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Find video protocols related to scientific articles indexed in Pubmed.
Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study.
Blood Coagul. Fibrinolysis
PUBLISHED: 11-13-2014
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Previous studies showed that selenoprotein S (SELS) was associated with a range of inflammatory markers, and its gene expression was influenced by a polymorphism in the promoter region. The genetic basis of the ischemic stroke has now been largely determined, so the aim of the study was to examine the role of SELS genetic variants in the ischemic stroke risk in a Chinese population. We conducted a case-control study with 239 ischemic stroke patients and 240 controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed for association with the risk of ischemic stroke in the Chinese Han population. No evidence of ischemic stroke association was observed with the SNP rs34713741. Interestingly, the strongest evidence showed that SELS SNP rs4965814 was associated with ischemic stroke (P?
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Bioactive constituents of oleanane-type triterpene saponins from the roots of Glycyrrhiza glabra.
J Asian Nat Prod Res
PUBLISHED: 10-08-2014
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Three new oleanane-type triterpene saponins, namely licorice-saponin M3 (1), licorice-saponin N4 (2), and licorice-saponin O4 (3), an artificial product (4), as well as five known triterpene glucuronides (5-9), were isolated from the roots of Glycyrrhiza glabra L. Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry, and by comparison with spectroscopic data reported in the literature. The inhibitory effects of the selected compounds on neuraminidase were evaluated, and the preliminary structure-activity relationship was also predicted.
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ICAM-1 as a molecular target for triple negative breast cancer.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-29-2014
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Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAM-IONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.
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Psychrophilins E-H and Versicotide C, Cyclic Peptides from the Marine-Derived Fungus Aspergillus versicolor ZLN-60.
J. Nat. Prod.
PUBLISHED: 09-23-2014
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Four new cyclic peptides, psychrophilins E-H (1-4), possessing a rare amide linkage between the carboxylic acid in anthranilic acid (ATA) and the nitrogen from an indole moiety, along with a new ATA-containing hexapeptide, versicotide C (5), were obtained from the culture of the marine-derived fungus Aspergillus versicolor ZLN-60. The structures, including absolute configurations, were elucidated by a combination of HRESIMS, NMR, X-ray crystallography, TDDFT ECD calculations, and Marfey's method. Versicotide C (5) is the first natural cyclic hexapeptide containing two anthranilic acids. Compounds 1-5 were not cytotoxic, and compound 3 showed potent lipid-lowering effects.
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[The synergistic effect of FGF-21 and insulin on regulating glucose metabolism and its mechanism].
Yao Xue Xue Bao
PUBLISHED: 09-20-2014
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Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.
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cDNA-AFLP analysis reveals the adaptive responses of citrus to long-term boron-toxicity.
BMC Plant Biol.
PUBLISHED: 09-13-2014
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BackgroundBoron (B)-toxicity is an important disorder in agricultural regions across the world. Seedlings of `Sour pummelo¿ (Citrus grandis) and `Xuegan¿ (Citrus sinensis) were fertigated every other day until drip with 10 ¿M (control) or 400 ¿M (B-toxic) H3BO3 in a complete nutrient solution for 15 weeks. The aims of this study were to elucidate the adaptive mechanisms of citrus plants to B-toxicity and to identify B-tolerant genes.ResultsB-toxicity-induced changes in seedlings growth, leaf CO2 assimilation, pigments, total soluble protein, malondialdehyde (MDA) and phosphorus were less pronounced in C. sinensis than in C. grandis. B concentration was higher in B-toxic C. sinensis leaves than in B-toxic C. grandis ones. Here we successfully used cDNA-AFLP to isolate 67 up-regulated and 65 down-regulated transcript-derived fragments (TDFs) from B-toxic C. grandis leaves, whilst only 31 up-regulated and 37 down-regulated TDFs from B-toxic C. sinensis ones, demonstrating that gene expression is less affected in B-toxic C. sinensis leaves than in B-toxic C. grandis ones. These differentially expressed TDFs were related to signal transduction, carbohydrate and energy metabolism, nucleic acid metabolism, protein and amino acid metabolism, lipid metabolism, cell wall and cytoskeleton modification, stress responses and cell transport. The higher B-tolerance of C. sinensis might be related to the findings that B-toxic C. sinensis leaves had higher expression levels of genes involved in photosynthesis, which might contribute to the higher photosyntheis and light utilization and less excess light energy, and in reactive oxygen species (ROS) scavenging compared to B-toxic C. grandis leaves, thus preventing them from photo-oxidative damage. In addition, B-toxicity-induced alteration in the expression levels of genes encoding inorganic pyrophosphatase 1, AT4G01850 and methionine synthase differed between the two species, which might play a role in the B-tolerance of C. sinensis.Conclusions C. sinensis leaves could tolerate higher level of B than C. grandis ones, thus improving the B-tolerance of C. sinensis plants. Our findings reveal some novel mechanisms on the tolerance of plants to B-toxicity at the gene expression level.
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[Effect of light quality on growth, photosynthesis and effective components of Panax notoginseng].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-11-2014
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In order to discover light quality's effects on growth, photosynthesis and effective components content of Panax notoginseng, a pot experiment using 7 light qualities (red, orange, yellow, green, cyan, violet, and blue) was conducted. The growth, photosynthesis and content change of effective components were measured during plant growth. The results showed that light qualities had significant effect on plant growth, red light increased the plant height, while cyan, yellow, violet, and blue lights promoted accumulation of biomass underground, blue and yellow lights increased the photosynthesis, cyan light increased accumulation of ginsenoside Rd, yellow and cyan lights increased total effective components of individual plant.
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Chlorogenic acid protects against atherosclerosis in ApoE-/- mice and promotes cholesterol efflux from RAW264.7 macrophages.
PLoS ONE
PUBLISHED: 09-04-2014
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Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE(-/-) mice and its potential mechanism. ApoE(-/-) mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPAR?, LXR?, ABCA1 and ABCG1 as well as the transcriptional activity of PPAR?. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE(-/-) mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA.
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Curcumin promotes KLF5 proteasome degradation through downregulating YAP/TAZ in bladder cancer cells.
Int J Mol Sci
PUBLISHED: 08-28-2014
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KLF5 (Krüppel-like factor 5) plays critical roles in normal and cancer cell proliferation through modulating cell cycle progression. In this study, we demonstrated that curcumin targeted KLF5 by promoting its proteasome degradation, but not by inhibiting its transcription in bladder cancer cells. We also demonstrated that lentivirus-based knockdown of KLF5 inhibited cancer cell growth, while over-expression of a Flag-tagged KLF5 could partially reverse the effects of curcumin on cell growth and cyclin D1 expression. Furthermore, we found that curcumin could down-regulate the expression of Hippo pathway effectors, YAP and TAZ, which have been reported to protect KLF5 protein from degradation. Indeed, knockdown of YAP by small interfering RNA caused the attenuation of KLF5 protein, but not KLF5 mRNA, which was reversed by co-incubation with proteasome inhibitor. A xenograft assay in nude mice finally proved the potent inhibitory effects of curcumin on tumor growth and the pro-proliferative YAP/TAZ/KLF5/cyclin D1 axis. Thus, our data indicates that curcumin promotes KLF5 proteasome-dependent degradation through targeting YAP/TAZ in bladder cancer cells and also suggests the therapeutic potential of curcumin in the treatment of bladder cancer.
