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Find video protocols related to scientific articles indexed in Pubmed.
Influence of atmospheric turbulence on the transmission of orbital angular momentum for Whittaker-Gaussian laser beams.
Opt Express
PUBLISHED: 10-17-2014
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We analyze the effects of turbulence on the detection probability spectrum and the mode weight of the orbital angular momentum (OAM) for Whittaker-Gaussian (WG) laser beams in weak non-Kolmogorov turbulence channels. Our numerical results show that WG beam is a better light source for mitigating the effects of turbulence with several adjustable parameters. The real parameters of WG beams ? and W0, which have significant effects on the mode weight, have no influence on the detection probability spectrum. Larger signal OAM quantum number, shorter wavelength, smaller beamwidth and coherence length will lead to the lower detection probability of the signal OAM mode.
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Application of immunosuppressant facilitates the therapy of optic neuritis combined with Sjögren's syndrome.
Chin. Med. J.
PUBLISHED: 09-06-2014
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Optic neuritis (ON) is often the first symptom of multiple sclerosis (MS) and neuromyelitis optica (NMO) while there has been very little research reported on ON combined with Sjögren's syndrome (SS). The aim of this study is to provide different treatments and services for and NMO patients combined with SS.
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Characterization of macular thickness changes in Leber's hereditary optic neuropathy by optical coherence tomography.
BMC Ophthalmol
PUBLISHED: 09-01-2014
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To characterize macular thickness (MT) changes in Leber's hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA).
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A low level of GPR37 is associated with human hepatocellular carcinoma progression and poor patient survival.
Pathol. Res. Pract.
PUBLISHED: 08-09-2014
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GPR37, also known as parkin-associated endothelin-like receptor (Pael-R), is an orphan G protein-coupled receptor (GPCR). It has been reported that GPCRs play vital roles in the development and progression of cancer. To investigate the potential roles of GPR37 in hepatocellular carcinoma (HCC), expression of GPR37 was examined in human HCC samples. Immunohistochemistry and Western blot analyses were performed for GPR37 in 57 hepatocellular carcinoma samples. GPR37 expression was low in hepatocellular carcinoma as compared with the adjacent non-tumorous tissues. Clinicopathological analysis showed that GPR37 expression was significantly correlated with histological grade and the level of alpha fetal protein (AFP) (P=0.000 and 0.002, respectively). The Kaplan-Meier survival curves revealed that decreasing GPR37 expression was associated with poor prognosis in HCC patients, while in vitro, following the release from serum starvation of HuH7 HCC cell, the expression of GPR37 was downregulated. In addition, the transient GPR37 knockdown by siRNA in HuH7 cells significantly decreased the apoptosis of hepatoma cells with activation of the phosphatidylinositol 3-kinase-Akt signaling pathway. Our data suggest that GPR37 may play an important role in the pathogenesis of hepatocellular carcinoma by affecting the proliferation of H CC cells, and it could be a novel potential molecular therapy target for HCC.
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Estrogen prevents high-glucose-induced damage of retinal ganglion cells via mitochondrial pathway.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 08-04-2014
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Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults. Previous research has shown that the apoptosis of retinal ganglion cells(RGCs) plays an important role in the initiation and development of diabetic retinopathy. The positive effect of estrogen on the nervous system is currently attracting increasing attention. In this study, we investigated whether17?-estradiolum (E2) has protective effects on RGCs in a high-glucose environment.
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Identification of Gem as a new candidate prognostic marker in hepatocellular carcinoma.
Pathol. Res. Pract.
PUBLISHED: 07-17-2014
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GTP binding protein overexpressed in skeletal muscle (Gem) is a Ras-related protein whose expression is induced in several cell types upon activation by extracellular stimuli. To investigate the potential roles of Gem in hepatocellular carcinoma (HCC), expression of Gem was examined in human HCC samples. Western blot analysis showed that compared with primary human hepatocytes and adjacent noncancerous tissue, significant down-regulation of Gem was found in HCC cells and tumor tissues. In addition, immunohistochemical analysis of Gem expression was investigated in 108 specimens of HCC tissues. Clinicopathological data were collected to analyze the association with Gem expression. Expression of Gem was significantly negatively correlated with histological grade (P=0.001), tumor size (P=0.020), and vascular invasion (P=0.005), and Gem was also negatively correlated with proliferation marker Ki-67 (P<0.01). More importantly, the Kaplan-Meier survival curves analysis revealed that low expression of Gem was associated with poor prognosis in HCC patients. Univariate analysis showed that Gem expression was associated with poor prognosis (P=0.006). Multivariate analysis indicated that Gem expression was an independent prognostic marker for HCC (P=0.007). Finally, serum starvation and release experiments showed that Gem expression was negatively related with cell proliferation. In the conclusion, our results suggested that down regulation of Gem expression was involved in the pathogenesis of hepatocellular carcinoma, and it might be a favorable independent prognostic parameter for HCC.
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Magnetic Resonance Lymphangiography for the Study of Lymphatic System in Lymphedema.
J Reconstr Microsurg
PUBLISHED: 07-15-2014
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Background?Imaging of the lymphatic system is difficult because of its structural and anatomical characteristics, and the conventional diagnostic method, radionuclide-based imaging, has the disadvantage of poor resolution. Magnetic resonance (MR) imaging has been shown the capability of depicting lymphatic channels in lymphedema recently. The purpose of this study was to evaluate the imaging of MR lymphangiography (MRL) in diagnosis of limb lymphedema and its possible role in the microsurgical management of lymphedema. Methods?A total of 710 patients with primary lymphedema (n?=?378), secondary lymphedema (n?=?332), were enrolled in the study. Contrast-enhanced lymphangiography was performed with 3.0 T MR unit (Philips Medical Systems, Best, The Netherlands) after intracutaneously injection of gadobenate dimeglumine. Kinetic of enhanced lymph flow within lymphatics and lymph nodes as well as the morphological abnormalities of lymphatic system were evaluated. Results?MRL was able to display the detailed anatomical changes in the vessels and nodes. In primary lymphedema, there are three major types of lymphatic system malformation: (1) only lymph nodes affected, (2) only lymph vessels affected, and (3) both lymph vessels and lymph nodes affected. In secondary lymphedema MRL clearly demonstrated tortuous and dilated collecting lymphatics in lymphedemtous limbs. MRL also provided information concerning the functional status of lymph transport in lymphatic vessels and nodes by real-time visualization of enhanced lymph flow in lymphatic channels and within lymph nodes. Conclusion?Contrast MRL was capable of evaluating the anatomical and functional status of lymphatic vessels and lymph nodes in lymphedematous limb. This new imaging shows good potential for use in the diagnosis and surgical management of lymphedema.
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Photopatterning of Multifunctional Hydrogels to Direct Adult Neural Precursor Cells.
Adv Healthc Mater
PUBLISHED: 07-10-2014
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Matrix-metalloproteinase and photosensitive peptide units are combined with heparin and poly(ethylene glycol) into a light-sensitive multicomponent hydrogel material. Localized degradation of the hydrogel matrix allows the creation of defined spatial constraints and adhesive patterning for cells grown in culture. Using this matrix system, it is demonstrated that the degree of confinement determines the fate of neural precursor cells in vitro.
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ABO blood group and esophageal carcinoma risk: from a case-control study in Chinese population to meta-analysis.
Cancer Causes Control
PUBLISHED: 07-10-2014
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The association between ABO blood group and the risk of esophageal carcinoma (EC) in previously published studies is uncertain and conflicting. The aim of the current study was to determine the correlation of ABO blood group with EC risk via a case-control study and meta-analysis.
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Average capacity for optical wireless communication systems over exponentiated Weibull distribution non-Kolmogorov turbulent channels.
Appl Opt
PUBLISHED: 07-01-2014
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We model the average channel capacity of optical wireless communication systems for cases of weak to strong turbulence channels, using the exponentiation Weibull distribution model. The joint effects of the beam wander and spread, pointing errors, atmospheric attenuation, and the spectral index of non-Kolmogorov turbulence on system performance are included. Our results show that the average capacity decreases steeply as the propagation length L changes from 0 to 200 m and decreases slowly down or tends to a stable value as the propagation length L is greater than 200 m. In the weak turbulence region, by increasing the detection aperture, we can improve the average channel capacity and the atmospheric visibility as an important issue affecting the average channel capacity. In the strong turbulence region, the increase of the radius of the detection aperture cannot reduce the effects of the atmospheric turbulence on the average channel capacity, and the effect of atmospheric visibility on the channel information capacity can be ignored. The effect of the spectral power exponent on the average channel capacity in the strong turbulence region is higher than weak turbulence region. Irrespective of the details determining the turbulent channel, we can say that pointing errors have a significant effect on the average channel capacity of optical wireless communication systems in turbulence channels.
