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Find video protocols related to scientific articles indexed in Pubmed.
Enhancement of Osteogenesis and Biodegradation Control by Brushite Coating on Mg-Nd-Zn-Zr Alloy for Mandibular Bone Repair.
ACS Appl Mater Interfaces
PUBLISHED: 10-25-2014
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To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Gieson's picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.
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Effects of mineral additives on biochar formation: carbon retention, stability, and properties.
Environ. Sci. Technol.
PUBLISHED: 09-24-2014
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Biochar is being recognized as a promising tool for long-term carbon sequestration, and biochar with high carbon retention and strong stability is supposed to be explored for that purpose. In this study, three minerals, including kaolin, calcite (CaCO3), and calcium dihydrogen phosphate [Ca(H2PO4)2], were added to rice straw feedstock at the ratio of 20% (w/w) for biochar formation through pyrolysis treatment, aiming to improve carbon retention and stabilization in biochar. Kaolin and CaCO3 had little effect on the carbon retention, whereas Ca(H2PO4)2 increased the carbon retention by up to 29% compared to untreated biochar. Although the carbon loss from the kaolin-modified biochar with hydrogen peroxide oxidation was enhanced, CaCO3 and Ca(H2PO4)2 modification reduced the carbon loss by 18.6 and 58.5%, respectively. Moreover, all three minerals reduced carbon loss of biochar with potassium dichromate oxidation from 0.3 to 38.8%. The microbial mineralization as CO2 emission in all three modified biochars was reduced by 22.2-88.7% under aerobic incubation and 5-61% under anaerobic incubation. Enhanced carbon retention and stability of biochar with mineral treatment might be caused by the enhanced formation of aromatic C, which was evidenced by cross-polarization magic angle spinning (13)C nuclear magnetic resonance spectra and Fourier transform infrared spectroscopy analysis. Our results indicated that the three minerals, especially Ca(H2PO4)2, were effective in increasing carbon retention and strengthening biochar stabilization, which provided a novel idea that people could explore and produce the designated biochar with high carbon sequestration capacity and stability.
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A Small-Molecule Modulator of the Tumor-Suppressor miR34a Inhibits the Growth of Hepatocellular Carcinoma.
Cancer Res.
PUBLISHED: 09-12-2014
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Small molecules that restore the expression of growth-inhibitory microRNAs (miRNA) downregulated in tumors may have potential as anticancer agents. miR34a functions as a tumor suppressor and is downregulated or silenced commonly in a variety of human cancers, including hepatocellular carcinoma (HCC). In this study, we used an HCC cell-based miR34a luciferase reporter system to screen for miR34a modulators that could exert anticancer activity. One compound identified as a lead candidate, termed Rubone, was identified through its ability to specifically upregulate miR34a in HCC cells. Rubone activated miR34a expression in HCC cells with wild-type or mutated p53 but not in cells with p53 deletions. Notably, Rubone lacked growth-inhibitory effects on nontumorigenic human hepatocytes. In a mouse xenograft model of HCC, Rubone dramatically inhibited tumor growth, exhibiting stronger anti-HCC activity than sorafenib both in vitro and in vivo. Mechanistic investigations showed that Rubone decreased expression of cyclin D1, Bcl-2, and other miR34a target genes and that it enhanced the occupancy of p53 on the miR34a promoter. Taken together, our results offer a preclinical proof of concept for Rubone as a lead candidate for further investigation as a new class of HCC therapeutic based on restoration of miR34a tumor-suppressor function. Cancer Res; 74(21); 6236-47. ©2014 AACR.
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Theoretical study of the formation of mercury (Hg2+) complexes in solution using an explicit solvation shell in implicit solvent calculations.
J Phys Chem B
PUBLISHED: 09-12-2014
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The structures and harmonic vibrational frequencies of water clusters (H2O)n, n = 1-10, have been computed using the M06-L/, B3LYP/, and CAM-BLYP/cc-pVTZ levels of theories. On the basis of the literature and our results, we use three hexamer structures of the water molecules to calculate an estimated "experimental" average solvation free energy of [Hg(H2O)6](2+). Aqueous formation constants (log K) for Hg(2+) complexes, [Hg(L)m(H2O)n](2-mq), L = Cl(-), HO(-), HS(-), and S(2-), are calculated using a combination of experimental (solvation free energies of ligands and Hg(2+)) and calculated gas- and liquid-phase free energies. A combined approach has been used that involves attaching n explicit water molecules to the Hg(2+) complexes such that the first coordination sphere is complete, then surrounding the resulting (Hg(2+)-Lm)-(OH2)n cluster by a dielectric continuum, and using suitable thermodynamic cycles. This procedure significantly improves the agreement between the calculated log K values and experiment. Thus, for some neutral and anionic Hg(II) complexes, particularly Hg(II) metal ion surrounded with homo- or heteroatoms, augmenting implicit solvent calculations with sufficient explicit water molecules to complete the first coordination sphere is required-and adequate-to account for strong short-range hydrogen bonding interactions between the anion and the solvent. Calculated values for formation constants of Hg(2+) complexes with S(2-) and SH(-) are proposed. Experimental measurements of these log K values have been lacking or controversial.
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[Symbiotic efficiency and genetic diversity of the rhizobia isolated from Leucaena leucocephala in Liangshan Prefecture].
Wei Sheng Wu Xue Bao
PUBLISHED: 09-10-2014
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We analyzed the symbiotic efficiency and genetic diversity of rhizobia isolated from Leucaena leucocephala in Liangshan Prefecture of SichuanProvince.
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Ferroelectric switching of elastin.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-23-2014
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Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 ?C/cm(2), whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications.
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Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve.
Mol Med Rep
PUBLISHED: 05-19-2014
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There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. Caspases are the key regulators of apoptosis. Healthy male Sprague?Dawley rats were used in the present study to examine the radioprotective effect of a type of pan-caspase inhibitor, z-VAD-fmk, following radiation, to investigate the effects of caspase blockade in a model of the nucleus of the abducens nerve. z-VAD-fmk was injected intracerebroventricularly as a bolus injection (0.2 µg/h for 1 h) into rats prior to exposure to radiation. Irradiation was conducted at room temperature at a dose of radiation of 4 Gy. The present study performed immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot analysis and identified no significant changes in the expression of the X-linked inhibitor of apoptosis protein (XIAP) following radiation (P>0.05). As compared with the radiation alone group, the quantification of TUNEL-positive neurons was reduced in z-VAD?fmk-treated animals following radiation (P<0.01). Inhibition of caspase induced by z-VAD?fmk reduced the expression and activation of caspase-3, -8 and -9 (P<0.01). z-VAD-fmk effectively prevented radiation-induced apoptosis and this caspase inhibitor may be a potential therapeutic target in the treatment of brain radiation injury. The nucleus of the abducens nerve may be used as a radiation injury model, providing visual information and data on the apoptotic morphology of the abducens nucleus.
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A validated RP-HPLC method to investigate finasteride in human skin after in vitro topically applying vesicular nanocarrier.
Pak J Pharm Sci
PUBLISHED: 05-10-2014
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The pharmacotherapeutic efficiency of topical drug delivery systems is mainly dominated by the skin distribution of therapeutic agents. In this work, a sensitive, rapid and fully-validated reversed-phase high performance liquid chromatography (RP-HPLC) method was developed to determine finasteride in human cadaver skin after different vesicular formulations were applied. Drug in different depth of skin layers were measured with an EclipseXDB-C18 column. The mobile phase consisted of 75% (v/v) methanol containing 0.2% phosphoric acid buffered to pH 3.0 with triethylamine under isocratic conditions. The system was operated at 40°C and the mobile phase flow rate was set at 1 mL/min. The standard-calibration curve was linear within range of 5 to 200 ng/ml with correlation coefficient 0.9996. The intra-assay precision was less than 3.9% while the inter-assay precision was less than 7.1% with the bias range of -8.6 to 4.1%. This method was found to be specific, accurate, and sensitive and was successfully used to determine the accumulation of finasteride after in-vitro percutaneous delivery by liposomal or ethosomal drug delivery nanocarriers.
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Total and methylated mercury in Arctic multiyear sea ice.
Environ. Sci. Technol.