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A crystal structure-guided rational design switching non-carbohydrate inhibitors' specificity between two ?-GlcNAcase homologs.
Sci Rep
PUBLISHED: 08-26-2014
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Selective inhibition of function-specific ?-GlcNAcase has great potential in terms of drug design and biological research. The symmetrical bis-naphthalimide M-31850 was previously obtained by screening for specificity against human glycoconjugate-lytic ?-GlcNAcase. Using protein-ligand co-crystallization and molecular docking, we designed an unsymmetrical dyad of naphthalimide and thiadiazole, Q2, that changes naphthalimide specificity from against a human glycoconjugate-lytic ?-GlcNAcase to against insect and bacterial chitinolytic ?-GlcNAcases. The crystallographic and in silico studies reveal that the naphthalimide ring can be utilized to bind different parts of these enzyme homologs, providing a new starting point to design specific inhibitors. Moreover, Q2-induced closure of the substrate binding pocket is the structural basis for its 13-fold increment in inhibitory potency. Q2 is the first non-carbohydrate inhibitor against chitinolytic ?-GlcNAcases. This study provides a useful example of structure-based rationally designed inhibitors as potential pharmaceuticals or pesticides.
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Correlation of Hippocampal Volume and Cognitive Performances in Patients with Either Mild Cognitive Impairment or Alzheimer's disease.
CNS Neurosci Ther
PUBLISHED: 08-21-2014
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To evaluate hippocampal volume changes and neuropsychological performances in patients with either amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD).
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Up-regulated expression of PD-1 and its ligands during acute Classical Swine Fever virus infection in swine.
Res. Vet. Sci.
PUBLISHED: 08-19-2014
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In order to investigate the relationship between the PD-1 pathway and impairment of immune responses with the CSFV infection, the mRNA expression of PD-1 and its ligands were evaluated by quantitative polymerase chain reaction (qPCR) during artificial CSFV infection. Simultaneously, expression of IL-2 and IL-10 mRNA were detected. The T cell proliferation and CSFV load in plasma were also measured. Results showed that the expression of PD-1 and its ligands mRNA were significantly increased (p?
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Experimental study on the dynamics of polarized strong optical injection in 1550 nm VCSELs.
Opt Lett
PUBLISHED: 08-15-2014
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We have experimentally analyzed the dynamics of polarized strong optical injection in 1550 nm vertical-cavity surface-emitting lasers (VCSELs). The locking ranges of optical injection-locked (OIL) VCSELs are experimentally measured in different states of polarized strong optical injection. Based on our novel ellipse model, the influence of the polarization state of strong injection light is quantitatively studied for the first time.
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AKR1C3 overexpression mediates methotrexate resistance in choriocarcinoma cells.
Int J Med Sci
PUBLISHED: 08-13-2014
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Chemotherapy is typically used to treat choriocarcinoma, but a small proportion of tumors develop resistance to chemotherapy. Similarly, methotrexate (MTX) is a first-line chemotherapy used to treat choriocarcinoma; although ~30% of patients are drug-resistant for MTX mono-therapy. Thus, we sought to elucidate the mechanism of chemotherapeutic-resistance of MTX.
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Effects of different types of N deposition on the fungal decomposition activities of temperate forest soils.
Sci. Total Environ.
PUBLISHED: 08-12-2014
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Nitrogen (N) deposition significantly affects soil microbial activities and litter decomposition processes in forest ecosystems. However, the changes in soil fungi during litter decomposition remain unclear. In this study, ammonium nitrate was selected as inorganic N (IN), whereas urea and glycine were selected as organic N (ON). N fertilizer with different IN-to-ON ratios (1:4, 2:3, 3:2, 4:1, and 5:0) was mixed in equal amounts and then added to temperate forest soils. Half of each treatment was simultaneously added with streptomycin to inhibit soil bacteria. The activities of enzymes involved in litter decomposition (invertase, ?-glucosidase, cellulase, polyphenol oxidase, and phosphatase) were assayed after a three-year field experiment. The results showed that enzymatic activities were inhibited by IN addition but accelerated by ON addition in the non-antibiotic addition treatments. An increase in ON in the mixed N fertilizer also shifted enzymatic activities from N inhibition to N stimulation. Similarly, in the antibiotic addition treatments, fungal activities revealed the same trends, but they were seriously inhibited by IN and significantly accelerated by ON. These results indicated that soil fungi were more sensitive to N deposition, particularly to ON. A large amount of ON may convert soil microbial communities into a fungi-dominated system. However, excessive ON deposition (20% IN+80% ON) caused N saturation and repressed fungal activities. These results suggested that soil fungi were sensitive to N type and that different IN-to-ON ratios may induce diverse ecological effects on soil fungi.
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Intermittently administered parathyroid hormone [1-34] promotes tendon-bone healing in a rat model.
Int J Mol Sci
PUBLISHED: 08-11-2014
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The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]) promotes tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 ?g PTH[1-34]/kg subcutaneously were given to the PTH group rats (n=10) for four weeks, and the controls (n=10) received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1-34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R) and osteocalcin were determined. Administration of PTH[1-34] significantly increased serum levels of calcium, alkaline phosphatase (AP), osteocalcin and tartrate-resistant acid phosphatase (TRAP). The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1-34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1-34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction.
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[Myeloid-derived Gr-1? CD11b? suppressor cells are involved in immunoregulation of experimental autoimmune encephalomyelitis].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 08-11-2014
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To explore the change in the number and role of Gr-1? CD11b? myeloid-derived suppressor cells (MDSCs) in experimental autoimmune encephalomyelitis (EAE).
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Lipid-lowering effects of farnesylquinone and related analogues from the marine-derived Streptomyces nitrosporeus.