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A repertoire of peptide tags for controlled drug release from injectable noncovalent hydrogel.
Biomacromolecules
PUBLISHED: 05-21-2014
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A repertoire of conjugable tags for controlling the release of drugs from biomaterials is highly interesting for the development of combinatorial drug administration techniques. This paper describes such a system of 11 peptide tags derived from our previous work on a physical hydrogel system cross-linked through peptide-heparin interactions. The release kinetics of the tags correlate well with their affinity to heparin and obey Fick's second law of diffusion, with the exception of the ATIII peptide, which displays a stable release profile close to a zero-order reaction. A system for release experiments over seven months was built, using the hydrogel matrix as a barrier between the reservoirs of tagged compounds and supernatant. The gel matrix can be injected without affecting the releasing properties. A tagged cyclosporin A derivative was also tested, and its release was monitored by measuring its biological activity. This work represents a design of biomaterials with an integral system of drug delivery, where both the assembly process of the matrix and affinity capture/release of tagged compounds are based on the noncovalent interaction of heparin with one class of peptides.
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Probability density of the orbital angular momentum mode of Hankel-Bessel beams in an atmospheric turbulence.
Opt Express
PUBLISHED: 04-11-2014
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We develop a novel model of the probability density of the orbital angular momentum (OAM) modes for Hankel-Bessel beams in paraxial turbulence channel based on the Rytov approximation. The results show that there are multi-peaks of the mode probability density along the radial direction. The peak position of the mode probability density moves to beam center with the increasing of non-Kolmogorov turbulence-parameters and the generalized refractive-index structure parameters and with the decreasing of OAM quantum number, propagation distance and wavelength of the beams. Additionally, larger OAM quantum number and smaller non-Kolmogorov turbulence-parameter can be selected in order to obtain larger mode probability density. The probability density of the OAM mode crosstalk is increasing with the decreasing of the quantum number deviation and the wavelength. Because of the focusing properties of Hankel-Bessel beams in turbulence channel, compared with the Laguerre-Gaussian beams, Hankel-Bessel beams are a good light source for weakening turbulence spreading of the beams and mitigating the effects of turbulence on the probability density of the OAM mode.
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Abnormal expression of EMT-related proteins, S100A4, vimentin and E-cadherin, is correlated with clinicopathological features and prognosis in HCC.
Med. Oncol.
PUBLISHED: 03-24-2014
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We determined the expression of epithelial-mesenchymal transition (EMT) indicator proteins, E-cadherin (E-cad), vimentin (VIM), mucin 1 (MUC1) and S100 calcium-binding protein A4 (S100A4) in hepatocellular carcinoma (HCC) patient tissue samples. We also investigated the relationship between the expression of these proteins and clinicopathologic factors in HCC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in HCC patients. The expression of E-cad, VIM, MUC1 and S100A4 EMT indicator proteins was assessed in tissue microarray HCC tissue sections and corresponding peritumoral normal tissues by immunohistochemistry. In addition, the expression for the four EMT indicator proteins was correlated with clinicopathological features of HCC and patient outcome. Comparison of clinicopathological characteristics and immunohistochemistry by ?(2) analysis revealed that downregulation of E-cad in HCC was significantly associated with later TNM cancer stage (P = 0.012), gross classification (P = 0.018), regional lymph node metastasis (P = 0.036) and liver cirrhosis (P = 0.028). Increased S100A4 expression in HCC was significantly associated with differentiation (P = 0.032), tumor with a complete fibrous capsule (P = 0.031) and portal vein invasion (P = 0.038). High VIM expression in HCC was significantly associated with high serum ?-fetoprotein levels (P = 0.016). We also observed that low E-cad expression was significantly associated with overexpression of VIM (P = 0.001). Kaplan-Meier survival and Cox regression analysis revealed that low E-cad expression (HR = 0.164, 95 % CI 0.072 to 0.373, P < 0.001) and high serum ?-fetoprotein levels (HR = 2.202, 95 % CI 1.054 to 4.598, P = 0.036) were independent prognostic factors in HCC. Our study demonstrates that high S100A4 and VIM expression and low E-cad expression correlate with an aggressive, malignant phenotype in HCC. These results also support a role for E-cad as a prognostic factor in HCC.
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Identification of UshA as a major enzyme for NAD degradation in Escherichia coli.
Enzyme Microb. Technol.
PUBLISHED: 03-01-2014
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Nicotinamide adenine dinucleotide (NAD) and its reduced form NADH are essential cofactors for many redox biocatalysts. Because these cofactors are consumed in stoichiometric amounts, whole-cell biocatalysts have been routinely employed in order to reduce the costs. To further improve the efficacy of redox biocatalysts, it is essential to maintain the stability of nicotinamide cofactors, for which it is attractive to block degradation pathways for NAD(H). While the biosynthesis of NAD(H) has been well studied, it is less understood how NAD(H) are degraded. Here we demonstrated that UshA was a major periplasmic enzyme for NAD degradation in Escherichia coli. Purified recombinant UshA showed high pyrophosphatase activity with the catalytic efficiencies for hydrolysis of NAD and NADH at 3.7?M(-1)s(-1) and 1.4?M(-1)s(-1), respectively. Deletion of the ushA gene from the chromosome led to faster cell growth and improved extracellular NAD stability by 3-fold under conditions similar to whole-cell biocatalysis. These results significantly enriched our understanding on NAD metabolism, and should facilitate many applications including designing more robust redox biocatalysts.
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Increased expression of glycinamide ribonucleotide transformylase is associated with a poor prognosis in hepatocellular carcinoma, and it promotes liver cancer cell proliferation.
Hum. Pathol.
PUBLISHED: 02-28-2014
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Glycinamide ribonucleotide transformylase (GART) is a folate-dependent enzyme in the de novo purine pathway that has been the target of antineoplastic intervention for almost 2 decades. Until now, its expression and functional significance in hepatocellular carcinoma (HCC) have been unclear. We demonstrated by Western blotting that the expression of GART was markedly up-regulated in HCC patients. Immunohistochemistry staining was used to determine the expression of GART in HCC and adjacent nontumor tissues from 96 patients. Increased expression of GART correlated positively with the histologic grade (P = .001), tumor size (P = .043), number of tumorous nodes (P = .020), and intrahepatic metastases (P = .031), suggesting a role for GART in the progression of HCC. Patients with higher GART expression had a much worse overall survival rate than those with low expression (P = .002). Furthermore, multivariate analysis showed that GART expression was an independent predictor of overall survival (hazard ratio, 2.265; 95% confidence interval, 1.335-3.842; P = .002). Depletion of GART by small interfering RNA inhibited cell proliferation and blocked S-phase and mitotic entry in cultured HepG2 and BEL-7404 cells. Western blot analyses showed that GART depletion decreased the proliferating cell nuclear antigen concentration. Collectively, our clinical and in vitro data indicate that GART expression may be one of the causative factors for a poor prognosis in HCC.
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Identification of novel small molecule modulators of K2P18.1 two-pore potassium channel.
Eur. J. Pharmacol.
PUBLISHED: 01-30-2014
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Two-pore domain potassium (K2P) channels are responsible for background potassium (K+) current, which is crucial for the maintenance of resting membrane potential. K2P18.1, also called TWIK-related spinal cord K+ channel (TRESK) or KCNK18, is thought to be a major contributor to background K+ currents, particularly in sensory neurons where it is abundantly expressed. Despite its critical role and potential therapeutic implication, pharmacological tools for probing K2P18.1 activity remain unavailable. Here, we report a high-throughput screen against a collection of bioactive compounds that yielded 26 inhibitors and 8 activators of K2P18.1 channel activity with more than 10-fold selectivity over the homologous channel K2P9.1. Among these modulators, the antihistamine loratadine inhibited K2P18.1 activity with IC50 of 0.49±0.23 µM and is considerably more potent than existing K2P18.1 inhibitors. Importantly, the inhibition by loratadine remains equally efficacious upon potentiation of K2P18.1 by calcium signaling. Furthermore, the loratadine effect is dependent on transmembrane residues F145 and F352, providing orthogonal evidence that the inhibition is caused by a direct compound-channel interaction. This study reveals new pharmacological modulators of K2P18.1 activity useful in dissecting native K2P18.1 function.