PUBLISHED: 05-08-2014
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Mercury is one of the primary contaminants of concern in the Arctic marine ecosystem. While considerable efforts have been directed toward understanding mercury cycling in the Arctic, little is known about mercury dynamics within Arctic multiyear sea ice, which is being rapidly replaced with first-year ice. Here we report the first study on the distribution and potential methylation of mercury in Arctic multiyear sea ice. Based on three multiyear ice cores taken from the eastern Beaufort Sea and McClure Strait, total mercury concentrations ranged from 0.65 to 60.8 pM in bulk ice, with the highest values occurring in the topmost layer (?40 cm) which is attributed to the dynamics of particulate matter. Methylated mercury concentrations ranged from below the method detection limit (<0.1 pM) to as high as 2.64 pM. The ratio of methylated to total mercury peaked, up to ?40%, in the mid to bottom sections of the ice, suggesting the potential occurrence of in situ mercury methylation. The annual fluxes of total and methylated mercury into the Arctic Ocean via melt of multiyear ice are estimated to be 420 and 42 kg yr(-1), respectively, representing an important and changing source of mercury and methylmercury into the Arctic Ocean marine ecosystem.
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Coffee consumption and risk of gastric cancer: a large updated meta-analysis of prospective studies.
Nutrients
PUBLISHED: 05-07-2014
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The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed and Embase databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93-1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06-1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00-1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13-1.93). There was some evidence of publication bias (P for Egger's test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation.
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Lycium barbarum polysaccharide attenuates alcoholic cellular injury through TXNIP-NLRP3 inflammasome pathway.
Int. J. Biol. Macromol.
PUBLISHED: 04-22-2014
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Lycium barbarum has been used as a traditional Chinese medicine to nourish liver, kidneys and the eyes. However, the underlying mechanisms of its hepatic-protective properties remain uncertain. In this study, we aimed to investigate whether thioredoxin-interacting protein (TXNIP) and NOD-like receptor 3 (NLRP3) inflammasome mediated the attenuation of ethanol-induced hepatic injury by Lycium barbarum polysaccharide (LBP). Rat normal hepatocyte line BRL-3A was pre-treated with LBP prior to ethanol incubation. Hepatic damages, including apoptosis, inflammation, and oxidative stress, were measured. Then the inhibition of endogenous TXNIP expression was achieved by using its specific siRNA to test its possible involvement in the injury attenuation. We found that 50?g/ml LBP pre-treatment significantly alleviated 24-h ethanol exposure-induced overexpression of TXNIP, increased cellular apoptosis, secretion of inflammatory cytokines, activation of NLRP3 inflammasome, production of ROS, and reduced antioxidant enzyme expression. Silence of TXNIP suppressed the activated NLRP3 inflammasome, increased oxidative stress and worsened apoptosis in the cells. Further addition of LBP did not influence the effects of TXNIP inhibition on the cells. In conclusion, inhibition of hepatic TXNIP by LBP contributes to the reduction of cellular apoptosis, oxidative stress and NLRP3 inflammasome-mediated inflammation.
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Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery.
Drug Dev Ind Pharm
PUBLISHED: 04-22-2014
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Abstract Context: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on. Objective: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers. Methods: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates. Results and discussion: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ?12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX. Conclusion: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.
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Bioinspired materials: from low to high dimensional structure.
Adv. Mater. Weinheim
PUBLISHED: 04-15-2014
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The surprising properties of biomaterials are the results of billions of years of evolution. Generally, biomaterials are assembled under mild conditions with very limited supply of constituents available for living organism, and their amazing properties largely result from the sophisticated hierarchical structures. Following the biomimetic principles to prepare manmade materials has drawn great research interests in materials science and engineering. In this review, we summarize the recent progress in fabricating bioinspired materials with the emphasis on mimicking the structure from one to three dimensions. Selected examples are described with a focus on the relationship between the structural characters and the corresponding functions. For one-dimensional materials, spider fibers, polar bear hair, multichannel plant roots and so on have been involved. Natural structure color and color shifting surfaces, and the antifouling, antireflective coatings of biomaterials are chosen as the typical examples of the two-dimensional biomimicking. The outstanding protection performance, and the stimuli responsive and self-healing functions of biomaterials based on the sophisticated hierarchical bulk structures are the emphases of the three-dimensional mimicking. Finally, a summary and outlook are given.
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AP-2? downregulation by cigarette smoke condensate is counteracted by p53 in human lung cancer cells.
Int. J. Mol. Med.
PUBLISHED: 03-29-2014
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Cumulative findings have demonstrated that the dysregulation of tumor suppressor genes may be implicated in cigarette smoke-induced carcinogenesis. Activating enhancer-binding protein 2 (AP-2) is a eukaryotic transcriptional factor that plays a significant role in embryonic development and tumorigenesis. The vertebrate AP-2 family consists of AP-2?, AP-2?, AP-2?, AP-2? and AP-2?. Previous studies have suggested that cigarette smoking disrupts AP-2 regulation. In the present study, we investigated the effects of cigarette smoke condensate (CSC) on AP-2? expression in human lung cancer cell lines (NCI-H1299, NCI-H446 and A549), as well as the potential mechanisms involved. Using RT-qPCR, we found that CSC decreased AP-2? expression by suppressing its transcription in human lung cancer cell lines, particularly in p53-deficient NCI-H1299 cells. Western blotting and luciferase assays were implemented and we found that the restoration of p53 expression rescued the NCI-H1299 cells from CSC-induced AP-2? loss, while the silencing of p53 resulted in increased AP-2? loss induced by CSC, suggesting an antagonizing role of p53 in the regulation of AP-2? by CSC. Our results indicate that AP-2? downregulation may be involved in smoke-induced lung carcinogenesis.
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Combating non-Hodgkin lymphoma by targeting both CD20 and HLA-DR through CD20-243 CrossMab.
MAbs
PUBLISHED: 03-26-2014
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Although rituximab has revolutionized the treatment of hematological malignancies, the acquired resistance is one of the prime obstacles for cancer treatment, and development of novel CD20-targeting antibodies with potent anti-tumor activities and specificities is urgently needed. Emerging evidence has indicated that lysosomes can be considered as an "Achilles heel" for cancer cells, and might serve as an effective way to kill resistant cancer cells. HLA-DR antibody L243 has been recently reported to elicit potent lysosome-mediated cell death in lymphoma and leukemia cells, suggesting that HLA-DR could be used as a potential target against lymphoma. In this study, we generated a bispecific immunoglobulin G-like antibody targeting both CD20 and HLA-DR (CD20-243 CrossMab) through CrossMab technology. We found that the CrossMab could induce remarkably high levels of complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and anti-proliferative activity. Notably, although HLA-DR is expressed on normal and malignant cells, the CrossMab exhibited highly anti-tumor specificity, showing efficient eradication of hematological malignancies both in vitro and in vivo. Our data indicated that combined targeting of CD20 and HLA-DR could be an effective approach against malignancies, suggesting that CD20-243 CrossMab would be a promising therapeutic agent against lymphoma.
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[Inhibitory effect of resveratrol on expression of IL-1? in mesenchymal stem cells exposed to radiation].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 03-18-2014
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To investigate the inhibitory effect of resveratrol on interleukin-1? (IL-1?) production in mesenchymal stem cells (MSCs) exposed to radiation and the action mechanism of resveratrol.
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Hepatitis B virus X protein promotes hepatocellular carcinoma transformation through interleukin-6 activation of microRNA-21 expression.
Eur. J. Cancer
PUBLISHED: 03-06-2014
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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and chronic hepatitis B virus (HBV) infection is the major risk factor of HCC. The virus encodes HBV X (HBx) protein that plays a critical role in the development of HCC. Studies have revealed numerous HBx-altered genes and signalling pathways that heavily contribute to tumourigenesis of non-tumour hepatocytes. However, the role of HBx in regulating other critical gene regulators such as microRNAs is poorly understood, which impedes the exploration of a complete HBx-associated carcinogenic network. Besides, critical microRNAs that drive the transformation of non-tumour hepatocytes are yet to be identified. Here, we overexpressed C-terminal truncated HBx protein in a non-tumour hepatocyte cell line MIHA, and measured a panel of cancer-associated miRNAs. We observed that oncogenic miR-21 was upregulated upon ectopic expression of this viral protein variant. HBx-miR-21 pathway was prevalent in HCC cells as inhibition of HBx in Hep3B and PLC/PRF/5 cells significantly suppressed miR-21 expression. Subsequently, we showed that the upregulation of miR-21 was mediated by HBx-induced interleukin-6 pathway followed by activation of STAT3 transcriptional factor. The high dependency of miR-21 expression to HBx protein suggested a unique viral oncogenic pathway that could aberrantly affect a network of gene expression. Importantly, miR-21 was essential in the HBx-induced transformation of non-tumour hepatocytes. Inhibition of miR-21 effectively attenuated anchorage-independent colony formation and subcutaneous tumour growth of MIHA cells. Our study suggested that overexpression of miR-21 was critical to promote early carcinogenesis of hepatocytes upon HBV infection.
