In addition, the negative derivative of the electrical resistivity on temperature at density about eight lower than the normal solid density demonstrates that the metal to nonmetal transition takes place in the expanded Be. To interpret this transition, the electronic density of states is analyzed systematically. Furthermore, a direct comparison of the Rosseland opacity obtained by using QMD and the standard opacity code demonstrates that QMD provides a powerful tool to validate plasma models used in atomic physics approaches in the warm dense matter regime.
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Proteome changes in mesenteric lymph induced by sepsis.
Mol Med Rep
PUBLISHED: 05-02-2014
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The present study aimed to examine the changes in mesenteric lymph during the development of sepsis and to identify the distinct proteins involved, as targets for further study. The sepsis animal model was constructed by cecal ligation and puncture (CLP). The mesenteric lymph was collected from 28 adult male Sprague?Dawley rats, which were randomly divided into the following four groups (n=7 per group): CLP?6 h, CLP?24 h, sham?6 h and sham?24 h groups. Capillary high performance liquid chromatography?tandem mass spectrometry was performed to analyze the proteome in mesenteric lymph. A comprehensive bioinformatic analysis was then conducted to investigate the distinct proteins. Compared with the sham group, 158 distinct proteins were identified in the lymph samples from the CLP group. Five of these proteins associated with the same lipid metabolism pathway were selected, apolipoprotein E (ApoE), annexin A1 (Anxa1), neutrophil gelatinase?associated lipocalin (NGAL), S100a8 and S100a9. The expression of ApoE, Anxa1, NGAL, S100a8 and S100a9 were all elevated in the progression of sepsis. The five proteins were reported to be closely associated with disease development and may be a potential target for the diagnosis and treatment of sepsis. In conclusion, identifying proteome changes in mesenteric lymph provides a novel perspective to understand the pathological mechanisms underlying sepsis.
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Critical role of cellular glutathione homeostasis for trivalent inorganic arsenite-induced oxidative damage in human bronchial epithelial cells.
Mutat Res Genet Toxicol Environ Mutagen
PUBLISHED: 04-28-2014
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Trivalent inorganic arsenic (iAs(3+)) is a powerful carcinogen that enhances the risk of lung cancer. Paradoxically, iAs(3+) also shows substantial efficacy in the treatment of lung tumors. However, the exact molecular mechanisms underlying iAs(3+)-induced toxicity and therapeutic effect in lung remain unclear. In this study, the effects of iAs(3+), sodium arsenite (NaAsO2) and arsenic trioxide (As2O3), on cell viability, apoptosis, genotoxicity and oxidative stress in cultured human bronchial epithelial cells were observed. Our results showed that NaAsO2 and As2O3 exposure could result in defects in cell proliferation and greatly enhance the level of oxidative damage. To clarify the critical role of glutathione (GSH) homeostasis in oxidative damage induced by iAs(3+), we further measured the content of GSH, ratio of GSH to GSSG, and the activities of GSH-related enzymes involved in the process of GSH synthesis, recycling and utilization. Our data demonstrated that NaAsO2 and As2O3 disrupted the balance of GSH homeostasis, and NaAsO2- and As2O3-induced oxidative damage was closely associated with the imbalance in GSH synthesis, recycling and utilization. To better understand the physiologic significance of Nrf2 in maintaining GSH-homeostasis, the expression level of Nrf2 was measured after iAs(3+) exposure. We found that the protein expression levels of Nrf2 were increased in both NaAsO2- and As2O3-treated cells. Collectively, our findings suggest that disturbed Nrf2-regulated GSH-homeostasis is associated with the oxidative damage triggered by iAs(3+), and loss of GSH homeostasis might implicate in both the pathogenesis of iAs(3+)-induced lung diseases and anticancer activity of iAs(3+).
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Suppressor of fused (Sufu) represses Gli1 transcription and nuclear accumulation, inhibits glioma cell proliferation, invasion and vasculogenic mimicry, improving glioma chemo-sensitivity and prognosis.
Oncotarget
PUBLISHED: 04-27-2014
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Glioblastoma are highly aggressive brain tumors with poor prognosis. While various dysregulation of signaling pathways in gliomas have been described, the identification of biomarkers and therapy targets remains an important task for novel diagnostic and therapeutic approaches. Here we described that the Suppressor of fused (also known as Sufu) is significantly down-regulated in high-grade gliomas, correlating with a poor prognosis. We demonstrated that ectopic expression of Sufu inhibited cell proliferation, invasion and vasculogenic mimicry. In addition, overexpression of Sufu reduced Gli reporter gene transcription activity and prevented Gli1 nuclear accumulation, whereas knockdown of Sufu reversed these effects. Furthermore, overexpressed Sufu sensitized glioblastoma to Temozolomide and Cyclopamine. Thus, Sufu is potential tumor suppressor and therapeutic target in glioblastoma.