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-31-2014
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Bioassay-guided fractionation of the fermentation broth of Arctic Streptomyces nitrosporeus YBH10-5 resulted in the isolation of seven new compounds named nitrosporeunols A-G (1-7), together with seven known analogues (8-14). Their structures were determined based on extensive spectroscopic analysis. Compounds 1-14 were evaluated for the lowering lipid effects, while two compounds (10 and 12) remarkably decreased lipid levels including total cholesterol (TC) and triglycerides (TG) in HepG2 cells. Quantitative realtime PCR and Western blot indicated that farnesylquinone (12) increased the expression of the key proteins including peroxisome proliferator-activated receptor-? (PPAR?), peroxisome proliferator-activated receptor-?, and coactivator 1? (PGC-1?), as well as their downstream genes carnitine palmitoyltransterase-1 (CPT-1), acyl-coenzyme A oxidase 1 (ACOX), malonyl CoA decarboxylase 1 (MCD1), pyruvate dehydrogenase kinase 4 (PDK4), and cholesterol 7? -hydroxylase (CYP7A1). Luciferase assay showed that 12 increased the transcriptional activity of PPAR?, while its lipid-lowering effect was abolished by PPAR? inhibitor, MK886, in HepG2 cells. These findings suggested that 12 is a potent lipid-lowering agent which may decrease lipid levels through upregulation of PPAR? pathway.
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Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.
ACS Appl Mater Interfaces
PUBLISHED: 07-30-2014
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Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.
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Cartilage oligomeric matrix protein gene multilayers inhibit osteogenic differentiation and promote chondrogenic differentiation of mesenchymal stem cells.
Int J Mol Sci
PUBLISHED: 07-18-2014
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There are still many challenges to acquire the optimal integration of biomedical materials with the surrounding tissues. Gene coatings on the surface of biomaterials may offer an effective approach to solve the problem. In order to investigate the gene multilayers mediated differentiation of mesenchymal stem cells (MSCs), gene functionalized films of hyaluronic acid (HA) and lipid-DNA complex (LDc) encoding cartilage oligomeric matrix protein (COMP) were constructed in this study via the layer-by-layer self-assembly technique. Characterizations of the HA/DNA multilayered films indicated the successful build-up process. Cells could be directly transfected by gene films and a higher expression could be obtained with the increasing bilayer number. The multilayered films were stable for a long period and DNA could be easily released in an enzymatic condition. Real-time polymerase chain reaction (RT-PCR) assay presented significantly higher (p < 0.01) COMP expression of MSCs cultured with HA/COMP multilayered films. Compared with control groups, the osteogenic gene expression levels of MSCs with HA/COMP multilayered films were down-regulated while the chondrogenic gene expression levels were up-regulated. Similarly, the alkaline phosphatase (ALP) staining and Alizarin red S staining of MSCs with HA/COMP films were weakened while the alcian blue staining was enhanced. These results demonstrated that HA/COMP multilayered films could inhibit osteogenic differentiation and promote chondrogenic differentiation of MSCs, which might provide new insight for physiological ligament-bone healing.
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New occurrence of Sinovipera sichuanensis in Guizhou.
Zool. Res.
PUBLISHED: 07-15-2014
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Three Asian green pit vipers were collected in August 2013 during a field trip in Fanjin Mt. National Conservation Area, Guizhou. These specimens were identified as Sinovipera sichuanensis, based on subsequent examination and comparison. This is a new record of the genus Sinovipera and S. sichuanensis in Guizhou, and the first time that male specimens have been collected in the field.
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[Analysis of multicomponent drug metabolism used in clinical pharmacy research of traditional Chinese medicine].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-12-2014
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Multicomponent drug metabolism can be defined as a research area that, rather than pharmacokinetics and pharmacodynamics, is a concerted dynamic metabolic variation of one component in several other compounds circumstance with the interaction of transport protein and drug metabolizing enzymes, and the study of the dynamic course of multiple components must be simultaneously determined. By the use of multicomponent drug metabolism in the clinical pharmacy research of traditional Chinese medicine (TCM), it can become a useful tool with the integration of the overall dialectical method and the concrete molecular approach.
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Testosterone regulates keratin 33B expression in rat penis growth through androgen receptor signaling.
Asian J. Androl.
PUBLISHED: 07-05-2014
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Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR) protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b). Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.
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Therapeutic effects of laparoscopic splenectomy and esophagogastric devascularization on liver cirrhosis and portal hypertension in 204 cases.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 06-24-2014
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To investigate the effects and technical points of laparoscopic splenectomy and esophagogastric devascularization (LS+ED) for portal hypertension (PH) due to liver cirrhosis.
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Metformin sensitizes prostate cancer cells to radiation through EGFR/p-DNA-PKCS in vitro and in vivo.
Radiat. Res.
PUBLISHED: 05-20-2014
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Although neo-adjuvant radiotherapy is generally successful in treatment of advanced prostate cancer, radioresistance is still a major therapeutic problem in many patients. In the current study, we investigated the effects of metformin (1,1-dimethylbiguanide hydrochloride), a widely used antidiabetic drug, on tumor cell radiosensitivity in prostate cancer. Through clonogenic survival assays, we found that metformin treatment enhanced radiosensitivity of prostate cancer cells with a dose enhancement factor. Moreover, irradiation of subcutaneous C4-2 tumors in mice treated with metformin resulted in an increase in radiation-induced tumor growth delay (17.3 days to 29.5 days, P < 0.01), which indicates that the tumor radiosensitivity increased by metformin in vivo. We also measured the sublethal damage repair and analyzed double-strand breaks (DSBs) in X-irradiated cells. ?-H2AX, as an indicator of DSBs, had significantly more foci per cell in the group treated with metformin and radiation compared to groups treated with metformin or irradiation, respectively. Moreover, mice with subcutaneous tumor implants lived longer after a combined treatment of metformin and radiation. In addition, the reduced phosphorylation of DNA-PKcs caused by EGFR/PI3K/Akt down-regulation is essential for metformin to induce radiosensitivity in prostate cancer cells. Our results indicate that metformin enhances prostate cancer cell radiosensitivity in vitro and in vivo. Exposure to metformin before radiation therapy could be a beneficial option for the treatment of prostate cancer.
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Ab initio structure determination of interlayer expanded zeolites by single crystal rotation electron diffraction.
Dalton Trans
PUBLISHED: 05-09-2014
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Layered solids often form thin plate-like crystals that are too small to be studied by single-crystal X-ray diffraction. Although powder X-ray diffraction (PXRD) is the conventional method for studying such solids, it has limitations because of peak broadening and peak overlapping. We have recently developed a software-based rotation electron diffraction (RED) method for automated collection and processing of 3D electron diffraction data. Here we demonstrate the ab initio structure determination of two interlayer expanded zeolites, the microporous silicates COE-3 and COE-4 (COE-n stands for International Network of Centers of Excellence-n), from submicron-sized crystals by the RED method. COE-3 and COE-4 are built of ferrierite-type layers pillared by (-O-Si(CH3)2-O-) and (-O-Si(OH)2-O-) linker groups, respectively. The structures contain 2D intersecting 10-ring channels running parallel to the ferrierite layers. Because both COE-3 and COE-4 are electron-beam sensitive, a combination of RED datasets from 2 to 3 different crystals was needed for the structure solution and subsequent structure refinement. The structures were further refined by Rietveld refinement against the PXRD data. The structure models obtained from RED and PXRD were compared.