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Ultrasmall Au(10-12)(SG)(10-12) nanomolecules for high tumor specificity and cancer radiotherapy.
Adv. Mater. Weinheim
PUBLISHED: 02-24-2014
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Radiosensitizers can increase local treatment efficacy under a relatively low and safe radiation dose, thereby facilitating tumor eradication and minimizing side effects. Here, a new class of radiosensitizers is reported, which contain several gold (Au) atoms embedded inside a peptide shell (e.g., Au10-12 (SG)10-12 ) and can achieve ultrahigh tumor uptake (10.86 SUV at 24 h post injection) and targeting specificity, efficient renal clearance, and high radiotherapy enhancement.
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Comparative study of minimally invasive versus open esophagectomy for esophageal cancer in a single cancer center.
Chin. Med. J.
PUBLISHED: 02-19-2014
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In order to minimize the injury reaction during the surgery and reduce the morbidity rate, hence reducing the mortality rate of esophagectomy, minimally invasive esophagectomy (MIE) was introduced. The aim of this study was to compare the postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing minimally invasive or open esophagectomy (OE).
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Sp1 modification of human endothelial nitric oxide synthase promoter increases the hypoxia-stimulated activity.
Microvasc. Res.
PUBLISHED: 02-05-2014
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Human endothelial nitric oxide synthase (eNOS) gene has a TATA-less weak promoter with a low activity. The aim of this study was to increase eNOS promoter activity by modification. Human eNOS promoter was modified by inserting a Sp1 element at a -74 bp site and function of the modified promoter was investigated via a hypoxia model induced by cobalt chloride in human umbilical vein endothelial cells. The results demonstrated that the Sp1-modified promoter resulted in a significant increase of normalized luciferase activity in the presence of hypoxia. There was a correlation between the transcriptional activity of the Sp1-modified promoter and the level of eNOS expression with enhancement of nitric oxide production. Together, these data indicate that human eNOS promoter activity is increased by inserting Sp1 binding site into the GC-rich region of the promoter in response to hypoxia, suggesting that this provides an approach to ameliorate microcirculation barrier of some cardiovascular disease and to study its mechanistic process.
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[Epidemiological characteristics of burn workers in Hunan Province].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 01-30-2014
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To understand the epidemiological characteristics of workers who are burn patients, and to provide basis for prevention and treatment of burn at work.
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Lycium barbarum polysaccharides therapeutically improve hepatic functions in non-alcoholic steatohepatitis rats and cellular steatosis model.
Sci Rep
PUBLISHED: 01-29-2014
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This study aimed to investigate the possible therapeutic effects and active components of Lycium barbarum polysaccharides (LBP) on a high fat diet-induced NASH rat model. We induced NASH in a rat model by voluntary oral feeding with a high-fat diet ad libitum for 8 weeks. After 8 weeks, 1?mg/kg LBP was orally administered for another 4 weeks with a high-fat diet. When compared with NASH rats treated for 12 weeks, therapeutic LBP treatment for 4 weeks during 12 weeks of NASH induction showed ameliorative effects on: (1) increased body and wet liver weights; (2) insulin resistance and glucose metabolic dysfunction; (3) elevated level of serum aminotransferases; (4) fat accumulation in the liver and increased serum free fatty acid (FFA) level; (5) hepatic fibrosis; (6) hepatic oxidative stress; (7) hepatic inflammatory response; and (8) hepatic apoptosis. These improvements were partially through the modulation of transcription factor NF-?B, MAPK pathways and the autophagic process. In a palmitate acid-induced rat hepatocyte steatosis cell-based model, we also demonstrated that l-arabinose and ?-carotene partially accounted for the beneficial effects of LBP on the hepatocytes. In conclusion, LBP possesses a variety of hepato-protective properties which make it a potent supplementary therapeutic agent against NASH in future clinical trials.
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Radioprotective and antioxidant effect of resveratrol in hippocampus by activating Sirt1.
Int J Mol Sci
PUBLISHED: 01-25-2014
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Reactive oxygen species can lead to functional alterations in lipids, proteins, and nucleic acids, and an accumulation of ROS (Reactive oxygen species) is considered to be one factor that contributes to neurodegenerative changes. An increase in ROS production occurs following irradiation. Neuronal tissue is susceptible to oxidative stress because of its high oxygen consumption and modest antioxidant defenses. As a polyphenolic compound, resveratrol is frequently used as an activator of Sirt1 (Sirtuin 1). The present study was designed to explore the radioprotective and antioxidant effect of resveratrol on Sirt1 expression and activity induced by radiation and to provide a new target for the development of radiation protection drugs. Our results demonstrate that resveratrol inhibits apoptosis induced by radiation via the activation of Sirt1. We demonstrated an increase in Sirt1 mRNA that was present on 21 days of resveratrol treatment following irradiation in a concentration-dependent manner. Such mRNA increase was accompanied by an increase of Sirt1 protein and activity. Resveratrol effectively antagonized oxidation induced by irradiation, supporting its cellular ROS-scavenging effect. These results provide evidence that the mitochondrial protection and the antioxidant effect of resveratrol contribute to metabolic activity. These data suggest that Sirt1 may play an important role to protect neurons from oxidative stress.
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Nested PCR for mtDNA-4977-bp deletion and comet assay for DNA damage - a combined method for radiosensitivity evaluation of tumor cells.
Oncol Lett
PUBLISHED: 01-22-2014
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To identify an effective method of evaluating the radiosensitivity of human tumor cell lines in vitro, the present study adopted mtDNA-4977-bp deletion coupled with comet assay. The three human tumor cell lines applied were HepG2, EC-9706 and MCF-7. The surviving fraction (SF), ratio of the mtDNA-4977-bp deletion and DNA damage were detected by MTT assay, nested polymerase chain reaction (PCR) technique and comet assay, respectively. Clearly, lower SFs were found for the HepG2 and EC-9706 cells as compared with the MCF-7 cells following irradiation at doses of 2, 4 and 8 Gy, indicating a higher radiosensitivity for the HepG2 and EC-9706 cells. Additionally, no significant differences were identified in the mtDNA-4977-bp deletions found among HepG2, EC-9706 and MCF-7 cells by PCR following 1- or 4-Gy ?-ray irradiation, while increased deletion ratios of mtDNA-4977 bp were observed in HepG2 and EC-9706 cells following 8-Gy irradiation, in contrast to decreases in MCF-7 cells. The most notable differences among these three tumor cell lines were observed by comet assay following 8-Gy ?-ray irradiation. A combined method of nested PCR and comet assay, therefore, is the most effective and accurate method in evaluating the radiosensitivity of tumor cells.
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shRNA-mediated XRCC2 gene knockdown efficiently sensitizes colon tumor cells to X-ray irradiation in vitro and in vivo.
Int J Mol Sci
PUBLISHED: 01-16-2014
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Colon cancer is one of the most common tumors of the digestive tract. Resistance to ionizing radiation (IR) decreased therapeutic efficiency in these patients' radiotherapy. XRCC2 is the key protein of DNA homologous recombination repair, and its high expression is associated with enhanced resistance to DNA damage induced by IR. Here, we investigated the effect of XRCC2 silencing on colon tumor cells' growth and sensitivity to X-radiation in vitro and in vivo. Colon tumor cells (T84 cell line) were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. The suppression of XRCC2 expression was achieved by using vector-based short hairpin RNA (shRNA) in T84 cells. We found that the knockdown of XRCC2 expression effectively decreased T84 cellular proliferation and colony formation, and led to cell apoptosis and cell cycle arrested in G2/M phase induced by X-radiation in vitro. In addition, tumor xenograft studies suggested that XRCC2 silencing inhibited tumorigenicity after radiation treatment in vivo. Our data suggest that the suppression of XRCC2 expression rendered colon tumor cells more sensitive to radiation therapy in vitro and in vivo, implying XRCC2 as a promising therapeutic target for the treatment of radioresistant human colon cancer.
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Radiation-induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z-VAD-fmk in the hypoglossal nucleus.