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Activation of TLR9-dependent p38MAPK pathway in the pathogenesis of primary Sjögren's syndrome in NOD/Ltj mouse.
J. Oral Pathol. Med.
PUBLISHED: 04-21-2014
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The objective of this study was to investigate the potential role of Toll-like receptor 9-dependent p38 MAPK signaling pathway in the pathogenesis of primary Sjögren's syndrome (pSS) in NOD/Ltj mouse, aiming to identify an ideal target therapy model for human pSS.
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Dengue Virus Upregulates Expression of Notch Ligands Dll1 and Dll4 Through IFN-? Signaling Pathway.
Immunology
PUBLISHED: 04-17-2014
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Notch signaling pathway is involved in multiple cellular processes and has been recently indicated to modulate host immune response. However, role of Notch pathway in dengue virus (DENV) infection remains unknown. Our study has screened the expression profile of Notch receptors, ligands and target genes in human monocytes, macrophages and dendritic cells (DCs) in response to DENV infection. The Real-time PCR data showed that Notch ligand Dll1 was significantly induced in DENV-infected monocytes; and receptor Notch4, ligands Dll1 and Dll4, and target Hes1 were dramatically enhanced in DENV-infected macrophages and DCs. In macrophages, induction of Dll1 and Dll4 mediated by DENV2 was increased by treatment of IFN-?, and was impaired by neutralization of IFN-?. The DENV-induced Dll1 and Dll4 expression level was decreased by silencing of key innate immune molecules, including TLR3, MyD88, RIG-I or IPS-I. In IFN-receptor depleted macrophages, the Dll1 and Dll4 induction was significantly alleviated. Functionally, activation of Notch signaling by Dll1 in CD4(+) T cells enhanced the expression of a Th1 cytokine IFN-?, while Notch activation in macrophages had no direct effect in replication of DENV. Our data revealed that the expressions of Notch ligands in antigen presenting cells were differentially induced by DENV via innate immune signaling, which is important for Th1/Th2 differentiation during adaptive immune response. This article is protected by copyright. All rights reserved.
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Attenuated inhibition of medium spiny neurons participates in the pathogenesis of childhood depression.
Neural Regen Res
PUBLISHED: 04-11-2014
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Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of antidepressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental findings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.
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Endothelial differentiation of diabetic adipose-derived stem cells.
J. Surg. Res.
PUBLISHED: 03-23-2014
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Diabetic (DM) patients frequently lack autologous vascular tissue required for revascularization procedures and dialysis access creation. We have developed a tissue-engineered graft that uses adipose-derived stem cells (ASC) as endothelial cell substitutes. Here, we compare DM versus nondiabetic (NDM) ASC in terms of isolation efficiency, proliferation, commitment toward endothelial lineage, and seeding onto the luminal surface of a graft.
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HMGN2, a new anti-tumor effector molecule of CD8? T cells.
Mol. Cancer
PUBLISHED: 03-03-2014
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Cytolytic T lymphocytes (CTL) and natural killer (NK) cells have been implicated as important cells in antitumor responses. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2) could be released by IL-2 and PHA stimulated peripheral blood mononuclear cells (PBMCs) and also induced tumor cells apoptosis at low doses. In this study, we isolated and cultured PBMCs and CD8? T cells to analyze the expression and antitumor effects of HMGN2.
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The capsid protein p38 of turnip crinkle virus is associated with the suppression of cucumber mosaic virus in Arabidopsis thaliana co-infected with cucumber mosaic virus and turnip crinkle virus.
Virology
PUBLISHED: 02-28-2014
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Infection of plants by multiple viruses is common in nature. Cucumber mosaic virus (CMV) and Turnip crinkle virus (TCV) belong to different families, but Arabidopsis thaliana and Nicotiana benthamiana are commonly shared hosts for both viruses. In this study, we found that TCV provides effective resistance to infection by CMV in Arabidopsis plants co-infected by both viruses, and this antagonistic effect is much weaker when the two viruses are inoculated into different leaves of the same plant. However, similar antagonism is not observed in N. benthamiana plants. We further demonstrate that disrupting the RNA silencing-mediated defense of the Arabidopsis host does not affect this antagonism, but capsid protein (CP or p38)-defective mutant TCV loses the ability to repress CMV, suggesting that TCV CP plays an important role in the antagonistic effect of TCV toward CMV in Arabidopsis plants co-infected with both viruses.