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Risk of cerebral arteriovenous malformation rupture during pregnancy and puerperium.
Neurology
PUBLISHED: 04-23-2014
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To determine whether the risk of arteriovenous malformation (AVM) rupture is increased during pregnancy and puerperium.
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Sesamin enhances cholesterol efflux in RAW264.7 macrophages.
Molecules
PUBLISHED: 04-14-2014
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Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 ?M) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPAR?, LXR?, and ABCG1, and increased the transcriptional activity of PPAR?. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPAR?. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPAR?-LXR?-ABCG1 pathway.
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Punctaporonins H-M: caryophyllene-type sesquiterpenoids from the sponge-associated fungus Hansfordia sinuosae.
Mar Drugs
PUBLISHED: 04-11-2014
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Six new caryophyllene-based sesquiterpenoids named punctaporonins H-M (1-6), together with punctaporonin B (7) and humulane (8) were isolated from the fermentation broth of the sponge-derived fungus Hansfordia sinuosae. Their structures were determined by the extensive HRESIMS and NMR spectroscopic analysis, including the X-ray crystallographic data for the assignment of the absolute configurations of punctaporonins H-I (1-2). The isolated compounds were evaluated for antihyperlipidemic, cytotoxic and antimicrobial activities, and punctaporonin K (4) exhibited potent effects to reduce the triglycerides and total cholesterol in the intracellular levels.
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Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.
Anticancer Drugs
PUBLISHED: 04-10-2014
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Metformin, an oral antidiabetic agent, has been reported to potentiate chemotherapeutic-induced cytotoxicity. In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells. Metformin alone did not induce apoptosis, but markedly potentiated TRAIL-induced apoptosis in 253J and RT4 bladder cancer cells. To elucidate the underlying mechanism, we examined the modulatory effects of metformin on the key components of the TRAIL signaling pathway and found that metformin did not alter the expression levels of death receptor 4 (DR4) and death receptor 5 (DR5), but significantly reduced the cellular Fas-associated death domain (FADD)-like interleukin-1?-converting enzyme (FLICE) inhibitory protein (c-FLIP) levels, contributing toward the sensitization to TRAIL. Further experiments showed that metformin did not affect the mRNA level, proteasomal degradation, and protein stability of c-FLIPL. However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway. In addition, AMP-activated protein kinase (AMPK) inhibitor compound C did not prevent the inhibitory effects of metformin on the mTOR/S6K1 pathway and metformin-mediated sensitization to TRAIL. Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.
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Functional study of TREK-1 potassium channels during rat heart development and cardiac ischemia using RNAi techniques.
J. Cardiovasc. Pharmacol.
PUBLISHED: 04-08-2014
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To explore the physiological and pathological significance of the 2-pore domain potassium channel TWIK-related K(+) (TREK)-1 in rat heart, its expression and role during heart development and cardiac ischemia were investigated. In the former study, the ventricles of Sprague Dawley rats were collected from embryo day 19 to postnatal 18 months and examined for mRNA and protein expression of TREK-1. It was found that both increased during development, reached a maximum at postnatal day 28, and remained higher at postnatal day 3 through to postnatal 18 months. In the latter study, protein expression of TREK-1 was examined after initiation of acute heart ischemia by ligation of the left anterior descending coronary artery. TREK-1 expression was found to be increased in the endocardium but unchanged in the epicardium. In primary cultured rat neonatal ventricular myocytes subjected to hypoxia (oxygen-glucose deprivation), TREK-1 expression was increased. In cultured neonatal cardiomyocytes, silencing of the TREK-1 gene by lentivirus delivery of the short-hairpin RNAs, L-sh-492 and L-sh-605, was found to promote their viability and number. In addition, both short-hairpin RNA provided protection against hypoxia-induced injury to cardiomyocytes in vitro. These results suggest that TREK-1 plays an important role in neonatal rat heart development and downregulation of TREK-1 may provide protection against ischemic injury. It seems that TREK-1 is a potential drug target for treatment of acute heart ischemia.
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The caffeoylquinic acid-rich Pandanus tectorius fruit extract increases insulin sensitivity and regulates hepatic glucose and lipid metabolism in diabetic db/db mice.
J. Nutr. Biochem.
PUBLISHED: 03-18-2014
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Caffeoylquinic acids (CQAs) are widely distributed in various foods. While some CQAs have been shown to possess antihyperglycemic activities, whether it is beneficial for diabetes patients to ingest CQA-rich foods has still to be known. In this work, the antihyperglycemic and antihyperlipidemic effects of CQA-rich Pandanus tectorius fruit extract (PTF) was investigated in diabetic db/db mice. Treatment with PTF (200 mg/kg) significantly decreased body weight and fasting glucose level, alleviated hyperinsulinism and hyperlipidemia and declined glucose area under the curve in oral glucose tolerance test and insulin tolerance test. The elevated levels of serum proinflammatory cytokines and islet hypertrophy in db/db mice were remarkably attenuated by PTF treatment. Biochemical analysis showed that administration of PTF significantly stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and Akt substract of 160 kDa (AS160), and enhanced the expression and translocation of glucose transporter type 4 (GLUT4) in skeletal muscles. It also increased the activity of hexokinase, decreased the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase and switched the transcription of several key lipid metabolic genes in the liver, which, in turn, improved hepatic glucose and lipid profiles as determined by nuclear magnetic resonance-based metabolomics. Overall, the CQA-rich PTF is beneficial for the treatment of diabetes. It may alleviate hyperglycemia and dyslipidemia via activation of AMPK-AS160-GLUT4 pathway in skeletal muscles and inhibition of gluconeogenesis and lipogenesis in the liver.
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Prevalence and associated factors of induced abortion among rural married women: A cross-sectional survey in Anhui, China.
J. Obstet. Gynaecol. Res.
PUBLISHED: 03-17-2014
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This study aims to assess the prevalence of and factors associated with induced abortion among married women in rural areas of Anhui Province, China.
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Hypertonic saline in the traumatic hypovolemic shock: meta-analysis.
J. Surg. Res.
PUBLISHED: 03-16-2014
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A wealth of evidence from animal experiments has indicated that hypertonic saline (HS) maybe a better choice for fluid resuscitation in traumatic hypovolemic shock in comparison with conventional isotonic saline. However, the results of several clinical trials raised controversies on the superiority of fluid resuscitation with HS. This meta-analysis was performed to better understand the efficacy of HS in patients with traumatic hypovolemic shock comparing with isotonic saline.
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Magneto-fluorescent core-shell supernanoparticles.
Nat Commun
PUBLISHED: 03-12-2014
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Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.