Exp Ther Med
PUBLISHED: 01-08-2014
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Numerous studies have demonstrated that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. To investigate the role of caspase, a cell permeable pan-caspase inhibitor, z-VAD-fmk [N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone], was used to investigate the effects of caspase blockade in vivo following irradiation. Adult male Sprague-Dawley rats (weight, 250-300 g) underwent irradiation at room temperature with a 4-Gy dose of radiation. Since z-VAD-fmk does not penetrate the blood-brain barrier, it was applied intracerebroventricularly via a bolus injection (0.2 ?g/h for 1 h). Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) demonstrated that z-VAD-fmk reduced the numbers of TUNEL-positive cells within the hypoglossal nucleus, suggesting that intervention in the caspase cascade following radiation may have therapeutic applications. The caspase inhibitor z-VAD-fmk reduced the expression and activation of caspase-3, caspase-8 and caspase-9 in the irradiated rats, indicating that caspase may be a potential therapeutic target in the treatment of brain radiation injury. Treatment with z-VAD-fmk also reduced the appearance of cytochrome c within the cytosolic fraction following radiation. The hypoglossal nucleus may be used as a model of radiation-induced injury in the central nervous system, providing visual information and displaying apoptotic nuclear morphology.
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Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic fatty liver disease model through modulating MAPK pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-?B) through the restoration of its inhibitor kappa B alpha (I?B?), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases.
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A random, case-control study on the efficacy and safety of Weishi Bitong Xifang fumigation for mild and moderate knee osteoarthritis patients.
Int J Rheum Dis
PUBLISHED: 11-21-2013
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To explore the efficacy and safety of Weishi Bitong Xifang fumigation for treating patients with knee osteoarthritis (KOA).
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Linear segmentation algorithm for detecting layer boundary with lidar.
Opt Express
PUBLISHED: 11-13-2013
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The automatic detection of aerosol- and cloud-layer boundary (base and top) is important in atmospheric lidar data processing, because the boundary information is not only useful for environment and climate studies, but can also be used as input for further data processing. Previous methods have demonstrated limitations in defining the base and top, window-size setting, and have neglected the in-layer attenuation. To overcome these limitations, we present a new layer detection scheme for up-looking lidars based on linear segmentation with a reasonable threshold setting, boundary selecting, and false positive removing strategies. Preliminary results from both real and simulated data show that this algorithm cannot only detect the layer-base as accurate as the simple multi-scale method, but can also detect the layer-top more accurately than that of the simple multi-scale method. Our algorithm can be directly applied to uncalibrated data without requiring any additional measurements or window size selections.
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Bibliometric analysis of Nobelists awards and landmark papers in physiology or medicine during 1983-2012.
Ann. Med.
PUBLISHED: 11-07-2013
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This studys purpose was to determine if there was a relationship between Nobel Laureates awards and landmark papers and winning the Nobel Prize in Physiology or Medicine during 1983-2012.
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Removal and transformation of effluent organic matter (EfOM) in biotreated textile wastewater by GAC/O3 pre-oxidation and enhanced coagulation.
Environ Technol
PUBLISHED: 11-07-2013
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GAC/O3 (ozonation in the presence of granular activated carbon) combined with enhanced coagulation was employed to process biotreated textile wastewater for possible reuse. The doses of ozone, GAC and coagulant were the variables studied for optimization. The effects of different treatment processes on effluent organic matter (EfOM) characteristics, including biodegradability, hydrophobic and hydrophilic nature, and apparent molecular weight (AMW) distribution were also investigated. Compared with ozonation, GAC/O3 not only presented a higher pre-oxidation efficiency, but also improved the treatability of hydrophobic and high molecular weight compounds by enhanced coagulation. After treatment by GAC/O3 pre-oxidation (0.6 mg O3 x mg(-1) COD and 20 g x L(-1) GAC) and enhanced coagulation (25 mg x L(-1) Al3+ at pH 5.5), the removal efficiencies of chemical oxygen demand (COD), dissolved organic carbon (DOC) and colour were higher than those for coagulation alone by 17.3%, 12.0% and 25.6%, respectively. Residual organic matter consisted mainly of hydrophobic acids and hydrophilic compounds of AMW < 1 kDa, which were colourless and of limited biological availability. The combination of GAC/O3 and enhanced coagulation was proved to be a simple and effective treatment strategy for removing EfOM from biotreated textile wastewater.
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Complete Genome Sequence of an H12N8 Avian Influenza Virus Isolated from Wild Bird Feces in Hunan East Dongting Lake National Nature Reserve.
Genome Announc
PUBLISHED: 10-26-2013
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An H12N8 subtype avian influenza virus (AIV) was isolated from a wild bird in China in 2011. It is the first report of isolation of the H12N8 subtype AIV in Asia. Phylogenetic analysis results suggested it is a reassortant, and all eight gene segments belong to the Eurasian gene pool.
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Penetration profile and human cadaver skin distribution of finasteride from vesicular nanocarriers.
Drug Deliv
PUBLISHED: 10-08-2013
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Abstract The skin accumulation of therapeutic agents affects the efficiency of topical drug delivery. In this study, in vitro distribution of finasteride of ethosomes and liposomes in human cadaver skin after percutaneous delivery were investigated. Experiments were performed using modified Franz diffusion cells. Finasteride ethosomes, liposomes or hydroethanolic solutions were used as donor medium. Drug distribution at different skin layers and depths were studied by hotplate separation and frozen horizontal slicing technique. The result showed that the accumulation of finasteride in skin ranged from 9.7-24.3??g/cm(2) at 12 or 24 hours. The ethosomes demonstrated better enhancing ability to deliver finasteride into the dermis layer than liposomes did. The finasteride concentration in the dermis layer from ethosomes was more than sevenfold higher than from liposomes. The finasteride accumulation in ethosomes group showed a distinctive reversed distribution profile. This distinctive reversed distribution profile is meaningful for exerting a favorable pharmacological effect for finasteride. The drug distribution profile in skin layers showed no significant difference between 12 and 24 hours application (p?>?0.05). The study demonstrated that finasteride can be accumulated at target site more effectively and maintained at higher level through the application of novel ethosomal carriers.
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[The construction and the expression of V5 epitope fused human androgen receptor vector in the yeast cell].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 09-25-2013
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When we try to establish the gene recombinant yeast cell to screen the androgenic endocrine disruptors, the key procedure is the androgen receptor (AR) expression in the yeast cell. For this purpose, we obtained the GPD (glyceraldehyde-3-phosphote dehydrogenase) promoter from the yeast genosome of W303-1A using PCR system and inserting it into Swa I and BamH I sites of pYestrp2. The new constructed vector was named pGPD. The V5 epitope tag DNA with a 5-BamH I and a 3-EcoR I sticky end was cloned into the corresponding site of the pGPD vector to yield the vector of pGPDV5. The 2 723 bp full length AR ORF amplified by PCR from pcDNA3.1/AR was fused to V5 epitope tag DNA in pGPDV5 to give the AR yeast expression vector of pGPDV5/AR. This fused vector was transformed into the yeast cell (W303-1A). Western blot was used to detect the V5 fused protein of AR, in the protocol of which the primary monoclonal antibody (IgG(2a)) of mouse anti-V5 and the polyclonal secondary antibody of goat anti-mouse (IgG) linked to horseradish peroxidase (HRP) were used to detect the specific protein in the given sample of the transformed yeast extract. The result showed that the fused protein of AR was expressed successfully in the yeast cell.
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p38? subtype is a potential target to inhibit eNOS activity and NO production in human endothelial cells.
Microvasc. Res.
PUBLISHED: 08-30-2013
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Human endothelial nitric oxide synthase (eNOS) activity is important for maintaining blood pressure homeostasis and vascular integrity through nitric oxide (NO).The in vitro study aimed at investigating a role of p38? signaling in modulating NO production in human umbilical vein endothelial cell-12 (HUVEC-12). Consistent with the stimulation of lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-?, the over-expression of p38? markedly down-regulated the eNOS promoter activity in HUVEC-12, which could be reversed by its negative mutant p38? (AF) or p38-specific inhibitor SB203580. Compared to the stimulation of LPS or TNF-?, p38?-targeting siRNA decreased the expressions of phosphorylated and non-phosphorylated p38?, and increased the promoter activity, an eNOS mRNA level and a phosphorylated eNOS protein expression with the enhancement of NO, which could be abrogated by the scrambled siRNA. The in situ eNOS protein expression in the cells treated by p38?-targeting siRNA was also higher than that of the control, following the corresponding attenuation of a p38 level, and mainly localized in the inner membrane and cytoplasm. These results indicate that the p38? subtype may be a potential target to down-regulate the eNOS activity and NO production in human endothelial cells.