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Quantum molecular dynamics study of warm dense iron.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 02-06-2014
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The equation of state, the self-diffusion coefficient and viscosity of fluid iron in the warm dense regime at densities from 12.5 to 25.0g/cm^{3}, and temperatures from 0.5 to 15.0 eV have been calculated via quantum molecular dynamics simulations. The principal Hugoniot is in good agreement with nuclear explosive experiments up to ?50Mbar but predicts lower pressures compared with high intensity laser results. The self-diffusion coefficient and viscosity have been simulated and have been compared with the one-component plasma model. The Stokes-Einstein relationship, defined by connections between the viscosity and the self-diffusion coefficient, has been determined and has been found to be fairly well described by classical predictions.
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TCAB1: a potential target for diagnosis and therapy of head and neck carcinomas.
Mol. Cancer
PUBLISHED: 01-30-2014
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WRAP53, including ?, ? and ? isoforms, plays an important role not only in the stability of p53 mRNA, but also in the assembly and trafficking of the telomerase holoenzyme. It has been considered an oncogene and is thought to promote the survival of cancer cells. The aim of this study was to detect the role of TCAB1 (except WRAP53?) in the occurrence and development of head and neck carcinomas.
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Lithium chloride promotes the odontoblast differentiation of hair follicle neural crest cells by activating Wnt/?-catenin signaling.
Cell Biol. Int.
PUBLISHED: 01-26-2014
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The Wnt/?-catenin signalling pathway contributes to the maintenance of pluripotency and partial reprogramming of stem cells. Postnatal neural crest cells (NCCs) can differentiate into odontoblast-like cells due to their multi-potential property, but further endeavors need to be made to promote odontogenic differentiation of hair follicle neural crest cells (hfNCCs). This study investigated whether the Wnt pathway activator lithium chloride (LiCl) promotes odontoblast differentiation of hfNCCs. Change of proliferation, ?-catenin and pluripotency markers of hfNCCs were examined after treatment with LiCl. An in vitro odontoblast differentiation model of hfNCCs was built using dental cell conditioned media (DC-CM). The effects of LiCl on odontoblast differentiation of hfNCCs showed that proliferation and expression of ?-catenin in the cytosolic and nuclear compartments were increased in the LiCl-treated hfNCCs, and the pluripotency marks, Oct4, Klf4, Sox2 and Nanog, were more highly expressed in the LiCl-treated group than in the control group. The odontoblast markers such as DSP, DMP1 and Runx2, could be detected in hfNCCs induced by DC-CM, but in LiCl -treated group all three markers had stronger expression. Expression of ?-catenin in the nuclear of LiCl-treated hfNCCs induced by DC-CM was higher than in the other groups. The data indicate that the Wnt pathway activator LiCl can promote proliferation and odontoblast differentiation of hfNCCs, and chemical approaches are of benefit in obtaining more desirable seed cell types for cell-based therapies.
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Accuracy of early detection of colorectal tumours by stool methylation markers: A meta-analysis.
World J. Gastroenterol.
PUBLISHED: 01-24-2014
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To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours.
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EZH2, a potential regulator of dental pulp inflammation and regeneration.
J Endod
PUBLISHED: 01-21-2014
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Dental pulp has limited capability to regenerate, which happens in the early stage of pulpitis. An ambiguous relationship exists; inflammation may impair or support pulp regeneration. Epigenetics, which is involved in cell proliferation and inflammation, could regulate human dental pulp cell (HDPCs) regeneration. The aim of this study was to determine the role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2), in the inflammation, proliferation, and regeneration of dental pulp. We used trimethylated histone H3 lysine 27(H3K27me3) and its lysine demethylase 6B (KDM6B) to monitor functional effects of altered EZH2 levels.
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Prognostic significance of systemic inflammation-based lymphocyte- monocyte ratio in patients with lung cancer: based on a large cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275-1.816 for OS, and HR = 1.338, 95% CI: 1.152-1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520-2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946-3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.
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Sulfotransferase SULT1A1 Arg213His polymorphism with cancer risk: a meta-analysis of 53 case-control studies.