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Calcineurin regulates coordinated outgrowth of zebrafish regenerating fins.
Dev. Cell
PUBLISHED: 01-21-2014
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Vertebrates develop organs and appendages in a proportionally coordinated manner, and animals that regenerate them do so to the same dimensions as the original structures. Coordinated proportional growth involves controlled regulation between allometric and isometric growth programs, but it is unclear what executes this control. We show that calcineurin inhibition results in continued allometric outgrowth of regenerating fins beyond their original dimensions. Calcineurin inhibition also maintains allometric growth of juvenile fins and induces it in adult fins. Furthermore, calcineurin activity is low when the regeneration rate is highest, and its activity increases as the rate decreases. Growth measurements and morphometric analysis of proximodistal asymmetry indicate that calcineurin inhibition shifts fin regeneration from a distal growth program to a proximal program. This shift is associated with the promotion of retinoic acid signaling. Thus, we identified a calcineurin-mediated mechanism that operates as a molecular switch between position-associated isometric and allometric growth programs.
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Characterization of retinal nerve fiber layer thickness changes associated with Leber's hereditary optic neuropathy by optical coherence tomography.
Exp Ther Med
PUBLISHED: 01-08-2014
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In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber's hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ?3 months; group 2, 4-6 months; group 3, 7-9 months; group 4, 10-12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness.
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Chaperonin containing TCP1, subunit 8 (CCT8) is upregulated in hepatocellular carcinoma and promotes HCC proliferation.
APMIS
PUBLISHED: 01-02-2014
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The development of molecular pathogenesis of hepatocellular carcinoma (HCC) is complex and involves alterations in the expression and conformation of assorted oncoproteins and tumor suppressors. Chaperonin containing TCP1 (CCT) is a cytolic molecular chaperone complex that is required for the correct folding of numerous proteins. In this study, we investigated a possible involvement of CCT subunit 8 (CCT8) in HCC development. Immunohistochemical analysis was performed in 102 human HCC samples. High CCT8 expression was detected in clinical HCC samples compared with adjacent noncancerous tissues. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. Western blot confirmed the high expression of CCT8 in HCC compared with adjacent normal tissue. Moreover, the biological significance of the aberrant expression of CCT8 was investigated in HCC cell lines. Expression of CCT8 was correlated directly with the histologic grades and tumor size of HCC and high expression of CCT8 was associated with a poor prognosis. CCT8 depletion by siRNA inhibited cell proliferation and blocked S-phase entry in HuH7 cells. These results suggested that CCT8 might be an oncogene and participate in HCC cell proliferation. These findings provide a potential therapeutic strategy for the treatment of HCC.
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Nucleophilic trapping nitrilimine generated by photolysis of diaryltetrazole in aqueous phase.
Molecules
PUBLISHED: 10-01-2013
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Nitrilimine generated by photolysis of diaryltetrazole in aqueous phase under mild conditions was trapped by nucleophiles including amines and thioalcohols. The representative products were characterized, while products with all 20 natural amino acids and a peptide were observed by MALDI-TOF mass spectroscopy. Competitive studies showed that this reaction also occurred in the presence of acrylamide. These results provided new information for understanding the potential side reactions when tetrazole-alkene pairs were used as a bioorthogonal reaction in labeling proteins and related studies in buffered systems.
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Fatty acid ethyl esters production in aqueous phase by the oleaginous yeast Rhodosporidium toruloides.
Bioresour. Technol.
PUBLISHED: 07-30-2013
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Fatty acid ethyl esters (FAEEs) are attractive biofuel molecules. Conventional FAEEs production process uses triglycerides and ethanol as feedstocks and is sensitive to water contents. In this work, we show that the oleaginous yeast Rhodosporidium toruloides cells are capable of converting lipids into FAEEs intracellularly in aqueous phase. Up to 73% of cellular neutral glycerides could be converted into FAEEs when lipid-rich cells were incubated for 84h at 35°C, pH 6.0 in a broth containing 10 vol% ethanol. It was found that neutral glycerides were first hydrolyzed to free fatty acids followed by esterification and that lipid droplets played important roles in the process. This new process provides a novel opportunity for integration of microbial lipid production technology with bioethanol fermentation for more efficient production of drop-in biofuels from renewable resources.
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The relationship between Cyclin G1 and survival in patients treated surgically for HCC.
Hepatogastroenterology
PUBLISHED: 07-24-2013
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Cyclin G1 is a cell-cycle-regulatory protein that is frequently seen in elevated amounts in malignant tissue, including astrocytomas; melanoma; carcinoma of the esophagus, lung, and breast; as well as cancer of the cervix, uterus, and ovary. By contrast, it has demonstrated inhibitory activity in human hepatocellular carcinoma (HCC).
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Synergistic effect of EMS1-shRNA and sorafenib on proliferation, migration, invasion and endocytosis of SMMC-7721.
J. Mol. Histol.
PUBLISHED: 07-13-2013
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To investigate the synergistic effect of EMS1-PSilencer4.1-shRNA (EMS1-shRNA) and sorafenib on biological behaviors of HCC cell line SMMC-7721. EMS1-shRNA was constructed and transfected into SMMC-7721 cells. Decreased levels of EMS1/cortactin were tested in RT-QPCR and Western blot assay. Proliferation, migration, invasion, and endocytosis of SMMC-7721 were tested through CCK8 assay, scratch test, transwell invasion assay and transferrin endocytosis assay, respectively. Raf-1 was detected by Western blot assay. HCC xenograft model was prepared to observe tumor growth. Animals were euthanized and their subcutaneous lesions were weighed. Then the tissues were fixed and paraffin sections were prepared. Cortactin and PCNA (a proliferation marker) were then detected by immunohistochemistry. As compared with untreated group, the levels of EMS1 gene and cortactin protein in EMS1-shRNA-transfected group were significantly reduced; Among EMS1-shRNA-transfected group, sorafenib-treated group and combined group, the levels of proliferation at 48 h were reduced to 83.69, 57.18, 41.94 %; the levels of migration were reduced to 49.69, 60.83, and 21. 67 %; the levels of invasion were reduced to 42.97, 53.65, 18.18 %; the levels of endocytosis were reduced to 37.15, 97.95 % (p > 0.05), 20.68 % (p < 0.05, respectively). Western blot assay showed levels of Raf-1 were reduced to 68.56, 59.09, 21.90 %. The tumor volume and weight of nude mice HCC xenograft tumors were reduced significantly either (p < 0.05, respectively). Immunohistochemistry showed levels of cortactin and PCNA were reduced to 35.69, 93.84, 23.68 and 87.69, 43.84, 33.68 % in each group, respectively. The biological behaviors of SMMC-7721 were inhibited in the presence of EMS1-shRNA and sorafenib both alone and in combination. The combination of the agents improved the curative effect over either single agent, showing synergetic effect.
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Switchable domain partitioning and diffusion of DNA origami rods on membranes.
Faraday Discuss.
PUBLISHED: 06-29-2013
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Recently, DNA origami became a powerful tool for custom-shaped functional biomolecules. In this paper, we present the first approach towards assembling amphipathic three-dimensional DNA origami nanostructures and assessing their dynamics on the surface of freestanding phospholipid membranes. Our nanostructures were stiff DNA origami rods comprising six DNA helices. They were functionalized with hydrophobic cholesteryl-ethylene glycol anchors and fluorescently labeled at defined positions. Having these tools in hand, we could demonstrate not only the capability of the amphipathic nanorods to coat membranes of various phospholipid compositions, but also their switchable liquid-ordered/liquid-disordered partitioning on phase separated membranes. The observed translocation of our nanostructures between different domains was controlled by divalent ions. Moreover, selective fluorescent labeling enabled us to distinguish between the translational and rotational diffusion of our six helix bundles on the membranes by fluorescence correlation spectroscopy. The obtained data reveal how DNA origami can be employed as a valuable tool in membrane biophysics.