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Anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins.
Pharmacol Rep
PUBLISHED: 06-08-2013
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Recent studies have shown that anisomycin significantly inhibits mammalian cell proliferation, but its mechanism remains unclear. In this study, Jurkat T cells were used to first explore a relationship between effect of anisomycin on them and alteration of cell cycle-regulating proteins.
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High sensitivity piezomagnetic force microscopy for quantitative probing of magnetic materials at the nanoscale.
Nanoscale
PUBLISHED: 05-29-2013
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Accurate scanning probing of magnetic materials at the nanoscale is essential for developing and characterizing magnetic nanostructures, yet quantitative analysis is difficult using the state of the art magnetic force microscopy, and has limited spatial resolution and sensitivity. In this communication, we develop a novel piezomagnetic force microscopy (PmFM) technique, with the imaging principle based on the detection of magnetostrictive response excited by an external magnetic field. In combination with the dual AC resonance tracking (DART) technique, the contact stiffness and energy dissipation of the samples can be simultaneously mapped along with the PmFM phase and amplitude, enabling quantitative probing of magnetic materials and structures at the nanoscale with high sensitivity and spatial resolution. PmFM has been applied to probe magnetic soft discs and cobalt ferrite thin films, demonstrating it as a powerful tool for a wide range of magnetic materials.
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Enhanced Tumor Accumulation of Sub-2 nm Gold Nanoclusters for Cancer Radiation Therapy.
Adv Healthc Mater
PUBLISHED: 05-15-2013
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A new type of metabolizable and efficient radiosensitizers for cancer radiotherapy is presented by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nanoconstruct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.
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[Establishment of recombinant Lac Z reporter gene-transformed yeast cells for bioassay of androgen-like compounds in environment].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 05-07-2013
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To establish the yeast-based bioassay system for the androgenic endocrine disruptors in the environment.
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Ionomycin inhibits Jurkat T cell behaviors in the presence of phorbol-12,13-dibutyrate.
Ann. Hematol.
PUBLISHED: 05-03-2013
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Ionomycin in conjunction with phorbol-12,13-dibutyrate (PDBu) is conventionally used as a stimulator to activate cells, especially original T cells. But we accidently found it had an entirely opposite action on malignant tumor cells derived from T cells. Thus, influence of ionomycin on human leukemia Jurkat T cell behaviors and its preliminary mechanistic process were explored in the presence of PDBu. Ionomycin could remarkably inhibit colony formation of the cells, and inhibitory rate of the cell proliferation was increased with ionomycin treatment in a dose- or time-related relationship, following the reduction of ERK1/2 and phosphorylated-ERK1/2 levels. However, a high dose of ionomycin might moderately repress mid-stage activation of the cells. It also blocked the cell entry at S-phase and G2/M-phase with the attenuation of transforming growth factor-? (TGF-?) level in the cells, and promoted the cell apoptosis following the augment of caspase-3 and cleaved caspase-3 in the cells. The dramatic elevation of [Ca2(+)]i and intracellular pH (pHi) was simultaneously followed by the above alteration of the cell behaviors. These results indicate that ionomycin may strongly inhibit human acute T lymphocyte leukemia progress in the presence of PDBu through the inhibition of ERK1/2 signaling, the activation of caspase-3 and the attenuation of TGF-? mediated by the [Ca2(+)]i and pHi enhancement, providing a novel insight into function and potential application of both ionomycin and PDBu.
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Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation.
Int J Mol Sci
PUBLISHED: 05-03-2013
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IL-1?, a pro-inflammatory cytokine, has been shown to contribute to radiation injury. Sirt1, an NAD+-dependent class III protein deacetylase, plays an important role in the regulation of the proinflammatory cytokines involved in inflammation-associated diseases. The relationship between Sirt1 and IL-1?, however, has remained elusive. The present study was designed to explore the potential effect of Sirt1 on IL-1? expression induced by radiation and to provide a new target for the development of radiation protection drugs. Our results showed that radiation significantly increased IL-1? mRNA and protein expression and that pretreatment with resveratrol, a Sirt1 activator, inhibited the radiation-induced IL-1? expression in a concentration-dependent manner, whereas the knockdown or inhibition of Sirt1 by nicotinamide significantly enhanced radiation-induced IL-1? expression. This effect can likely be attributed to Sirt1-mediated inhibition of NLRP-3 inflammasome activation because Sirt1 inhibits the transactivation potential of NF-?b by deacetylation, which then suppresses NLRP3 transcription. Taken together, the results demonstrate that Sirt1 exerts anti-inflammatory effects by regulating NLRP3 expression partially through the NF-?b pathway in mesenchymal stem cells. More importantly, our findings suggest that resveratrol is an effective agent in protecting against radiation injury, and we provide a theoretical basis for developing a drug to protect against radiation injury by targeting Sirt1.
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Thrombocytopenia associated with 5-aminosalicylate prodrug, olsalazine: is the devil still there?
Int J Clin Pharm
PUBLISHED: 04-15-2013
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We present a case of a 63-year-old Chinese female who developed severe thrombocytopenia after receiving olsalazine 1.5 g daily for 3 months, and eventually culminated in hospital admission. According to a Medline search, this is the first case report of olsalazine-associated thrombocytopenia in Asia.
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Anti-noise algorithm of lidar data retrieval by combining the ensemble Kalman filter and the Fernald method.
Opt Express
PUBLISHED: 04-11-2013
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The lidar signal-to-noise ratio decreases rapidly with an increase in range, which severely affects the retrieval accuracy and the effective measure range of a lidar based on the Fernald method. To avoid this issue, an alternative approach is proposed to simultaneously retrieve lidar data accurately and obtain a de-noised signal as a by-product by combining the ensemble Kalman filter and the Fernald method. The dynamical model of the new algorithm is generated according to the lidar equation to forecast backscatter coefficients. In this paper, we use the ensemble sizes as 60 and the factor ?(1/2) as 1.2 after being weighed against the accuracy and the time cost based on the performance function we define. The retrieval and de-noising results of both simulated and real signals demonstrate that our method is practical and effective. An extensive application of our method can be useful for the long-term determining of the aerosol optical properties.
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Mercury distribution and speciation in different brain regions of beluga whales (Delphinapterus leucas).
Sci. Total Environ.
PUBLISHED: 03-29-2013
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The toxicokinetics of mercury (Hg) in key species of Arctic ecosystem are poorly understood. We sampled five brain regions (frontal lobe, temporal lobe, cerebellum, brain stem and spinal cord) from beluga whales (Delphinapterus leucas) harvested in 2006, 2008, and 2010 from the eastern Beaufort Sea, Canada, and measured total Hg (HgT) and total selenium (SeT) by inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer or cold vapor atomic absorption spectrometry, and the chemical forms using a high performance liquid chromatography ICP-MS. At least 14% of the beluga whales had HgT concentrations higher than the levels of observable adverse effect (6.0 mg kg(-1) wet weight (ww)) in primates. The concentrations of HgT differed between brain regions; median concentrations (mgkg(-1) ww) were 2.34 (0.06 to 22.6, 81) (range, n) in temporal lobe, 1.84 (0.12 to 21.9, 77) in frontal lobe, 1.84 (0.05 to 16.9, 83) in cerebellum, 1.25 (0.02 to 11.1, 77) in spinal cord and 1.32 (0.13 to 15.2, 39) in brain stem. Total Hg concentrations in the cerebellum increased with age (p<0.05). Between 35 and 45% of HgT was water-soluble, of which, 32 to 41% was methyl mercury (MeHg) and 59 to 68% was labile inorganic Hg. The concentration of MeHg (range: 0.03 to 1.05 mg kg(-1) ww) was positively associated with HgT concentration, and the percent MeHg (4 to 109%) decreased exponentially with increasing HgT concentration in the spinal cord, cerebellum, frontal lobe and temporal lobe. There was a positive association between SeT and HgT in all brain regions (p<0.05) suggesting that Se may play a role in the detoxification of Hg in the brain. The concentration of HgT in the cerebellum was significantly associated with HgT in other organs. Therefore, HgT concentrations in organs that are frequently sampled in bio-monitoring studies could be used to estimate HgT concentrations in the cerebellum, which is the target organ of MeHg toxicity.
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The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment.
Oncol Lett
PUBLISHED: 03-12-2013
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Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer.
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Glucose suppresses biological ferroelectricity in aortic elastin.
Phys. Rev. Lett.