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[Acyldepsipeptide 1 induces apoptosis in renal cancer cells by down-regulation of Gli and Bcl-2 via SHH pathway].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 03-11-2014
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To investigate the effects of acyldepsipeptide 1 (ADEP1) on renal cancer cell apoptosis and on the expressions of SHH signaling pathway related protein Gli-1 and Bcl-2.
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Low-noise and broadband optical frequency comb generation based on an optoelectronic oscillator.
Opt Lett
PUBLISHED: 02-25-2014
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A novel scheme to generate broadband high-repetition-rate optical frequency combs and low phase noise microwave signals simultaneously is proposed and experimentally demonstrated. By incorporating an optical frequency comb generator in an optoelectronic oscillator loop, more than 200 lines are generated for a 25 GHz optical frequency comb, and the single-sideband phase noise is as low as -122??dBc/Hz at 10 kHz offset for the 25 GHz microwave signal. 10 and 20 GHz optical frequency combs and microwave signals are also generated. Unlike the microwave frequency synthesizer, the phase noise of the microwave signals generated by this new scheme is frequency independent.
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Different types of nitrogen deposition show variable effects on the soil carbon cycle process of temperate forests.
Glob Chang Biol
PUBLISHED: 02-14-2014
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Nitrogen (N) deposition significantly affects the soil carbon (C) cycle process of forests. However, the influence of different types of N on it still remained unclear. In this work, ammonium nitrate was selected as an inorganic N (IN) source, while urea and glycine were chosen as organic N (ON) sources. Different ratios of IN to ON (1 : 4, 2 : 3, 3 : 2, 4 : 1, and 5 : 0) were mixed with equal total amounts and then used to fertilize temperate forest soils for 2 years. Results showed that IN deposition inhibited soil C cycle processes, such as soil respiration, soil organic C decomposition, and enzymatic activities, and induced the accumulation of recalcitrant organic C. By contrast, ON deposition promoted these processes. Addition of ON also resulted in accelerated transformation of recalcitrant compounds into labile compounds and increased CO2 efflux. Meanwhile, greater ON deposition may convert C sequestration in forest soils into C source. These results indicated the importance of the IN to ON ratio in controlling the soil C cycle, which can consequently change the ecological effect of N deposition.
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[Clinicopathologic characteristics of basal cell carcinoma of the prostate: analysis of 5 cases and review of the literature].
Zhonghua Nan Ke Xue
PUBLISHED: 02-14-2014
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To investigate the histogenesis, clinicopathologic characteristics, pathologic diagnosis, differential diagnosis, treatment and prognosis of basal cell carcinoma of the prostrate (BCCP).
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Inhibiting metastatic breast cancer cell migration via the synergy of targeted, pH-triggered siRNA delivery and chemokine axis blockade.
Mol. Pharm.
PUBLISHED: 02-12-2014
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Because breast cancer patient survival inversely correlates with metastasis, we engineered vehicles to inhibit both the C-X-C chemokine receptor type 4 (CXCR4) and lipocalin-2 (Lcn2) mediated migratory pathways. pH-responsive liposomes were designed to protect and trigger the release of Lcn2 siRNA. Liposomes were modified with anti-CXCR4 antibodies to target metastatic breast cancer (MBC) cells and block migration along the CXCR4-CXCL12 axis. This synergistic approach--coupling the CXCR4 axis blockade with Lcn2 silencing--significantly reduced migration in triple-negative human breast cancer cells (88% for MDA-MB-436 and 92% for MDA-MB-231). The results suggested that drug delivery vehicles engineered to attack multiple migratory pathways may effectively slow progression of MBC.
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Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice.
Protein Cell
PUBLISHED: 01-29-2014
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Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.
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Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.
Int. J. Gynecol. Cancer
PUBLISHED: 01-28-2014
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The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract.
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The roles of spatial pattern and size variation in shaping height inequality of plant population.
Bull. Math. Biol.
PUBLISHED: 01-24-2014
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Game-theoretic models predict that there is an ESS height for the plant population to which all individual plants should converge. To attain this conclusion, the neighborhood factors were assumed to be equal for all the individual plants, and the spatial pattern and size variation of population were left without consideration, which is clearly not right for the scenario of plant competition. We constructed a spatially-explicit, individual-based model to explore the impacts of spatial structure and size variation on individual plant's height and population's height hierarchies under the light competition. The monomorphic equilibrium of height that all the individual plants will converge to only exists for a population growing in a strictly uniform spatial pattern with no size variation. When the spatial pattern of the population is non-uniform or there's size variation among individual plants, the critical heights that individual plants will finally reach are different from each other, and the height inequality at the end of population growth will increase when the population's spatial pattern's degree of deviation from uniform and population's size variation increase. Our results argue strongly for the importance of spatial pattern and neighborhood effects in generating the diversity of population's height growth pattern.
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Multiscale tumor spatiokinetic model for intraperitoneal therapy.
AAPS J
PUBLISHED: 01-22-2014
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This study established a multiscale computational model for intraperitoneal (IP) chemotherapy, to depict the time-dependent and spatial-dependent drug concentrations in peritoneal tumors as functions of drug properties (size, binding, diffusivity, permeability), transport mechanisms (diffusion, convection), spatial-dependent tumor heterogeneities (vessel density, cell density, pressure gradient), and physiological properties (peritoneal pressure, peritoneal fluid volume). Equations linked drug transport and clearance on three scales (tumor, IP cavity, whole organism). Paclitaxel was the test compound. The required model parameters (tumor diffusivity, tumor hydraulic conductivity, vessel permeability and surface area, microvascular hydrostatic pressure, drug association with cells) were obtained from literature reports, calculation, and/or experimental measurements. Drug concentration-time profiles in peritoneal fluid and plasma were the boundary conditions for tumor domain and blood vessels, respectively. The finite element method was used to numerically solve the nonlinear partial differential equations for fluid and solute transport. The resulting multiscale model accounted for intratumoral spatial heterogeneity, depicted diffusive and convective drug transport in tumor interstitium and across blood vessels, and provided drug flux and concentration as a function of time and spatial position in the tumor. Comparison of model-predicted tumor spatiokinetics with experimental results (autoradiographic data of 3H-paclitaxel in IP ovarian tumors in mice, 6 h posttreatment) showed good agreement (1% deviation for area under curve and 23% deviations for individual data points, which were several-fold lower compared to the experimental intertumor variations). The computational multiscale model provides a tool to quantify the effects of drug-, tumor-, and host-dependent variables on the concentrations and residence time of IP therapeutics in tumors.