PLoS ONE
PUBLISHED: 01-01-2014
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The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis.
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[Effects of hemoperfusion on the patients with acute toxication of 2, 4-dinitrophenol].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-24-2013
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To explore the management strategies of acute toxication of 2, 4-dinitrophenol by hemoperfusion.
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The 7th pandemic Vibrio cholerae O1 El Tor isolate in China has undergone genetic shifts.
J. Clin. Microbiol.
PUBLISHED: 12-18-2013
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A total of 330 clinical Vibrio cholerae O1 serogroups dating between 1961 and 2010 from China were investigated.…
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Vibration responses of h-BN sheet to charge doping and external strain.
J Chem Phys
PUBLISHED: 12-11-2013
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Based on density functional theory and density functional perturbation theory calculations, we systematically investigate the vibration responses of h-BN sheet to charge doping and external strains. It is found that under hole doping, the phonon frequencies of the ZO and TO branches at different wave vector q shift linearly with different slopes. Under electron doping, although the phonon frequencies shift irregularly, the shifting values are different at different phonon wave vectors. Interestingly, we find that external strain can restrain the irregular vibration responses of h-BN sheet to electron doping. The critical factor is revealed to be the relative position of the nearly free electron and boron pz states of h-BN sheet. Under external strains, the vibration responses of h-BN sheet are also found to be highly dependent on the phonon branches. Different vibration modes at different q points are revealed to be responsible for the vibration responses of h-BN sheet to charge doping and external strain. Our results point out a new way to detect the doping or strain status of h-BN sheet by measuring the vibration frequencies at different wave vector.
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Inducible nitric oxide synthase inhibits oxygen consumption in collateral dependent myocardium.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 12-06-2013
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Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia which results in growth of collateral vessels recruits an inflammatory response with expression of cytokines and growth factors, upregulation of eNOS in vascular endothelial cells, and expression of iNOS in both vessels and cardiac myocytes. Since NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with N(G)-nitro-L-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor, 1400W, caused a 21±5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MVO2). The results suggest that NO produced by iNOS inhibits MVO2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MVO2. Thus, the coordinated expression of iNOS to restrain MVO2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship in the collateralized region.
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Simplified Quantitative Glycomics Using the Stable Isotope Label Girards Reagent P by Electrospray Ionization Mass Spectrometry.
J. Proteome Res.
PUBLISHED: 12-02-2013
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Fast, sensitive, and simple methods for quantitative analysis of disparities in glycan expression between different biological samples are essential for studies of protein glycosylation patterns (glycomics) and the search for disease glycan biomarkers. Relative quantitation of glycans based on stable isotope labeling combined with mass spectrometric detection represents an emerging and promising technique. However, this technique is undermined by the complexity of mass spectra of isotope-labeled glycans caused by the presence of multiple metal ion adduct signals, which result in a decrease of detection sensitivity and an increase of difficulties in data interpretation. Herein we report a simplified quantitative glycomics strategy, which features nonreductive isotopic labeling of reducing glycans with either nondeuterated (d0-) or deuterated (d5-) Girards reagent P (GP) without salts introduced and simplified mass spectrometric profiles of d0- and d5-GP derivatives of neutral glycans as molecular ions without complex metal ion adducts, allowing rapid and sensitive quantitative comparison between different glycan samples. We have obtained optimized GP-labeling conditions and good quantitation linearity, reproducibility, and accuracy of data by the method. Its excellent applicability was validated by comparatively quantitative analysis of the neutral N-glycans released from bovine and porcine immunoglobulin G as well as of those from mouse and rat sera. Additionally, we have revealed the potential of this strategy for the high-sensitivity analysis of sialylated glycans as GP derivatives, which involves neutralization of the carboxyl group of sialic acid by chemical derivatization.
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[Efficacies of bone-marrow-derived mononuclear cells with a hydroxylapatite composite in the treatment of osteonecrosis of the femoral head].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-29-2013
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To evaluate the efficacies of core decompression and implantation of concentrated autologous bone marrow containing mononuclear cells (BMMCs) with porous hydroxylapatite composite in the treatment of osteonecrosis of the femoral head.
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[Types and risk factors of arrhythmia on young patients with acute coronary syndrome in Henan province].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-29-2013
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The types and risk factors of arrhythmia were analyzed on acute coronary syndrome (ACS) patients under the age of 44 years who were hospitalized in Henan province between September 2009 to June 2012.