PUBLISHED: 03-10-2013
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Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.
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Mesenchymal stem cells downregulate articular chondrocyte differentiation in noncontact coculture systems: implications in cartilage tissue regeneration.
Stem Cells Dev.
PUBLISHED: 02-15-2013
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While chondrogenesis of mesenchymal stem cells (MSCs) in vitro has been extensively studied, their participation in cartilage tissue repair remains unresolved. This study was designed to elucidate if MSCs affect the phenotype of articular chondrocytes (ACs). A combination of noncontact coculture modes was developed. Human or rabbit MSCs and rabbit ACs (rACs) were encapsulated in alginate hydrogel beads [three-dimensional (3D)] or cultured in a monolayer [two-dimensional (2D)] and subsequently cocultured in the Transwell(®) system. After coculture, cell morphology, growth, deposition of the cartilaginous extracellular matrix (ECM), and gene expression of rACs were investigated. It was found that upon coculture without a cell-cell contact, both 2D and 3D cultured MSCs dramatically induced the morphological transformation of 2D cultured rACs from round to a spindle-like shape, and however inhibited the generation of cellular aggregates of 3D cultured rACs. Most strikingly, a coculture resulted in a significantly less deposition of the cartilaginous ECM, including glycosaminoglycans and collagen type II by both 2D and 3D cultured rACs. Importantly, similar observations were achieved for rACs cultured in an MSC-conditioned medium, confirming the definite paracrine interactions between MSCs and rACs. Based on the analysis of gene expression, this phenotypic change of rACs was not identical as the dedifferentiation. To the best of our knowledge, this is a first study demonstrating that MSCs could downregulate chondrocytic differentiation of ACs and warrants considerations in cartilage tissue repair.
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Assessing and managing sediment contamination in transitional waters.
Environ Int
PUBLISHED: 02-08-2013
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Sediment contamination remains a global problem, particularly in transitional waters such as estuaries and coastal lagoons, which are the recipients of chemicals from multiple near- and far-field sources. Although transitional waters are highly productive ecosystems, approaches for assessing and managing their sediment contamination are not as well developed as in marine and fresh waters. Further, although transitional waters remain defined by their variable and unique natural water quality characteristics, particularly salinity, the biota inhabiting such ecosystems, once thought to be defined by Remanes "paradox of brackish water", are being redefined. The purpose of the present paper is to build on an earlier but now dated (>12years old) review of methods to assess sediment contamination in estuaries, extending this to all transitional waters, including information on integrative assessments and on management decision-making. The following are specifically discussed: chemical assessments; bioindicators; biomarkers; and, biological surveys. Assessment and management of sediment contamination in transitional waters need to be focused on ecosystem services and, where appropriate and possible, be proactive rather than reactive when uncertainty has been suitably reduced.
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Tat-SmacN7 induces radiosensitization in cancer cells through the activation of caspases and induction of apoptosis.
Int. J. Oncol.
PUBLISHED: 01-22-2013
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A major concern in cancer therapy is resistance of tumors such as human non-small cell lung cancer and esophageal cancer to radiotherapy. Intrinsic radioresistance of these cancer cells limits therapeutic ef?ciency. Here, we determined in two cancer cell lines the potential radiosensitizing activity of Tat-SmacN7, a small molecule compound, which mimics the activity of Smac, a mitochondrial protein released during apoptosis. We found that Tat-SmacN7 can enter the cells and promote RNA expression and the activity of caspase-3, -8 and -9 and sensitized the cancer cells to radiation with a sensitization enhancement ratio (SER) of 1.5-1.6. Tat-SmacN7 radiosensitization was mediated by both extrinsic and intrinsic apoptosis pathways through activation of caspases. Consistently, blockage of caspase activation, through treatment with a caspase inhibitor, z-VAD-fmk, inhibited apoptosis and abrogated Tat-SmacN7 radiosensitization. Our study demonstrates that Tat-SmacN7 also has radiosensitization effects in vivo, so it could be further developed as a novel class of radiosensitizers for the treatment of radioresistant human non-small cell lung cancer and esophageal cancer.
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2-(2-Methylfuran-3-carboxamido)-3-phenylpropanoic acid, a potential CYP26A1 inhibitor to enhance all-trans retinoic acid-induced leukemia cell differentiation based on virtual screening and biological evaluation.
Bioorg. Med. Chem.
PUBLISHED: 01-20-2013
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To develop new CYP26A1 inhibitors, a three-cycle virtual screening was carried out based on the constructed homology model of human CYP26A1 using Dock, Fred, Gold and AutoDock. Twenty-two compounds exhibited high scores and reasonable binding modes in molecular docking were purchased from Specs Company. Eighteen compounds were tested their abilities to enhance ATRA-induced differentiation in human acute promyelocytic leukemia NB4 cells. Eight of them enhanced the ability of ATRA to induce differentiation at concentrations of 0.5 and 1 ?M. Among these compounds, 2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid (S8) is of most effective in blocking ATRA breaking down in NB4 cells based on the LC-MS/MS assay.
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In vitro and in vivo evaluation of anisomycin against Ehrlich ascites carcinoma.
Oncol. Rep.
PUBLISHED: 01-03-2013
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Anisomycin eminently inhibits cell proliferation in vitro. The aim of this study was to explore the potential of anisomycin to treat tumors in vivo and its mechanism(s) of action. The results showed that peritumoral administration of anisomycin significantly suppressed Ehrlich ascites carcinoma (EAC) growth resulting in the survival of approximately 60% of the mice 90 days after EAC inoculation. Enhancement of infiltrating lymphocytes was noted in the tumor tissue, which was dramatically superior to adriamycin. The growth inhibitory rate of EAC cells was enhanced with increasing concentrations of anisomycin, following an enhanced apoptotic rate. The total apoptotic rate induced by 160 ng/ml of anisomycin was higher when compared to that induced by 500 ng/ml of adriamycin. DNA breakage and nanostructure changes were also noted in the EAC cells. The levels of caspase-3 mRNA, caspase-3 and cleaved-caspase-3 proteins in the anisomycin?treated EAC cells were augmented in a dose- and time-dependent manner, following the activation of caspase-8 and caspase-9, which finally triggered PARP cleavage. The cleaved-caspase-3, cleaved-caspase-8 and cleaved-caspase-9 proteins were mainly localized in the nuclei of the cells. These results indicate that anisomycin efficaciously represses in vitro and in vivo growth of EAC cells through caspase signaling, significantly superior to the effects of adriamycin. This suggests the potential of anisomycin for the treatment of breast cancer.
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Acculturation, Dietary Acceptability, and Diabetes Management among Chinese in North America.
Front Endocrinol (Lausanne)
PUBLISHED: 01-01-2013
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Immigrants to a new country face many challenges when diagnosed with type 2 diabetes, a chronic disease with a complex treatment involving both medical and behavioral interventions. These challenges will depend upon the extent to which the patient has adapted to the new countrys social and cultural norms, as well as individual factors such as age, education, and gender. This adaptation is termed acculturation. With respect to nutritional interventions for type 2 diabetes, uptake and adherence over the long term will depend upon overall health literacy, the cultural acceptability of the recommended diet. This review has focused on acculturation and its effects on diabetes management in ethnic Chinese in North America as an example of one populous minority and the challenges faced in adopting nutritional recommendations. Research directions and practical considerations are suggested.
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Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice.
Int J Nanomedicine
PUBLISHED: 01-01-2013
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Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles.
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The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury.
PLoS ONE
PUBLISHED: 01-01-2013
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The acute and residual (or long-term) bone marrow (BM) injury induced by ionizing radiation (IR) is a major clinic concern for patients receiving conventional radiotherapy and victims accidentally exposed to a moderate-to-high dose of IR. In this study, we investigated the effects of the treatment with the p38 inhibitor SB203580 (SB) and/or granulocyte colony-stimulating factor (G-CSF) on the hematoimmune damage induced by IR in a mouse model. Specifically, C57BL/6 mice were exposed to a sublethal dose (6 Gy) of total body irradiation (TBI) and then treated with vehicle, G-CSF, SB, and G-CSF plus SB. G-CSF (1 µg/mouse) was administrated to mice by intraperitoneal (ip) injection twice a day for six successive days; SB (15 mg/kg) by ip injection every other day for 10 days. It was found that the treatment with SB and/or G-CSF significantly enhanced the recovery of various peripheral blood cell counts and the number of BM mononuclear cells 10 and 30 days after the mice were exposed to TBI compared with vehicle treatment. Moreover, SB and/or G-CSF treatment also increased the clonogenic function of BM hematopoietic progenitor cells (HPCs) and the frequency of BM lineage -Sca1+c-kit+ cells (LSK cells) and short-term and long term hematopoietic stem cells (HSCs) 30 days after TBI, in comparison with vehicle treated controls. However, the recovery of peripheral blood B cells and CD4+ and CD8+ T cells was not significantly affected by SB and/or G-CSF treatment. These results suggest that the treatment with SB and/or G-CSF can reduce IR-induced BM injury probably in part via promoting HSC and HPC regeneration.