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Chaperone-like effects of a scFv antibody on the folding of human muscle creatine kinase.
Protein Eng. Des. Sel.
PUBLISHED: 06-23-2013
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Molecular chaperones play an essential role in assisting the folding of a myriad of nascent peptides to form different biologically active proteins. Therefore, their low substrate specificity is important for the functions of these housekeeping proteins. However, discovering chaperones which assist the folding of a particular protein can shed new light on the folding pathway of the protein, offering an interesting approach for developing specific therapeutic agents to treat protein-misfolding diseases. Screening of antibodies with chaperone-like function represents a novel strategy to meet the challenges. In this study, some single-chain variable fragment (scFv) antibodies were selected from a high-capacity phage antibody library using human muscle creatine kinase (HCK) as antigen. A scFv antibody (scFv A4) was determined to inhibit aggregation and favor recovery of the native conformation of HCK during its refolding. This antibody also increased the stability of HCK during its heat-induced unfolding process. Our findings demonstrate that scFv A4 has dual-chaperone-like activities: assisting in correct protein folding as well as protecting the native protein from unfolding. A molecular mechanism by which scFv A4 exhibits chaperone-like effects on HCK was proposed. This study demonstrates that phage antibody libraries can lead to chaperone-like proteins, and the specificity of the resulting antibody toward its antigen could provide new molecular details regarding how the chaperone interacts with the proteins unfolding and folding pathways.
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Upregulated expression of CAP1 is associated with tumor migration and metastasis in hepatocellular carcinoma.
Pathol. Res. Pract.
PUBLISHED: 06-19-2013
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Hepatocellular carcinoma (HCC) is one of the most common cancers that exhibits high incidences of intrahepatic metastasis and tumor recurrence. Adenylate cyclase-associated protein 1 (CAP1), a protein involved in the regulation of actin filaments, was recently reported to play a role in cell motility and the pathology of pancreatic cancer. In this study, we examined a potential role of CAP1 in HCC progression, and found that CAP1 was overexpressed in HCC specimens compared with adjacent noncancerous liver tissues by Western blot analysis and real-time PCR assay. Further, immunohistochemical analysis in 107 HCC specimens revealed that overexpression of CAP1 was closely correlated only with tumor metastasis, but not with other clinicopathologic parameters. Univariate and multivariate survival analyses showed that CAP1 could be an independent prognostic factor for patients survival. In addition, immunofluorescent assay demonstrated that CAP1 was colocalized with actin in the leading edge of lamellipodium in HCC cells. Importantly, knocking-down the expression of CAP1 using small interfering RNA (siRNA) targeting CAP1 led to impaired migration of HCC cells. Collectively, our results indicated that upregulated expression of CAP1 might contribute heavily to the metastasis of HCC.
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Statistical behavior analysis and precision optimization for the laser stripe center detector based on Stegers algorithm.
Opt Express
PUBLISHED: 06-06-2013
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Triangulation laser range scanning, which has been wildly used in various applications, can reconstruct the 3D geometric of the object with high precision by processing the image of laser stripe. The unbiased line extractor proposed by Steger is one of the most commonly used algorithms in laser stripe center extraction for its precision and robustness. Therefore, it is of great significance to assess the statistical performance of the Steger method when it is applied on laser stripe with Gaussian intensity profile. In this paper, a statistical behavior analysis for the laser stripe center extractor based on Steger method has been carried out. Relationships between center extraction precision, image quality and stripe characteristics have been examined analytically. Optimal scale of Gaussian smoothing kernel can be determined for each laser stripe image to achieve the highest precision according to the derived formula. Flexible three-step noise estimation procedure has been proposed to evaluate the center extraction precision of a typical triangulation laser scanning system by simply referring to the acquired images. The validity of our analysis has been verified by experiments on both artificial and natural images.
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Decreased expression of SERPINB1 correlates with tumor invasion and poor prognosis in hepatocellular carcinoma.
J. Mol. Histol.
PUBLISHED: 05-29-2013
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SERPINB1 (serine protease inhibitor, clade B, member1) is a member of the SERPINB family. Recent studies suggested that SERPINB1 may suppress the migration and invasion of lung and breast cancers. In this study, we investigated a possible involvement of SERPINB1 in the regulation of hepatocellular carcinoma metastasis (HCC). The expression of SERPINB1 was evaluated using western blot analysis in 8 paired fresh HCC specimens and immunohistochemistrical assay on 67 paraffin-embedded HCC slices. SERPINB1 was downregulated in HCC specimens and correlatively related with two clinicopathologic features of HCC, metastasis (P = 0.000) and vein invasion (P = 0.006). Univariate and multivariate survival analyses showed a lower level of SERPINB1 expression is associated with poor prognosis and clinical outcome (P = 0.001). In addition, small interfering RNA targeting SERPINB1 was used to knock down the expression of SERPINB1 in Huh7 and BEL-7404 cells. We showed that interference of SERPINB1 promoted migration and invasion of HCC cells, while cell proliferation was not affected. Finally, we observed an apparent increase in the level of active matrix metalloproteinase-2 (MMP2) after SERPINB1 knockdown, implying that SERPINB1 might participate in the regulation of HCC metastasis through modulating the activation of matrix metalloproteinases. Overall, our results suggested an inhibitory role of SERPINB1 in the migration and invasion of HCC, implying that SERPINB1 might be a potential prognostic indicator of HCC metastasis.
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Suppression of KIF3B Expression Inhibits Human Hepatocellular Carcinoma Proliferation.
Dig. Dis. Sci.
PUBLISHED: 05-21-2013
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Human hepatocellular carcinoma (HCC) is one of the most common fatal cancers and an important health problem worldwide, but its mechanism is still unclear. Microtubule (MT) kinesin motor proteins orchestrate a variety of cellular processes (e.g. mitosis, motility and organelle transportation) and have been involved in human carcinogenesis. KIF3B, the kinesin superfamily of proteins (KIFs), plays an important role in the regulation of mitotic progression.
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[Meta analysis of acupuncture in the treatment of optic atrophy].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 04-03-2013
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To evaluate the efficacy and safety of acupuncture for optic atrophy.
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Design, synthesis, and pharmacological characterization of novel endomorphin-1 analogues as extremely potent ?-opioid agonists.
J. Med. Chem.
PUBLISHED: 03-28-2013
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Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural ?-methylene-?-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-?Pro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the ?-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-?Pro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki(?) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, Emax = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.
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Protein arginine allylation and subsequent fluorophore targeting.
Chembiochem
PUBLISHED: 03-25-2013
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Protein allylation and fluorophore targeting: Arginine residues of the yeast nuclear ribonucleoprotein Npl3 were extensively modified by Hmt1-catalyzed allylation reaction with allyl-SAM as the allyl group donor. The allylated protein was further treated with tetrazole compounds under UV irradiation, leading to formation of protein-attached fluorescent products.
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Glyoxylate reductase/hydroxypyruvate reductase: a novel prognostic marker for hepatocellular carcinoma patients after curative resection.
Pathobiology
PUBLISHED: 03-07-2013
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Glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a key enzyme in the glyoxylate cycle. Its deficiency causes primary hyperoxaluria type 2. We first noticed that GRHPR was also lost in human hepatocellular carcinoma (HCC) and proliferative HCC cells. The aim of the present study was to investigate the potential clinical utility of GRHPR in HCC.
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Gaussian pulse gated InGaAs/InP avalanche photodiode for single photon detection.
Opt Lett
PUBLISHED: 03-05-2013
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The capacitive response noise has been problematic for high-speed single photon detection based on gated InGaAs/InP avalanche photodiodes. Traditionally, the noise must be suppressed by complex electronic circuit if low afterpulse probability is desired. In this Letter, we propose a compact and flexible method for noise cancellation, which gates the photodiode with a Gaussian pulse. Because of the differential effect of junction capacitor, the shape of the capacitive response output in our method is the first-order derivative of the Gaussian function that can be matched by the rising edge of a delayed and attenuated version of the gating pulse itself. With matching signal, the avalanche pulse is raised onto a flat platform that can be easily discriminated from the background. For 1550 nm optical signal, the detection efficiency could reach 10.2% with 9.7×10(-6) per gate dark count probability and 3.4% afterpulse probability at 80 MHz gating frequency. Experimental results have shown that the proposed method can decrease the afterpulse probability sharply while maintaining the detection efficiency and dark count performance.