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Biomimetic alginate/polyacrylamide porous scaffold supports human mesenchymal stem cell proliferation and chondrogenesis.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 01-05-2014
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We describe the development of alginate/polyacrylamide (ALG/PAAm) porous hydrogels based on interpenetrating polymer network structure for human mesenchymal stem cell proliferation and chondrogenesis. Three ALG/PAAm hydrogels at molar ratios of 10/90, 20/80, and 30/70 were prepared and characterized with enhanced elastic and rubbery mechanical properties, which are similar to native human cartilage tissues. Their elasticity and swelling properties were also studied under different physiological pH conditions. Finally, in vitro tests demonstrated that human mesenchymal stem cells could proliferate on the as-synthesized hydrogels with improved alkaline phosphatase activities. These results suggest that ALG/PAAm hydrogels may be a promising biomaterial for cartilage tissue engineering.
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Chartarlactams A-P, phenylspirodrimanes from the sponge-associated fungus Stachybotrys chartarum with antihyperlipidemic activities.
J. Nat. Prod.
PUBLISHED: 01-03-2014
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Chemical examination of the solid culture of the endophytic fungus Stachybotrys chartarum isolated from the sponge Niphates recondita resulted in the isolation of 16 new phenylspirodrimanes, named chartarlactams A-P (1-16), together with eight known analogues. Their structures were determined on the basis of extensive spectroscopic analysis, including X-ray single-crystal diffraction for the determination of the absolute configurations. The isoindolone-drimane dimer chartarlactam L (12) was determined as a new skeleton. Compounds 1-6 and 8-24 were evaluated for antihyperlipidemic effects in HepG2 cells, and the primary structure-activity relationships are discussed.
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miR-145 inhibits invasion of bladder cancer cells by targeting PAK1.
Urol. Oncol.
PUBLISHED: 01-02-2014
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MicroRNAs play important roles in cancer. In many cancers, miR-145 acts as a tumor suppressor, and it is down-regulated in bladder cancer. In the present study, we explored the modulation of oncogenic gene PAK1 by miR-145 in bladder cancer.
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Stereotactic aspiration versus craniotomy for primary intracerebral hemorrhage: a meta-analysis of randomized controlled trials.
PLoS ONE
PUBLISHED: 01-01-2014
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A wealth of evidence based on the randomized controlled trials (RCTs) has indicated that surgery may be a better choice in the management of primary intracerebral hemorrhage (ICH) compared to conservative treatment. However, there is considerable controversy over selecting appropriate surgical procedures for ICH. Thus, this meta-analysis was performed to assess the effects of stereotactic aspiration compared to craniotomy in patients with ICH.
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Gadd45a Regulates Hematopoietic Stem Cell Stress Responses in Mice.
Blood
PUBLISHED: 12-26-2013
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Gadd45a has been involved in DNA damage response and in many malignancies, including leukemia. However, the function of Gadd45a in hematopoietic stem cells (HSCs) remains unknown. Here, we reported that Gadd45a-deficient (Gadd45a(-/-)) mice showed a normal hematologic phenotype under homeostatic conditions. However, following 5-?uorouracil treatment, Gadd45a(-/-) HSCs exhibited a faster recovery, associated with an increase in the proliferation rate. Interestingly, young Gadd45a(-/-) HSCs showed enhanced reconstitution ability in serial transplantation. Following ionizing radiation (IR), young Gadd45a(-/-) HSCs exhibited an increased resistance to IR-induced DNA damage, associated with a decrease in the apoptosis rate and delayed DNA repair. The significantly higher level of DNA damage in Gadd45a(-/-) HSCs ultimately promoted B-cell leukemia in further transplanted recipient mice. In old mice, Gadd45a(-/-) HSCs were functionally equal to wild-type HSCs, but exhibited more DNA damage accumulation and increased sensitivity to IR than wild-type HSCs. In conclusion, Gadd45a plays a significant role in HSC stress responses. Gadd45a deficiency leads to DNA damage accumulation and impairment in apoptosis after exposure to IR, which increases the susceptibility of leukemogenesis.
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[Value of temporal bone dual phase contrast enhancement computed tomography in diagnosing causes of pulsatile tinnitus].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-24-2013
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To evaluate the value of temporal bone dual phase contrast enhancement computed tomography (DPCT) in diagnosing the causes of pulsatile tinnitus (PT).
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[Surveillance of bacterial distribution and drug resistance in inpatients with surgical infections: a single center study].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 11-22-2013
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To investigate the bacterial distribution and drug resistance in patients with surgical infections, and provide the basis for the standardization treatment of the surgical infection.
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Clinical and microbiological features of community-acquired and nosocomial bloodstream infections in the surgical department of a tertiary-care hospital in Beijing.
Chin. Med. J.
PUBLISHED: 11-19-2013
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Bloodstream infections (BSIs) remain a major cause of morbidity and mortality in patients undergoing surgery. This study aimed at elucidating the clinical characteristics of community-acquired BSIs (CABs) and nosocomial BSIs (nBSIs) in patients admitted to the surgical wards of a teaching hospital in Beijing, China.
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Modulation of Lipogenesis and Glucose Consumption in HepG2 Cells and C2C12 Myotubes by Sophoricoside.
Molecules
PUBLISHED: 11-04-2013
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Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1-10 ?M inhibited lipid accumulation in HepG2 cells in a dose-dependent manner. At the same concentration range, no effect on cell viability was observed in the MTT assay. Inhibition of lipogenesis was associated with the downregulation of SREBP-1a, SREBP-1c, SREBP-2 and their downstream target genes (FAS, ACC, HMGR) as revealed by realtime quantitative PCR. The lipid-lowering effect was mediated via the phosphorylation of AMPK. Further investigation of the activities of this isoflavone showed that sophoricoside has the capability to increase glucose uptake by C2C12 myotubes. It also effectively inhibited the activities of ?-glucosidase and ?-amylase in vitro and remarkably lowered postprandial hyperglycaemia in starch-loaded C57BL6/J mice. These results suggest that sophoricoside is an effective regulator of lipogenesis and glucose consumption and may find utility in the treatment of obesity and type 2 diabetes.
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The antidiabetic drug metformin inhibits the proliferation of bladder cancer cells in vitro and in vivo.
Int J Mol Sci
PUBLISHED: 10-28-2013
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Recent studies suggest that metformin, a widely used antidiabetic agent, may reduce cancer risk and improve prognosis of certain malignancies. However, the mechanisms for the anti-cancer effects of metformin remain uncertain. In this study, we investigated the effects of metformin on human bladder cancer cells and the underlying mechanisms. Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1. Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the central regulator of protein synthesis and cell growth. Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR. The in vitro and in vivo results demonstrate that metformin efficiently suppresses the proliferation of bladder cancer cells and suggest that metformin may be a potential therapeutic agent for the treatment of bladder cancer.
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[Surgical treatment of ruptured cerebellar arteriovenous malformations].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-16-2013
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To analyze the clinical characteristics and surgical outcomes of ruptured cerebellar arteriovenous malformations (AVM).