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Simple multiscale algorithm for layer detection with lidar.
Appl Opt
PUBLISHED: 12-24-2011
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Lidar is a powerful active remote sensing device used in the detection of the optical properties of aerosols and clouds. However, there are difficulties in layer detection and classification. Many previous methods are too complex for large dataset analysis or limited to data with too high a signal-to-noise ratio (SNR). In this study, a mechanism of multiscale detection and overdetection rejection is proposed based on a trend index function that we define. Finally, we classify layers based on connected layers employing a quantity known as the threshold of the peak-to-base ratio. We find good consistency between retrieved results employing our method and visual analysis. The testing of synthetic signals shows that our algorithm performs well with SNRs higher than 4. The results demonstrate that our algorithm is simple, practical, and suited to large dataset applications.
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In vivo toxicological evaluation of Anisomycin.
Toxicol. Lett.
PUBLISHED: 08-22-2011
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Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus. Recent studies have shown that Anisomycin as a novel immunosuppressive agent is superior to Cyclosporine A (J. Immunother. 31, 858-870, 2008). In order to make toxicological evaluation of Anisomycin, acute and four-week continuously intravenous toxicity studies were performed in mice. IC(50) value tested on peripheral lymphocytes was 25.44 ng/ml. The calculated LD(50) for Anisomycin was 119.64 mg/kg. The mice were intravenously injected through mouse tail vein with a total dose of 5, 15, 30 and 60 mg/kg/mice of Anisomycin every other day for 4 weeks. Just in the high-dose mice, death of three mice happened and body weight of the mice was significantly decreased. Statistically significant changes in organ index included increases in ratios of the spleen, liver, lung and brain to the body weight, and decrease in ratio of the thymus to the body weight. Changes in clinical biochemistry parameters included increases in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and decreases in the glucose (GLU) activity. The distinct inflammation appeared in the lung, liver and kidney, and the number and size of megakaryocytes in the spleen were significantly increased. Anisomycin did not induce formation of the peripheral blood micronucleus, but increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm aberrations. However, the above aberrant changes occurred only in the mice treated with the high-dose Anisomycin. These results indicate that although Anisomycin has no significant side effects at effectively therapeutic doses, its over-dosage may lead to toxicity, particularly pulmo-, nephro- and hepato-toxicity.
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How does climate change influence Arctic mercury?
Sci. Total Environ.
PUBLISHED: 07-18-2011
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Recent studies have shown that climate change is already having significant impacts on many aspects of transport pathways, speciation and cycling of mercury within Arctic ecosystems. For example, the extensive loss of sea-ice in the Arctic Ocean and the concurrent shift from greater proportions of perennial to annual types have been shown to promote changes in primary productivity, shift foodweb structures, alter mercury methylation and demethylation rates, and influence mercury distribution and transport across the ocean-sea-ice-atmosphere interface (bottom-up processes). In addition, changes in animal social behavior associated with changing sea-ice regimes can affect dietary exposure to mercury (top-down processes). In this review, we address these and other possible ramifications of climate variability on mercury cycling, processes and exposure by applying recent literature to the following nine questions; 1) What impact has climate change had on Arctic physical characteristics and processes? 2) How do rising temperatures affect atmospheric mercury chemistry? 3) Will a decrease in sea-ice coverage have an impact on the amount of atmospheric mercury deposited to or emitted from the Arctic Ocean, and if so, how? 4) Does climate affect air-surface mercury flux, and riverine mercury fluxes, in Arctic freshwater and terrestrial systems, and if so, how? 5) How does climate change affect mercury methylation/demethylation in different compartments in the Arctic Ocean and freshwater systems? 6) How will climate change alter the structure and dynamics of freshwater food webs, and thereby affect the bioaccumulation of mercury? 7) How will climate change alter the structure and dynamics of marine food webs, and thereby affect the bioaccumulation of marine mercury? 8) What are the likely mercury emissions from melting glaciers and thawing permafrost under climate change scenarios? and 9) What can be learned from current mass balance inventories of mercury in the Arctic? The review finishes with several conclusions and recommendations.
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Methylmercury and selenium speciation in different tissues of beluga whales (Delphinapterus leucas) from the western Canadian Arctic.
Environ. Toxicol. Chem.
PUBLISHED: 06-29-2011
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Monitoring data have shown that the total monomethylmercury (CH(3) Hg(+) and its complexes; collectively referred as MeHg hereafter) concentrations in Arctic marine mammals have remained very high in recent decades. Toward a better understanding of the metabolic and toxicological implications of these high levels of MeHg, we report here on the molecular forms of MeHg in the muscle, brain, liver, and kidneys of 10 beluga whales from the western Canadian Arctic. In all tissues analyzed, monomethylmercury was found to be dominated by methylmercuric cysteinate, a specific form of MeHg believed to be able to transport across the blood-brain barrier. Another MeHg-thiol complex, methylmercuric glutathionate, was also detected in the muscle and, to a much lesser extent, in the liver and brain tissues. Furthermore, a profound inorganic Hg peak was detected in the liver and brain tissues, which showed the same retention time as a selenium (Se) peak, suggesting the presence of an Hg-Se complex, most likely an inorganic Hg complex with a selenoamino acid. These results provide the first analytical support that the binding of MeHg with glutathione and Se may have protected beluga whales from the toxic effect of high concentrations of MeHg in their body.
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Multiferroic CoFe2O4-Pb(Zr(0.52)Ti(0.48))O3 core-shell nanofibers and their magnetoelectric coupling.
Nanoscale
PUBLISHED: 06-03-2011
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Multiferroic CoFe(2)O(4)-Pb(Zr(0.52)Ti(0.48))O(3) core-shell nanofibers have been synthesized by coaxial electrospinning in combination with a sol-gel process. The core-shell configuration of nanofibers has been verified by scanning electron microscopy and transmission electron microscopy, and the spinel structure of CoFe(2)O(4) and perovskite structure of Pb(Zr(0.52)Ti(0.48))O(3) have been confirmed by X-ray diffraction and selected area electron diffraction. The multiferroic properties of core-shell nanofibers have been demonstrated by magnetic hysteresis and piezoresponse force microscopy, and their magnetoelectric coupling has been confirmed by evolution of piezoresponse under an external magnetic field, showing magnetically induced ferroelectric domain switching and changes in switching characteristics. The lateral magnetoelectric coefficient is estimated to be 2.95 × 10(4) mV/cmOe, two orders of magnitude higher than multiferroic thin films of similar composition.
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Hypoxia-induced ?-catenin downregulation involves p53-dependent activation of Siah-1.
Cancer Sci.
PUBLISHED: 05-12-2011
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Solid tumors contain extensive hypoxic areas and it is of considerable importance to decipher the potential role of hypoxia in signaling pathway regulation. In the present study, we examined the impact of hypoxia on ?-catenin status and the mechanisms involved. Hypoxia significantly decreased ?-catenin protein, but had no effect on glycogen synthase kinase (GSK)-3? or adenomatous polyposis coli (APC) levels. However, hypoxia-induced ?-catenin downregulation seemed to require APC but not GSK-3?. Further investigation revealed that hypoxia significantly upregulated Siah-1, the human homolog of Drosophila seven in absentia. In addition, hypoxia augmented the interaction between ?-catenin and SIP and Skp1. Silencing of Siah-1, as well as the use of a dominant negative Siah-1 mutant, attenuated these responses to hypoxia and rescued ?-catenin transactivation. The Siah-1-mediated degradation of ?-catenin during hypoxia may involve p53, but not hypoxia-inducible factor-1, activation. Together, the results suggest that hypoxia downregulates ?-catenin by increasing Siah-1 expression in a p53-dependent manner.
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Comparison of immature and mature bone marrow-derived dendritic cells by atomic force microscopy.