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The prognostic significance of FOXQ1 oncogene overexpression in human hepatocellular carcinoma.
Pathol. Res. Pract.
PUBLISHED: 03-04-2013
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FOXQ1 (forkhead box Q1) is a forkhead transcription factor, and FOX genes play significant roles in a series of biological processes. The aim of our study was to verify the importance of FOXQ1 as a prognostic indicator in HCC patients. One-step quantitative real-time PCR was performed to identify the expression of FOXQ1 mRNA in HCC and corresponding non-cancerous tissues. FOXQ1 expression was then evaluated by immunohistochemistry (IHC) using tissue microarray. Finally, we analyzed FOXQ1 expression and clinicopathological factors in 114 HCC patients using SPSS 20.0 software. FOXQ1 expression at the transcriptional level in HCC cells was much higher than in the noncancerous cells (P=0.012, respectively). Comparison of clinicopathological characteristics and FOXQ1 expression in HCC by IHC and ?(2) tests showed that high FOXQ1 expression was linked to large tumor diameter, high serum ?-fetoprotein levels and later stage grouping with tumor node metastasis classification. Kaplan-Meier and Cox regression analyses showed that high FOXQ1 expression and regional lymph node metastasis were independent prognostic factors. Our study demonstrates that an aggressive malignant phenotype of HCC is strongly linked to high FOXQ1 expression, and FOXQ1 may be a novel target in HCC therapy. Furthermore, it is likely that FOXQ1 is an oncogene in HCC.
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Minimal peptide motif for non-covalent peptide-heparin hydrogels.
J. Am. Chem. Soc.
PUBLISHED: 02-12-2013
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Reduction of complexity of the extracellular matrix (ECM) to a non-covalent structure with minimal chemically defined components represents an attractive avenue for understanding the biology of the ECM. The resulting system could lead to the design of tailor-made biomaterials that incorporate varying functionalities. Negatively charged glycosaminoglycans are the major components of the ECM. Their interaction with positively charged proteins is important for dynamic three-dimensional scaffold formation and function. We designed and screened minimal peptide motifs whose conjugates with polyethylene glycol interact with heparin to form non-covalent hydrogels. Here we show the structure/function relationship of the (RA)(n) and (KA)(n) motifs and determined that both basic residues and the heparin-induced ?-helix formation are important for the assembly process. Simple rules allowed us to tune various aspects of the matrix system such as the gelation rates, biodegradability, rheological properties, and biofunctionality. The hydrogels can encapsulate cells and support cell survival.
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Increased ?-tubulin1b expression indicates poor prognosis and resistance to chemotherapy in hepatocellular carcinoma.
Dig. Dis. Sci.
PUBLISHED: 02-05-2013
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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. It is important to understand molecular mechanisms of HCC progression and to develop clinically useful biomarkers for the disease.
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Indications, outcomes, and complications of pedicled propeller perforator flaps for upper body defects: a systematic review.
Arch Plast Surg
PUBLISHED: 01-14-2013
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The aim of this investigation was to systematically review the current literature to provide the best data for indications, outcomes, survival, and complication rates of pedicled propeller perforator flaps for upper body defects.
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Potentially functional genetic variants in microRNA processing genes and risk of HBV-related hepatocellular carcinoma.
Mol. Carcinog.
PUBLISHED: 01-07-2013
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Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC.
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Anticancer effects of a novel class rosin-derivatives with different mechanisms.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-06-2013
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In this Letter, the anticancer activity of novel rosin-derivatives introducing indicated side chains at position C18 of dehydroabietic acid (DHAA) was reported. Gratifyingly, all of these derivatives showed significantly cytotoxicity toward diverse human carcinoma cell lines. We found the compound 4 could induce cell membrane damage at high concentration as well as cell apoptosis at low concentration. However, compound 5, attachment of quinidine to dehydroabietic acid via thiourea bond, only induced apoptotic cell death. In addition, all these active compounds induced apoptosis mainly through mitochondrial-dependent pathway. Interestingly, compound 5 exhibited the highest anticancer activity and little toxicity to normal cells compared with the other derivatives. Therefore, 5 merits further investigation as a potential agent for future anticancer treatment.
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Perioperative allogenenic blood transfusion is associated with worse clinical outcomes for hepatocellular carcinoma: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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The impact of perioperative allogenenic blood transfusion (ABT) on clinical outcomes for hepatocellular carcinoma (HCC) is conflicting and unclear. The aim of this meta-analysis is to evaluate the association between ABT and HCC clinical outcomes. Outcomes evaluated were all-cause death, tumor recurrence and postoperative complications.
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Preparation of ethosomes and deformable liposomes encapsulated with 5-fluorouracil and their investigation of permeability and retention in hypertrophic scar.
J Nanosci Nanotechnol
PUBLISHED: 11-22-2011
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With the aim of comparing scar penetration efficiency and retention between ethosomes and deformable liposomes both encapsulated with 5-fluorouracil (5-FU), the 5-FU ethosomal suspensions (5-FU ES, 81.74 +/- 9.37 nm) and the 5-FU Deformable Liposomal Suspensions (5-FU DS, 73.7 +/- 9.45 nm) were prepared respectively by Touitou method and Cevc method, their sizes were determined by Particle Sizer System (PSS), and their entrapment Efficiency (EE) was detected by ultracentrifugation and microcolumn centrifugation. Their transdermal delivery experiments were done in hypertrophic scars in vitro. The permeated amount of 5-FU and retention contents of 5-FU were both calculated by High Performance Liquid Chromatography (HPLC). Fluorescence intensities of ES and DS labeled with Rodanmin 6GO (Rho) were measured by Laser Scanning Microscopy (LSM). The control groups such as the 5-FU and empty ethosomal vesicles (5-FU + EEV), the 5-FU and empty deformable liposomal vesicles (5-FU + EDV) and 5-FU PBS Solution (5-FU Sol) were set up. Results showed that, prepared 5-FU ES was 81.74 +/- 9.37 nm in size, 5-FU DS was 73.7 +/- 9.45 nm, EE of 5-FU ES was 10.95%, EE of 5-FU DS was 15.05%. Within 24 hours, in the group of 5-FU ES, the penetration amount of 5-FU in scar was 14.12 +/- 0.1 microg/mL/cm2, the retention contents of 5-FU was 10.74 +/- 1.17 microg/cm2, and the fluorescence intensity of Rho in hypertrophic scar tissues were 182 +/- 18.3; in the group of 5-FU DS: the penetration amount of 5-FU was 12.35 +/- 1.21 microg/mLcm2; the retention contents of 5-FU was 17.48 +/- 0.82 microg/cm2, and the fluorescence intensity of Rho was 241.45 +/- 7.63; there existed statistical difference between penetration amount in the group of 5-FU ES and that in the group of 5-FU DS as well as control groups (P < 0.05, P < 0.01), the penetration amount in the group of ES is markedly higher than DS group or control groups. Conversely, the retention contents of 5-FU and the fluorescence intensity of Rho in DS group were higher than those in ES group and control groups (P < 0.05, P < 0.01). In conclusion, both ES and DS could deliver 5-FU into the hypertrophic scars effectively. ES has better permeability of 5-FU than DS, DS has higher entrapment efficiency of 5-FU, and more 5-FU deposition in hypertrophic scar than ES. We should select ES or DS encapsulated with 5-FU according to clinical demand for hypertrophic scar therapy.
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Combination of thiazolidinedione and hydralazine suppresses proliferation and induces apoptosis by PPAR? up-expression in MDA-MB-231 cells.
Exp. Mol. Pathol.
PUBLISHED: 08-09-2011
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No proven targeted therapy is currently available for the treatment of triple-negative breast cancer (TNBC). Ligand activation of peroxisome-activated receptor (PPAR)? induces antitumor effects in cancer but not obviously in TNBC. In TNBC cells, combined treatment with thiazolidinedione and demethylation drugs Hydralazine up-regulated protein and mRNA levels of PPAR?. Besides, the combination of two drugs promote antiproliferative and apoptotic effects in TNBC cells and decrease the proliferation index in the tumor xenografts. Taken together, our results suggest that multidrug regimens including a combination of Thiazolidinedione and Hydralazine may provide a therapeutic advantage in TNBC.