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Rates of diagnostic transition and cognitive change at 18-month follow-up among 1,112 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL).
Int Psychogeriatr
PUBLISHED: 11-20-2013
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ABSTRACT Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimers disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not. Methods: Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. Results: The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinsons disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. Conclusion: There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.
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Alkene Oxyalkylation Enabled by Merging Rhenium Catalysis with Hypervalent Iodine(III) Reagents via Decarboxylation.
J. Am. Chem. Soc.
PUBLISHED: 11-20-2013
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Rhenium-catalyzed oxyalkylation of alkenes is described, where hypervalent iodine(III) reagents derived from widely occurring aliphatic carboxylic acids were used as, for the first time, not only an oxygenation source but also an alkylation source via decarboxylation. The reaction also features a wide substrate scope, totally regiospecific difunctionalization, mild reaction conditions, and ready availability of both substrates. Mechanistic studies revealed a decarboxylation/radical-addition/cation-trapping cascade operating in the reaction.
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[Development of full-quantified HPLC fingerprint for quality evaluation of ophiopogonis radix of sichuan].
Zhong Yao Cai
PUBLISHED: 11-14-2013
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To establish HPLC fingerprint of Ophiopogonis Radix of Sichuan and simultaneously determine two homoisoflavonoids (methylophiopogonanones A and B).
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A novel functional class 2 integron in clinical Proteus mirabilis isolates.
J. Antimicrob. Chemother.
PUBLISHED: 11-13-2013
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To describe a novel functional class 2 integron that was found in clinical Proteus mirabilis isolates.
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Serotonin acts as a novel regulator of interleukin-6 secretion in osteocytes through the activation of the 5-HT2B receptor and the ERK1/2 signalling pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-24-2013
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Interleukin-6 (IL-6) is a potent stimulator of osteoclastic bone resorption. Osteocyte secretion of IL-6 plays an important role in bone metabolism. Serotonin (5-HT) has recently been reported to regulate bone metabolism. The aim of this study was to evaluate the effect of serotonin on osteocyte expression of IL-6. The requirement for the 5-HT receptor(s) and the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) in serotonin-induced IL-6 synthesis were examined. In this study, real-time PCR and ELISA were used to analyse IL-6 gene and protein expression in serotonin-stimulated MLO-Y4 cells. ERK1/2 pathway activation was determined by Western blot. We found that serotonin significantly activated the ERK1/2 pathway and induced IL-6 mRNA expression and protein synthesis in cultured MLO-Y4 cells. However, these effects were abolished by pre-treatment of MLO-Y4 cells with a 5-HT2B receptor antagonist, RS127445 or the ERK1/2 inhibitor, PD98059. Our results indicate that serotonin stimulates osteocyte secretion of IL-6 and that this effect is associated with activation of 5-HT2B receptor and the ERK1/2 pathway. These findings provide support for a role of serotonin in bone metabolism by indicating serotonin regulates bone remodelling by mediating an inflammatory cytokine.
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The Contribution of Cdc2 in Rotenone-Induced G2/M Arrest and Caspase-3-Dependent Apoptosis.
J. Mol. Neurosci.
PUBLISHED: 10-01-2013
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Neuronal cell cycle reentry maintained in a G2-like state before cell death, has been confirmed in dopaminergic neurons of patients with Parkinsons disease (PD). Caspase-3 is a final effector in apoptotic dopaminergic neurons in patients. The association of aberrant G2/M regulation with caspase-3 dependent apoptosis remains to be elucidated. Cell division cycle protein 2 (Cdc2) is a key player in G2/M transition in mitotic cells. Although the deregulation of Cdc2 correlated with the control of apoptosis in neurons, the molecular pathway by which Cdc2 involves in apoptosis is not clear. In a rotenone-based cell model of PD, we demonstrated that rotenone arrested cell cycle at G2/M phase and activated caspase-3 both in cytoplasm and nucleus. The decreased activity of Cdc2 by roscovitine or rotenone enhanced G2/M arrest. The increased cells in G2/M arrest by rotenone upregulated the expression of Cdc2. Suppression of Cdc2 expression downregulated cleaved caspase-3/9 and delayed cell apoptosis. Used together, the upregulation of Cdc2 contributes to rotenone-induced caspase-3/9-dependent apoptosis, which is associated with the enhancement of G2/M arrest. Our results suggest the deregulation of Cdc2 as a transition between cell cycle arrest and cell death.