Nanoscale Res Lett
PUBLISHED: 03-06-2011
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A comparative study of immature and mature bone marrow-derived dendritic cells (BMDCs) was first performed through an atomic force microscope (AFM) to clarify differences of their nanostructure and adhesion force. AFM images revealed that the immature BMDCs treated by granulocyte macrophage-colony stimulating factor plus IL-4 mainly appeared round with smooth surface, whereas the mature BMDCs induced by lipopolysaccharide displayed an irregular shape with numerous pseudopodia or lamellapodia and ruffles on the cell membrane besides becoming larger, flatter, and longer. AFM quantitative analysis further showed that the surface roughness of the mature BMDCs greatly increased and that the adhesion force of them was fourfold more than that of the immature BMDCs. The nano-features of the mature BMDCs were supported by a high level of IL-12 produced from the mature BMDCs and high expression of MHC-II on the surface of them. These findings provide a new insight into the nanostructure of the immature and mature BMDCs.
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Macrocyclic chelator assembled RGD multimers for tumor targeting.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-24-2011
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Macrocyclic chelators have been extensively used for complexation of metal ions. A widely used chelator, DOTA, has been explored as a molecular platform to assemble multiple bioactive peptides in this paper. The multivalent DOTA-peptide bioconjugates demonstrate promising tumor targeting ability.
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Individually integrated traditional Chinese medicine approach in the management of knee osteoarthritis: study protocol for a randomized controlled trial.
Trials
PUBLISHED: 02-08-2011
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Knee osteoarthritis (OA) is considered a major public health issue causing chronic disability worldwide with the increasing number of aging people. In China and increasingly worldwide, many sufferers with knee OA are using complementary and alternative medicine including herbal drug, herbal patch, acupuncture and Tuina etc., to alleviate their symptoms. However, evidence gathered from systematic reviews or randomized controlled trials (RCT) has only validated acupuncture for the management of osteoarthritic pain. Moreover, such Traditional Chinese Medicine (TCM) methods above are commonly used in an integrative way. This trial is aimed to compare the efficacy of an individually integrated TCM approach in the management of knee OA with other single treatments as parallel randomized controls.
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Mercury distribution and transport across the ocean-sea-ice-atmosphere interface in the Arctic Ocean.
Environ. Sci. Technol.
PUBLISHED: 02-02-2011
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The Arctic sea-ice environment has been undergoing dramatic changes in the past decades; to which extent this will affect the deposition, fate, and effects of chemical contaminants remains virtually unknown. Here, we report the first study on the distribution and transport of mercury (Hg) across the ocean-sea-ice-atmosphere interface in the Southern Beaufort Sea of the Arctic Ocean. Despite being sampled at different sites under various atmospheric and snow cover conditions, Hg concentrations in first-year ice cores were generally low and varied within a remarkably narrow range (0.5-4 ng L(-1)), with the highest concentration always in the surface granular ice layer which is characterized by enriched particle and brine pocket concentration. Atmospheric Hg depletion events appeared not to be an important factor in determining Hg concentrations in sea ice except for frost flowers and in the melt season when snowpack Hg leaches into the sea ice. The multiyear ice core showed a unique cyclic feature in the Hg profile with multiple peaks potentially corresponding to each ice growing/melting season. The highest Hg concentrations (up to 70 ng L(-1)) were found in sea-ice brine and decrease as the melt season progresses. As brine is the primary habitat for microbial communities responsible for sustaining the food web in the Arctic Ocean, the high and seasonally changing Hg concentrations in brine and its potential transformation may have a major impact on Hg uptake in Arctic marine ecosystems under a changing climate.
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Constitutive activation of the thyroid-stimulating hormone receptor (TSHR) by mutating Ile691 in the cytoplasmic tail segment.
PLoS ONE
PUBLISHED: 01-21-2011
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Autosomal dominant non-autoimmune hyperthyroidism (ADNAH) is a rare genetic disorder of the endocrine system. Molecular genetic studies in ADNAH have revealed heterozygous germline mutations in the TSHR. To data, mutations leading to an increase in the constitutive activation of the TSHR have been described in the transmembrane segments, exoloops and cytoplasmic loop of TSHR. These mutations result in constitutive activation of the G(?s)/cAMP or G(?q/11)/inositol phosphate (IP) pathways, which stimulate thyroid hormone production and thyroid proliferation.
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Analysis of neural interaction in motor cortex during reach-to-grasp task based on Dynamic Bayesian Networks.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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In this work, we took the analysis of neural interaction based on the data recorded from the motor cortex of a monkey, when it was trained to complete multi-targets reach-to-grasp tasks. As a recently proved effective tool, Dynamic Bayesian Network (DBN) was applied to model and infer interactions of dependence between neurons. In the results, the gained networks of neural interactions, which correspond to different tasks with different directions and orientations, indicated that the target information was not encoded in simple ways by neuronal networks. We also explored the difference of neural interactions between delayed period and peri-movement period during reach-to-grasp task. We found that the motor control process always led to relatively more complex neural interaction networks than the plan thinking process.
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Partitioning and localization of environment-sensitive 2-(2-pyridyl)- and 2-(2-pyrimidyl)-indoles in lipid membranes: a joint refinement using fluorescence measurements and molecular dynamics simulations.
J Phys Chem B
PUBLISHED: 10-08-2010
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Fluorescence of environment-sensitive dyes is widely applied to monitor local structure and solvation dynamics of biomolecules. It has been shown that, in comparison with a parent indole fluorophore, fluorescence of 2-(2-pyridyl)-5-methylindole (5M-PyIn-0) and 2-[2-(4,6-dimethylpyrimidyl)]-indole (DMPmIn-0) is remarkably sensitive to hydrogen bonding with protic partners. Strong fluorescence, observed for these compounds in nonpolar and polar aprotic solvents, is efficiently quenched in aqueous solution. This study demonstrates that 5M-PyIn-0 and DMPmIn-0, which are almost nonemitting in aqueous solution, become highly fluorescent upon titrating with phospholipid vesicles. The fluorescence enhancement is accompanied by a significant blue shift of emission maximum. The Gibbs free energy of membrane partitioning, measured by the increase in the steady-state fluorescence intensities during transfer from an aqueous environment to a lipid bilayer, is very favorable for both compounds, being in a range from -7.1 to -8.0 kcal/mol and depending only slightly on lipid composition of the membrane. The fluorescence enhancement upon membrane partitioning is indicative of the loss of the specific hydrogen-bonding interactions between the excited fluorophore and water molecules, causing efficient fluorescence quenching in bulk water. This conclusion is supported by atomistic molecular dynamics (MD) simulations, demonstrating that both 5M-PyIn-0 and DMPmIn-0 bind rapidly and partition deeply into a lipid bilayer. MD simulations also show a rapid, nanosecond-scale decrease in the probability of solute-solvent hydrogen bonding during passive diffusion of the probe molecules from bulk water into a lipid bilayer. At equilibrium conditions, both 5M-PyIn-0 and DMPmIn-0 prefer deep localization within the hydrophobic, water-free region of the bilayer. A free energy profile of penetration across a bilayer estimated using MD umbrella sampling shows that both indole derivatives favor residence in a rather wide potential energy well located 10-15 Å from the bilayer center.
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The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study.
Environ Health
PUBLISHED: 08-15-2010
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A community in northern Italy was previously reported to have an excess incidence of amyotrophic lateral sclerosis among residents exposed to high levels of inorganic selenium in their drinking water.
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Natural and anthropogenic mercury distribution in marine sediments from Hudson Bay, Canada.
Environ. Sci. Technol.
PUBLISHED: 07-13-2010
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Twelve marine sediment cores from Hudson Bay, Canada, were collected to investigate the response of sub-Arctic marine sediments to atmospherically transported anthropogenic mercury (Hg). Modeling by a two-layer sediment mixing model suggests that the historical Hg deposition to most of the sediment cores reflects the known history of atmospheric Hg deposition in North America, with an onset of increasing anthropogenic Hg emissions in the late 1800s and early 1900s and a reduction of Hg deposition in the mid- to late-1900s. However, although anthropogenic Hg has contributed to a ubiquitous increase in Hg concentrations in sediments over the industrial era, the most elevated industrial-era sedimentary Hg concentrations only marginally exceed the upper preindustrial sedimentary Hg concentrations. Analysis of delta13C and relationship between Hg and organic matter capture suggests that the response of Hudson Bay sediments to changes in atmospheric Hg emissions is largely controlled by the particle flux in the system and that natural changes in organic matter composition and dynamics can cause variation in sedimentary Hg concentrations at least to the same extent as those caused by increasing anthropogenic Hg emissions.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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