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Clinical experience of the treatment of giant congenital benign tumours of the back.
J Plast Surg Hand Surg
PUBLISHED: 07-20-2011
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Congenital giant benign tumours of the back are rarely seen or reported. They pose two challenges to plastic surgeons: copious intraoperative bleeding, and an extensive raw area left after removal of the tumour. We have treated five cases of congenital giant benign tumour of the back. The largest was a neurofibroma in a woman, which weighed 36.29 kg and she had 10,000 ml of blood transfused to replace the blood loss during operation. We achieved total excision of the tumours in all cases and covered the extensive wounds with skin harvested from the tumours themselves in one stage. Among the five cases, four were neurofibromas and one was a giant naevus. All grafted skin took, and there were no recurrences. The tumours were radically excised in one stage and the extensive wounds covered with the skin with good take and no risk of recurrence.
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[Progress in biofixation of CO2 from combustion flue gas by microalgae].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 06-10-2011
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Global warming caused by the increasing CO2 concentration in atmosphere is a serious problem in the international political, economic, scientific and environmental fields in recent years. Intensive carbon dioxide capture and storage (CCS) technologies have been developed for a feasible system to remove CO2 from industrial exhaust gases especially for combustion flue gas. In these technologies, the biofixation of CO2 by microalgae has the potential to diminish CO2 and produce the biomass. In this review, the current status focusing on biofixation of CO2 from combustion flue gases by microalgae including the selection of microalgal species and effect of flue gas conditions, the development of high efficient photobioreactor and the application of microalgae and its biomass product were reviewed and summarized. Finally, the perspectives of the technology were also discussed.
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Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis.
Int. J. Cancer
PUBLISHED: 04-28-2011
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The detection of nonsmall cell lung cancer (NSCLC) at an early stage presents a daunting challenge due to the lack of a specific noninvasive marker. The discovery of microRNAs (miRNAs), particularly those found in serum, has opened a new avenue for tumor diagnosis. To determine whether the expression profile of serum miRNAs can serve as a NSCLC fingerprint, we performed Taqman probe-based quantitative RT-PCR assay to selected differentially expressed serum miRNAs from a sample set including 400 NSCLC cases and 220 controls, and risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. After a two-phase selection and validation process, 10 miRNAs were found to have significantly different expression levels in NSCLC serum samples compared with the control serum samples. Risk score analysis showed that this panel of miRNAs was able to distinguish NSCLC cases from controls with high sensitivity and specificity. Under ROC curves, the AUC for tumor identification in training set and validation set were 0.966 and 0.972, respectively. Furthermore, the expression profile of the 10-serum miRNAs was correlated with the stage of NSCLC patients, especially in younger patients and patients with current smoking habits. More importantly, the serum miRNA-based biomarker for early NSCLC detection was supported by a retrospective analysis in which the 10-serum miRNA profile could accurately classify serum samples collected up to 33 months ahead of the clinical NSCLC diagnosis. Taken together, we demonstrate that the profiling of 10-serum miRNAs provides a novel noninvasive biomarker for NSCLC diagnosis.
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In vitro study of ethosome penetration in human skin and hypertrophic scar tissue.
Nanomedicine
PUBLISHED: 03-11-2011
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The purpose of this study is to characterize a novel transdermal delivery carrier, ethosomes containing 5-fluorouracil. The delivery of drugs from ethosomes in human hypertrophic scar (HS) and the mechanisms of action of ethosomes in human HS were investigated. Percutaneous ethosome permeation was evaluated in vitro in human HS and skin using a Franzs cell. The amount of 5-fluorouracil that permeated HS and skin after 24 hours was most abundant in ethosomes via HS (E-Scar), followed by hydroethanolic solution via HS (H-Scar), ethosomes via skin (E-Skin), and hydroethanolic solution via skin (H-Skin). The penetration of ethosomes in HS and skin was analyzed by ethosomes fluorescently labeled with rhodamine 6GO using confocal laser scanning microscopy. The fluorescence intensity after application for 24 hours was highest in E-Scar, followed by E-Skin, H-Scar, and H-Skin, which indicates the penetration of ethosomes in HS was greatest. In conclusion, we consider that ethosomes are a highly efficient carrier in HS.
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Double-stranded RNA-induced TLR3 activation inhibits angiogenesis and triggers apoptosis of human hepatocellular carcinoma cells.
Oncol. Rep.
PUBLISHED: 02-10-2011
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Toll-like receptor 3 (TLR3) is a member of the Toll-like receptors which recognize pathogen-associated molecular patterns leading to the activation of the innate immune response. Recent reports have strongly indicated that they play important roles in cancer cells. Since TLR3 has been recently suggested as a possible therapeutic target in certain types of cancers, in the present study, TLR3 expression and its function were explored in hepatocellular carcinoma (HCC) and human umbilical vein endothelial cells (HUVECs). The expression of TLR3 in various HCC cell lines and HUVECs was detected using quantitative real-time PCR (qRT-PCR) and immunocytochemistry. TLR3 activity was determined by Luciferase reporter assays. The effects of TLR3 double-stranded RNA (dsRNA) agonists on angiogenesis were tested by aortic ring assay and HUVEC tube formation experiments. After dsRNA treatment, cell apoptosis was assessed by Annexin V and PI staining through FACS, and the migration ability was measured by a migration assay. The results showed that TLR3 was expressed in HCC cell lines and HUVECs at the mRNA and protein level. Luciferase reporter assays demonstrated that TLR3 was activated by the dsRNA analog BM-06 or poly(I:C). Rat aortic ring outgrowth and endothelial cell tube formation were suppressed after treatment with dsRNA. In addition, dsRNA triggered apoptosis in MHCC97H, SMMC-7721 and HUVEC cell lines and inhibited cell migration. In conclusion, TLR3 agonists not only affect tumor microenvironment by suppressing angiogenesis but also directly induce tumor cell apoptosis and inhibit tumor cell migration. TLR3 may be a new target for HCC therapy.
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Preparation and characterization of different sizes of ethosomes encapsulated with 5-fluorouracil and its experimental study of permeability in hypertrophic scar.
J Nanosci Nanotechnol
PUBLISHED: 12-07-2010
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With the aim of investigating scar penetration efficiency of different sizes of ethosomes encapsulated with Fluorouracil, three kinds of ethosomes with different sizes were prepared by extruding the vesicles through polycarbonate membrane filters, their encapsulation efficiency of Fluorouracil (5-FU) were investigated by dialysis method, their scar-penetration efficiencies were analyzed by filling Rodanmin 6GO into ethosomes and using confocal laser scanning microscopy (CLSM). The prepared ethosomes were 216 +/- 19 nm, 107 +/- 13 nm, and 65 +/- 10 nm in diameter respectively, and exhibited good dispersibility. Their encapsulation efficiency of 5-FU were 12%, 34%, and 41%, respectively. The results indicated that the 5-FU penetration was reversely related to the size of the size of the ethosomes. The ethosomes of 65 nm in diameter exhibited maximal fluorescence penetration efficiency which could reach the deep layer of dermis of hypertrophic scar. In conclusion, three different sizes of 5-FU ethosomes were prepared successfully, the ethosomes of 65 nm in diameter with 5-FU can penetrate scar high efficiently, which has potential in application such as anti-scar drug carriers in scar therapy in near future.
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Reversible photoswitching of protein function.
Mol Biosyst
PUBLISHED: 08-09-2010
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Using light to tune the activity of proteins represents a very attractive avenue for creating various temporal interferences in living systems. In this mini-review, we highlight a few recent developments in this broad and exciting field. Among the various methods, we have discussed in more detail the advantages and future challenges in using light switchable drugs to regulate the signaling proteins in the immune system.
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A model of sequential heart and composite tissue allotransplant in rats.
Plast. Reconstr. Surg.
PUBLISHED: 07-03-2010
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Some of the 600,000 patients with solid organ allotransplants need reconstruction with a composite tissue allotransplant, such as the hand, abdominal wall, or face. The aim of this study was to develop a rat model for assessing the effects of a secondary composite tissue allotransplant on a primary heart allotransplant.
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A technique to perfuse cadavers that extends the useful life of fresh tissues: the Duke experience.