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Identification of natural splice variants of SAMHD1 in virus-infected HCC.
Oncol. Rep.
PUBLISHED: 09-24-2013
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It has been previously shown that the sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1) can act as a retroviral restriction factor by inhibiting HIV?1 infection, but whether it has any roles in cancer is still unclear. In the present study, we identified several SAMHD1 splice variants naturally occurring in liver cancer and investigated their roles in regulating drug susceptibility. SAMHD1 variants were identified by sequencing. RT-PCR and western blot analysis were performed to verify the expression level of the polymorphisms. Cell cycle analysis was carried out using flow cytometry, and data were analyzed using Multicycle software. Several deletions of SAMHD1 were identified in both the patients and the healthy controls with no significant difference in respective frequencies, while an insertion in the exon4 occurred at a higher frequency in HBV- and HCV-infected patients (36.4 and 30%, respectively) when compared to the control groups. Following cisplatin treatment and cell cycle analysis, SAMHD1 variants showed different activities in increasing the susceptibility to chemotherapy drugs. The insertion of exon4 correlated with the occurrence of virus infection in the HCC patients. In conclusion, analysis of the different activities of SAMHD1 splice variants in regulating drug sensitivity implied that the exon4 insertion might act as an indicator of the occurrence of liver cancer.
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Learning by aggregating experts and filtering novices: a solution to crowdsourcing problems in bioinformatics.
BMC Bioinformatics
PUBLISHED: 09-24-2013
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In many biomedical applications, there is a need for developing classification models based on noisy annotations. Recently, various methods addressed this scenario by relaying on unreliable annotations obtained from multiple sources.
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Endothelial Insulin-Like Growth Factor-1 Modulates Proliferation and Phenotype of Smooth Muscle Cells Induced by Low Shear Stress.
Ann Biomed Eng
PUBLISHED: 08-31-2013
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Endothelial cells (ECs) are directly exposed to shear stress and modulate the neighboring vascular smooth muscle cells (VSMCs), which plays important roles in vascular remodeling during atherosclerosis. Our previous research revealed that insulin-like growth factors (IGFs) might participate in low shear stress (LowSS) induced vascular remodeling, which remains to be elucidated. Using EC/VSMC co-cultured parallel-plate flow chamber, LowSS (5 dyn/cm(2)) was applied and normal shear stress (NSS, 15 dyn/cm(2)) was used as control. LowSS induced IGF-1 secretion from ECs, which subsequently phosphorylated IGF-1 receptor (IGF-1R) on co-cultured VSMCs, then increased Akt phosphorylation and Sirt2 expression. Decreasing IGF-1 in ECs by RNA interference (RNAi) reversed these effects on VSMCs. Exogenous IGF-1 increased IGF-1R and Akt phosphorylation, Sirt2 expression, and proliferation of VSMCs, and induced VSMCs towards synthetic phenotype. PI3 K/Akt specific inhibitor wortmannin decreased Sirt2 expression, proliferation, and synthetic phenotype transformation of VSMCs, but had no effect on IGF-1R. Sirt2 RNAi repressed VSMC proliferation and phenotypic transformation, but had no effect on IGF-1R and Akt. Taken together, LowSS induces the secretion of IGF-1 from ECs, which subsequently paracrine influences the co-cultured VSMCs via IGF-1R and Akt phosphorylation, and Sirt2 expression, then results in the proliferation and synthetic phenotype transformation.
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Stereoselective Degradation of Chiral Fungicide Myclobutanil in Rat Liver Microsomes.
Chirality
PUBLISHED: 08-07-2013
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Myclobutanil, (RS)-2-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-ylmethyl)hexanenitrile is a broad-spectrum systemic triazole fungicide which consists of a pair of enantiomers. The stereoselective degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high-performance liquid chromatography (HPLC) with a cellulose-tris-(3,5-dimethyl-phenylcarbamate)-based chiral stationary phase (CDMPC-CSP) under reversed phase condition. The t1/2 of (+)-myclobutanil is 8.49?min, while the t1/2 of (-)-myclobutanil is 96.27?min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was stereoselective and the degradation rate of (+)-myclobutanil was much faster than (-)-myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The Vmax of (+)-myclobutanil was about 4-fold of (-)-myclobutanil and the CLint of (+)-myclobutanil was three times as much as (-)-myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological risk assessment for myclobutanil and may improve human health. Chirality 00:000-000, 2013. © 2013 Wiley Periodicals, Inc.
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