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Strong anti-ice ability of nanohairs over micro-ratchet structures.
Nanoscale
PUBLISHED: 10-14-2013
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A strong anti-ice property of nanohairs over micro-ratchet surfaces is observed. A long freezing delay of more than 185 min is achieved for a droplet on the nanohairs over ratchet structure with a period of ?290 ?m under -10 °C, which is attributed to the effective cooperation of the nano- and microstructures.
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Optical phase modulation based on directly modulated reflection-mode OIL-VCSEL.
Opt Express
PUBLISHED: 10-10-2013
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Optical phase modulation based on directly modulated reflection-mode optically injection-locked VCSEL is investigated based on standard OIL rate equations and reflection-mode OIL model. The phase information of both static and dynamic state is simulated. The difference of static state phase information between transmission- and reflection-mode OIL is numerically analyzed. With specific OIL parameters, the output power of directly modulated OIL-VCSEL remains constant and phase deviation of 0.934? rad is obtained. Results show that a directly modulated OIL-VCSEL can function as a key component in QPSK or 8PSK transmitters. Preliminary 2.5 Gb/s PSK modulation characteristic is demonstrated experimentally.
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Endoplasmic reticulum stress activates telomerase.
Aging Cell
PUBLISHED: 09-12-2013
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Telomerase contributes to cell proliferation and survival through both telomere-dependent and telomere-independent mechanisms. In this report, we discovered that endoplasmic reticulum (ER) stress transiently activates the catalytic components of telomerase (TERT) expression in human cancer cell lines and murine primary neural cells. Importantly, we show that depletion of hTERT sensitizes cells to undergo apoptosis under ER stress, whereas increased hTERT expression reduces ER stress-induced cell death independent of catalytically active enzyme or DNA damage signaling. Our findings establish a functional link between ER stress and telomerase, both of which have important implications in the pathologies associated with aging and cancer.
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[Impact of AMPKgamma silencing on AMPK activation and intracellular lipids regulation].
Yao Xue Xue Bao
PUBLISHED: 08-30-2013
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The study is aimed to confirm the silencing efficiency of the vector in human hepatocellular liver carcinoma cell line (HepG2), and observe effects of AMPKgamma silencing on the AMPK stimulating activity and lipid synthesis of cordycepin (CCS), a natural product with known AMPK activating function. The downregulating efficacy of siRNAs on AMPKgamma expression was confirmed in our previous study. The double stranded shRNA Oligo was ligated to lentivirus vector and verified by sequencing. The lentiviral which can effectively inhibited protein expression levels of AMPKgamma was selected by Western blotting, and the regulation of CCS on protein expression of AMPKgamma and p-AMPK in AMPKgamma silence cells were detected by Western blotting analysis. The lipid accumulation in cells was observed by Oil-Red O stain and cells were collected for the estimation of cholesterol (TC), triglyceride (TG). The results showed that the lentiviral vector carrying a shRNA targeting the AMPKgamma gene was successfully constructed. Western blotting analysis confirmed that GR085 had the highest interfering efficiency. Treatment with CCS can significantly increase the levels of phospho-AMPK in normal cells, and the level of TC, TG was reduced, but in AMPKgamma silence cells the effects of CCS on AMPK activation and lipid synthesis were almost completely abolished without changing the expression levels of total AMPK or AMPKgamma protein. In conclusion, the AMPKgamma gene may be related to AMPK activation and intracellular lipids regulation by CCS.
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[Animal experimental study of biodegradable magnesium alloy stapler for gastrointestinal anastomosis].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 08-28-2013
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To explore the safety and feasibility of biodegradable magnesium alloy stapler based on the result of animal experimental study for gastrointestinal anastomosis.
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Acyldepsipeptides inhibit the growth of renal cancer cells through G1 phase cell cycle arrest.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-27-2013
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Acyldepsipeptides are a group of potent antibiotics discovered in the secondary metabolites of Streptomyces species. However, besides the function of antibiotics, no other activities have been reported about these important compounds so far. In the course of searching the natural products as chemotherapeutic agents for renal cell carcinoma, we found that ADEP1, a major metabolic component of Streptomyces hawaiiensis NRRL 15010, could effectively inhibit the growth of 786-O, 769-P, and ACHN renal carcinoma cells in MTT assay. Flow cytometric analysis demonstrated that ADEP1 could block the cell cycle arrested at G1 phase. Moreover, it was found that ADEP1 down-regulated the expressions of cyclin D1, CDK4 and PCNA and inhibited activity of MAPK-ERK pathway by detection of decreased expression of phosphorylated ERK1/2 and c-Fos in 786-O and 769-P cells by Western blotting. To our knowledge, this is the first report concerning to the antitumor activities of acyldepsipeptides. Based on these results, ADEP1 may become a promising lead compound to be developed a novel chemotherapeutic agent for treatment of renal carcinoma.
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Exploring unsymmetrical dyads as efficient inhibitors against the insect ?-N-acetyl-d-hexosaminidase OfHex2.
Biochimie
PUBLISHED: 07-23-2013
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The GH20 ?-N-acetyl-d-hexosaminidase OfHex2 from the insect Ostrinia furnacalis (Guenée) is a target potential for eco-friendly pesticide development. Although carbohydrate-based inhibitors against ?-N-acetyl-d-hexosaminidases are widely studied, highly efficient, non-carbohydrate inhibitors are more attractive due to low cost and readily synthetic manner. Based on molecular modeling analysis of the catalytic domain of OfHex2, a series of novel naphthalimide-scaffold conjugated with a small aromatic moiety by an alkylamine spacer linker were designed and evaluated as efficiently competitive inhibitors against OfHex2. The most potent one containing naphthalimide and phenyl groups spanning by an N-alkylamine linker has a Ki value of 0.37 ?M, which is 6 fold lower than that of M-31850, the most potent non-carbohydrate inhibitor ever reported. The straightforward synthetic manners as well as the presumed binding model in this paper could be advantageous for further structural optimization for developing inhibitors against GH20 ?-N-acetyl-d-hexosaminidases.
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Interactions of newly designed dicationic carbazole derivatives with double-stranded DNA: syntheses, binding studies and AFM imaging.
Org. Biomol. Chem.