Anat Sci Educ
PUBLISHED: 06-30-2010
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The demand for laboratory-based teaching and training is increasing worldwide as medical training and education confront the pressures of shorter training time and rising costs. This article presents a cost-effective perfusion technique that extends the useful life of fresh tissue. Refrigerated cadavers are preserved in their natural state for up to 45 days with a daily working period of ten hours. Tissues maintain their color and natural consistency throughout this period. This new process for preservation of tissue opens the door to improved surgical training and to numerous research opportunities.
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IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population.
Int. J. Cancer
PUBLISHED: 03-30-2010
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To investigate the association between the potentially functional polymorphisms in IL12A and IL12B, HBV infection and risk of hepatocellular carcinoma in a Chinese population, we genotyped three polymorphisms, rs568408 (3UTR G>A), rs2243115 (5UTR T>G) in IL12A and rs3212227 (3UTR A>C) in IL12B in a case-control study of 869 hepatocellular carcinoma (HCC) cases and 891 cancer-free controls. We found that the IL12A rs568408 GA/AA variant genotypes were associated with a significantly increased risk of HCC (adjusted odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.17-2.00), compared with the wild-type GG homozygote. In the stratified analyses, the increased risk of HCC associated with rs568408 GA/AA was more evident in patients who were negative for HBsAg (adjusted OR = 1.71, 95% CI = 1.23-2.39). However, no significant associations between IL12A rs2243115 T/G, IL12B rs3212227 A/C and risk of HCC were observed. Our findings indicate that IL12A rs568408 may contribute to the risk of HCC and modify HCC risk associated with HBV infection.
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Isolation of a small-molecule inhibitor of the antiapoptotic protein Bcl-xL from a DNA-encoded chemical library.
ChemMedChem
PUBLISHED: 03-16-2010
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Bcl-xL is an antiapoptotic member of the Bcl-2 protein family and an attractive target for the development of anticancer agents. Here we describe the isolation of binders to Bcl-xL from a DNA-encoded chemical library using affinity-capture selections and massively parallel high-throughput sequencing of >30,000 sequence tags of library members. The most potent binder identified, compound 19/93 [(R)-3-(amido indomethacin)-4-(naphthalen-1-yl)butanoic acid], bound to Bcl-xL with a dissociation constant (K(d)) of 930 nM and was able to compete with a Bak-derived BH3 peptide, an antagonist of Bcl-xL function.
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CTLA-4 gene polymorphism +49 A/G contributes to genetic susceptibility to two infection-related cancers-hepatocellular carcinoma and cervical cancer.
Hum. Immunol.
PUBLISHED: 03-07-2010
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Accumulated evidence suggested that cytotoxic T-lymphocyte antigen 4 (CTLA4) plays an important role in the negative regulation of T-cell proliferation and activation, and thus participates in antitumor immunity and cancer surveillance. Previously we reported that the CTLA4 49A/G (rs231775) single nucleotide polymorphism (SNP) was a candidate cancer susceptibility marker for breast, lung, esophageal, and gastric cancers. In the present study, we expanded our study to two infection-related cancers, namely, hepatocellular carcinoma (HCC) and cervical cancer. We genotyped rs231775 in two independent case-control studies of 864 HCC patients and 864 control subjects, and 719 cervical cancer patients and 719 control subjects. In the multivariate logistic regression models, CTLA4 +49 A/G variant genotype was associated with increased risk (AA vs GG) by 1.43-fold (95% CI = 0.94-2.17) for HCC, and 1.66-fold (95% CI = 1.13-2.44) for cervical cancer. Taken together, the results suggest that CTLA4 rs231775 may serve as a common cancer susceptibility marker.
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A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma.
Int. J. Cancer
PUBLISHED: 01-21-2010
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The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located in the CpG island and might affect transcription factor GATA binding and therefore pri-miR-34b/c expression. In our study, we hypothesized that SNPs miR-34b/c rs4938723 and TP53 Arg72Pro may independently or jointly contribute to primary hepatocellular carcinoma (HCC) susceptibility. We then genotyped the 2 SNPs in a case-control study of 501 patients with primary HCC and 548 cancer-free controls in a Chinese population. We observed that the variant genotypes of miR-34b/c rs4938723 were associated with significantly increased HCC risks compared with the wild-type TT genotype (adjusted OR = 1.37, 95% CI =1.06-1.78 for TC; OR = 1.53, 95% CI = 1.02-2.31 for CC and OR = 1.40, 95% CI = 1.10-1.80 for TC/CC). Furthermore, we found a significant interaction between alcohol drinking and SNP rs4938723 on HCC risk (p = 0.05 for multiplicative and p = 0.01 for additive interaction). However, we did not find any main effect of TP53 Arg72Pro on HCC risk in this population. These findings indicate that the potentially functional SNP rs4938723 in the promoter region of pri-miR-34b/c may contribute to the susceptibility of HCC in this Chinese population.
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An innovative reactor-type biosensor for BOD rapid measurement.
Biosens Bioelectron
PUBLISHED: 11-19-2009
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Biochemical oxygen demand (BOD) is one of the most important and widely used parameters for characterizing the organic pollution of water and wastewater. In this paper, a novel reactor-type biosensor for rapid measurement of BOD was developed, based on using immobilized microbial cell (IMC) beads as recognition bio-element in a completely mixed reactor which was used as determining chamber, replacing the traditionally used membrane as recognition bio-element. The IMC beads were freely suspended in the aqueous solution, so the mass transfer resistance for dissolved oxygen and organic compounds significantly reduced, and the quantity of the microbial cells used as recognition element can be easily adjusted, in comparison with the traditional membrane-type BOD biosensor, in which exists a unadjustable contradiction between the quantity of biomass and the thickness of the bio-membrane, thus limiting the stability and the detection limit. This novel kind of BOD biosensor significantly increased the sensitivity of the response, the detecting precision and prolonged the life time of the recognition element. The experimental data showed that the most appropriate temperature for biochemical reaction in the reactor was 30 degrees C, and the IMC beads could keep the bioactivity for about 70d at the detecting frequency of 8 times every day. The standard deviation of repeatability and the reproducibility of responses were within +/-6.4% and +/-5.0%, respectively, which are within acceptable bias limits, and meet the requirement of BOD rapid measurement.
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[Optimization of cloning and expression of beta-glucanase gene from Bacillus amyloliquefaciens].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 07-30-2009
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To compare of performance of beta-1,3-1,4-glucanase gene (bgl) in different expression systems, the beta-1,3-1,4-glucanase gene (GenBank Accession No. EU623974) was amplified from Bacillus amyloliquefaciens BS5582 by PCR and was cloned into three vectors pEGX-4T-1, pET20b(+) and pET28a(+) to construct pEGX-4T-1-bgl, pET20b(+)-bgl and pET28a(+)-bgl recombinant plasmids. The pEGX-4T-1-bgl was transformed into three different Escherichia coli host strains. The pET20b (+)-bgl and pET28a (+)-bgl were transformed into E. coli BL21 (DE3) respectively. Recombinant beta-glucanase was expressed by IPTG inducement in these recombinants. E. coli BL21 (DE3)-pET28a (+)-bgl had the highest enzyme activity. In Luria-Bertani medium, the total enzyme activity was (322.0 +/- 8.8) U/mL, which was 40.1% of original strain in optimal shaking flask condition. This recombinants performance was studied in Terrific Broth medium under inducement of IPTG and lactose at the same time., and the highest total enzyme activity could reach (1883.3 +/- 45.8) U/mL (818.8% of the original), which indicate that the recombinant strain has a good value in industry application.
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Augmented photoswitching modulates immune signaling.
Nat. Chem. Biol.
PUBLISHED: 05-12-2009
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Reversible and non-invasive photoswitching of the immunosuppressive effect of a drug would be a very valuable tool for precisely regulating the immune system. Using a combination of protein borrowing and two-photon photoisomerization, we designed and synthesized derivatives of cyclosporin A. Here we demonstrate photoswitching of the local conformation within small molecules, which we used to modulate inhibitory potencies for cyclophilin, influence ternary and quaternary complex formations and regulate T-cell transcriptional activation in situ.
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Discovery of TNF inhibitors from a DNA-encoded chemical library based on diels-alder cycloaddition.
Chem. Biol.