PUBLISHED: 07-19-2013
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The design of small molecular ligands able to bind with DNA is pivotal for the development of diagnostic agents and therapeutic drugs targeting DNA. Carbazole-derivatives are potential agents against tumors and opportunistic infections of AIDS. Here, two carbazole-derived dicationic compounds, DPDI and DPPDI, were designed, synthesized and characterized using NMR, IR and MS. The DNA binding properties of DPDI and DPPDI were sensitive to ionic strength. At low ionic strength, planar and aromatic DPDI had a strongly intercalative interaction with DNA, which was confirmed by circular dichroism (CD) and gel electrophoresis. In DPPDI, a phenyl group substituting H atom at the –NH group of DPDI destroyed molecular planarity, which resulted in no intercalative interactions between DPPDI and DNA, proved by CD. The positive enhancement of CD at 260–270 nm and Hoechst 33258 competitive binding tests indicated the strong groove interactions of both DPPDI and DPDI to DNA. The similarity and difference in the structures between DPDI and DPPDI explained different interaction preferences with DNA. In groove interactions, dications of pyridinium on either DPDI or DPPDI could interact with DNA base pairs, and –NH on DPDI or –N–Ph on DPPDI pointed out of the groove, as the classical model of DNA groove binding agents. Furthermore, AFM imaging revealed that both carbazole-derivatives drove the DNA conformation more compact. All the experimental data proved that the two dicationic carbazole-derivatives interacted with DNA strongly and might act as a novel type of DNA-binding candidate.
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Mitochondrial genome of Protobothrops maolanensis (Squamata: Viperidae: Crotalinae).
Mitochondrial DNA
PUBLISHED: 07-16-2013
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Abstract Protobothrops maolanensis was recently described from Guizhou, southwestern China. In this study, the complete mitochondrial genome of P. maolanensis had been determined. The circle genome with the 17,231?bp total length contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 control regions. Overall, base composition of the complete mtDNA was 32.96% A, 24.92% T, 29.41% C and 12.72% G. All the genes in P. maolanensis were distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes which were encoded on the L-strand.
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Silibinin inhibits ?-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness.
Cell. Signal.
PUBLISHED: 07-09-2013
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Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3? (GSK3?) phosphorylation, ?-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of ?-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness.
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Leaf cDNA-AFLP analysis of two citrus species differing in manganese tolerance in response to long-term manganese-toxicity.
BMC Genomics
PUBLISHED: 07-01-2013
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Very little is known about manganese (Mn)-toxicity-responsive genes in citrus plants. Seedlings of Xuegan (Citrus sinensis) and Sour pummelo (Citrus grandis) were irrigated for 17 weeks with nutrient solution containing 2 ?M (control) or 600 ?M (Mn-toxicity) MnSO?. The objectives of this study were to understand the mechanisms of citrus Mn-tolerance and to identify differentially expressed genes, which might be involved in Mn-tolerance.
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[The long lasting effect of the murine fibroblast growth factor-21 on blood glucose control of diabetic animals].
Yao Xue Xue Bao
PUBLISHED: 06-04-2013
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Insulin is the most common medicine used for diabetic patients, unfortunately, its effective time is short, even the long-acting insulin cannot obtain a satisfactory effect. Fibroblast growth factor (FGF)-21 is a recently discovered glucose mediator and expected to be a potential anti-diabetic drug that does not rely on insulin. In this study, db/db mice were used as the type 2 diabetic model to examine whether mFGF-21 has the long-term blood lowering effect on the animal model. The results showed that mFGF-21 could stably maintain the blood glucose at normal level for a long-term in a dose-dependent manner. Administration of mFGF-21 once a day with three doses (0.125, 0.25 and 0.5 mg x kg(-1)) could maintain blood glucose of the model animals at normal level for at least 24 h. Administration of mFGF-21 every two days with the same doses could maintain blood glucose of the model animals at normal level for at least 48 h, although it took longer time for blood glucose to reach to normal level depending on doses used (twenty injections for 0.125 mg x kg(-1) and 0.25 mg x kg(-1) doses, ten injections for 0.5 mg x kg(-1) dose). Surprisingly, the blood glucose of the treated model animals still maintained at normal level for 24 h after the experiment terminated. Glycosylated hemoglobin level of the animals treated with mFGF-21, which represented long-term glucose status, decreased significantly compared to the control group and the insulin group. The results suggest that FGF-21 has potential to become a long-acting and potent anti-diabetic drug.
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Cordycepin activates AMP-activated protein kinase (AMPK) via interaction with the ?1 subunit.
J. Cell. Mol. Med.
PUBLISHED: 06-03-2013
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Cordycepin is a bioactive component of the fungus Cordyceps militaris. Previously, we showed that cordycepin can alleviate hyperlipidemia through enhancing the phosphorylation of AMP-activated protein kinase (AMPK), but the mechanism of this stimulation is unknown. Here, we investigated the potential mechanisms of cordycepin-induced AMPK activation in HepG2 cells. Treatment with cordycepin largely reduced oleic acid (OA)-elicited intracellular lipid accumulation and increased AMPK activity in a dose-dependent manner. Cordycepin-induced AMPK activation was not accompanied by changes in either the intracellular levels of AMP or the AMP/ATP ratio, nor was it influenced by calmodulin-dependent protein kinase kinase (CaMKK) inhibition; however, this activation was significantly suppressed by liver kinase B1 (LKB1) knockdown. Molecular docking, fluorescent and circular dichroism measurements showed that cordycepin interacted with the ?1 subunit of AMPK. Knockdown of AMPK?1 by siRNA substantially abolished the effects of cordycepin on AMPK activation and lipid regulation. The modulating effects of cordycepin on the mRNA levels of key lipid regulatory genes were also largely reversed when AMPK?1 expression was inhibited. Together, these data suggest that cordycepin may inhibit intracellular lipid accumulation through activation of AMPK via interaction with the ?1 subunit.
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Assessing species boundaries and the phylogenetic position of the rare Szechwan ratsnake, Euprepiophis perlaceus (Serpentes: Colubridae), using coalescent-based methods.
Mol. Phylogenet. Evol.
PUBLISHED: 05-24-2013
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Delimiting species and clarifying phylogenetic relationships are the main goals of systematics. For species with questionable taxonomic status, species delimitation approaches using multi-species coalescent models with multiple loci are recommended if morphological data are unavailable or unhelpful. Moreover, these methods will also reduce subjectivity based on genetic distance or requirement of monophyletic genetic lineages. We determine the validity and phylogenetic position of a rare and long controversial species of Chinese reptile, the Szechwan ratsnake (Euprepiophis perlaceus), using multi-locus data from multiple individuals and coalescent-based approaches. Species were first delimited using Bayesian Phylogenetics & Phylogeography (BP&P), Brownie and Bayes Factor model comparison approaches, while relationships among species were estimated using species tree inference in (*)BEAST. Results indicate that Euprepiophis perlaceus is a distinct species sister to Euprepiophis mandarinus. Despite gene tree discrepancy, the coalescent model-based approaches used here demonstrate the taxonomic validity and the phylogenetic position of Euprepiophis perlaceus. These approaches objectively test the validity of questionable species diagnoses based on morphological characters and determine their phylogenetic position.
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What is Visualize?

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.