PUBLISHED: 04-07-2009
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DNA-encoded chemical libraries are promising tools for the discovery of ligands toward protein targets of pharmaceutical relevance. DNA-encoded small molecules can be enriched in affinity-based selections and their unique DNA "barcode" allows the amplification and identification by high-throughput sequencing. We describe selection experiments using a DNA-encoded 4000-compound library generated by Diels-Alder cycloadditions. High-throughput sequencing enabled the identification and relative quantification of library members before and after selection. Sequence enrichment profiles corresponding to the "bar-coded" library members were validated by affinity measurements of single compounds. We were able to affinity mature trypsin inhibitors and identify a series of albumin binders for the conjugation of pharmaceuticals. Furthermore, we discovered a ligand for the antiapoptotic Bcl-xL protein and a class of tumor necrosis factor (TNF) binders that completely inhibited TNF-mediated killing of L-M fibroblasts in vitro.
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NIR-responsive silica-coated NaYbF(4):Er/Tm/Ho upconversion fluorescent nanoparticles with tunable emission colors and their applications in immunolabeling and fluorescent imaging of cancer cells.
J Phys Chem C Nanomater Interfaces
PUBLISHED: 03-02-2009
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NaYbF(4): RE upconversion (UC) fluorescent nanoparticles (NPs) were synthesized with variable rare-earth dopants (RE= Er(3+), Tm(3+), or Ho(3+), or a combination of these ions), from rare-earth stearate precursors in a water-ethanol-oleic acid system by using a two-phase solvothermal method. The NPs were shown to emit visible light such as orange, yellow, green, cyan, blue or pink light in response to near infrared (NIR) irradiation, and their emission colors could be simply tuned by changing either the co-dopant concentration or dopant species. The UC NPs were well-dispersed and spherical with an average size of 15~35 nm. They emitted strong UC fluorescence under the 980 nm NIR excitation. The effects of solvothermal reaction time and temperature on nanoparticle size and phase structure as well as UC fluorescence intensity were systematically studied. Water dispersibility was achieved by forming a silica coat on the surface of the UC NPs. After animo-functionalization, the silica-coated UC NPs were chemically conjugated with the rabbit anti-CEA8 antibody and then used as fluorescent biolabels for the immunolabeling and imaging of HeLa cells. The NIR-responsive multicolor visible light emission of these UC NPs will enable potential applications in biolabeling and multiplexed analysis because NIR light can penetrate tissue as deep as several inches and is safe to human body.
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Expression and prognostic role of Spy1 as a novel cell cycle protein in hepatocellular carcinoma.
Exp. Mol. Pathol.
PUBLISHED: 01-26-2009
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Spy1 is a novel cell cycle regulatory gene, which can control cell proliferation and survival through the atypical activation of cyclin-dependent kinases. Recent studies suggested that deregulation of Spy1 expression plays a key role in oncogenesis. To investigate the potential roles of Spy1 in hepatocellular carcinoma (HCC), expression of Spy1 was examined in human HCC samples.
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Mandibular angle ostectomy for Chinese women: approaches and extent determined by cephalometric analysis.
J Craniofac Surg
PUBLISHED: 01-24-2009
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Giving a square and muscular appearance, a prominent mandibular angle is considered to be unattractive in the Orient. Because of the different aesthetic sensitivities, the problem is reported more frequently in the Orient than that in the West. In most reports, the final choice of surgical procedure, including the approach, position of ostectomy, and volume of bone to be cut, depended subjectively on the experience of the surgeon and the desire of the patient. This article provides a study to make the surgical procedure accurately and objectively, involving 46 female patients asking for reduction of prominent mandibular angle for cosmetic reasons. Measurement and analysis of cephalometric radiographs were performed preoperatively. According to the different characteristics of the prominent mandibular angle in front and lateral views of the radiographs, the patients were classified into 4 types. In each type, ostectomy of different extent via different approaches or masseter botulinum toxin A injection only was given. Postoperative cephalometric analysis was also made to evaluate the result objectively. The results have been generally satisfactory.
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H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs.
Nat. Genet.
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The induction of pluripotent stem cells (iPSCs) by defined factors is poorly understood stepwise. Here, we show that histone H3 lysine 9 (H3K9) methylation is the primary epigenetic determinant for the intermediate pre-iPSC state, and its removal leads to fully reprogrammed iPSCs. We generated a panel of stable pre-iPSCs that exhibit pluripotent properties but do not activate the core pluripotency network, although they remain sensitive to vitamin C for conversion into iPSCs. Bone morphogenetic proteins (BMPs) were subsequently identified in serum as critical signaling molecules in arresting reprogramming at the pre-iPSC state. Mechanistically, we identified H3K9 methyltransferases as downstream targets of BMPs and showed that they function with their corresponding demethylases as the on/off switch for the pre-iPSC fate by regulating H3K9 methylation status at the core pluripotency loci. Our results not only establish pre-iPSCs as an epigenetically stable signpost along the reprogramming road map, but they also provide mechanistic insights into the epigenetic reprogramming of cell fate.
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Carbon and clay nanoparticles induce minimal stress responses in gram negative bacteria and eukaryotic fish cells.
Environ. Toxicol.
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We investigated in vitro the potential mutagenic and toxic effects of two clay-based nanoparticles, Cloisite® Na(+) (Cloisite) and halloysite; and multi-walled carbon nanotubes (MWCNT), commonly used in the polymer composite industry. Using the Ames test, the three nanoparticles did not have a true mutagenic effect, although growth of Salmonella enterica var. Typhimurium (S.typhimurium) was diminished at higher nanoparticle concentrations. We investigated the impact of nanoparticles on Escherichia coli and S. typhimurium including oxyR and rpoS mutants, which are susceptible to oxidative stress. The oxyR mutants were inhibited in the presence of nanoparticles, when grown aerobically with light. Toxicity was not observed in the absence of light or during anaerobic growth. E. coli rpoS mutants exhibited some toxicity when cultured with Cloisite and MWCNT only when grown aerobically with light. There was no effect with other nanoparticles, or with S. typhimurium rpoS mutants. MWCNT exhibited a slight toxic effect against Epithelioma papulosum cyprini (EPC) cells only at the highest concentration tested. There was no discernable toxicity to EPC cells caused by the clay nanoparticles. We conclude that clay-based nanoparticles and MWCNT do not exert a mutagenic effect and do not have a general toxic effect across all bacterial species or between prokaryotic and eukaryotic cells. Modest toxicity was only observed in eukaryotic EPC cells against MWCNT at the highest concentration tested. Limited species-specific toxicity to clay based and MWCNT nanoparticles was seen in bacterial strains primarily due to culture conditions and mutations that exacerbate oxidative stress. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.
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Masseter-to-facial nerve transfer: is it possible to rehabilitate the function of both the paralyzed eyelid and the oral commissure?
Aesthetic Plast Surg
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This report addresses the efficiency of masseter-to-facial nerve transfer and investigates the patients ability to perform the functions of eyelid closure and smile movements independently.
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Effects of low-order atmosphere-turbulence aberrations on the entangled orbital angular momentum states.
Opt Lett
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Based on Zernike-model expansion of turbulence phase aberrations and non-Kolmogorov spectrum model of index-of-refraction fluctuation, we analyze the effects of low-order Zernike turbulence aberrations on orbital angular momentum (OAM) entanglement states in a weak fluctuation region. The signal photon detection probability of OAM entanglement states propagating in a slant turbulence channel with non-Kolmogorov turbulence Z-tilt, defocus, astigmatism, and coma aberrations are modeled, respectively. The results demonstrate that turbulence Z-tilt aberration is the dominant aberration, coma is the second, and astigmatism is the third, but that the defocus aberration has no impact on the detection probability. As the power-law exponent of the non-Kolmogorov spectrum increases from 3 to 4, the detection probability decreases.
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Discovery of small-molecule interleukin-2 inhibitors from a DNA-encoded chemical library.
Chemistry
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Libraries of chemical compounds individually coupled to encoding DNA tags (DNA-encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high-quality DNA-encoded chemical library comprising 30,000 drug-like compounds; this was screened in 170 different affinity capture experiments. High-throughput sequencing allowed the evaluation of 120?million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor-associated antigen carbonic anhydrase?IX (CA?IX) and the pro-inflammatory cytokine interleukin-2 (IL-2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL-2 was confirmed by molecular docking. Our findings suggest that DNA-encoded chemical libraries allow the facile identification of drug-like ligands principally to any protein of choice, including molecules capable of disrupting high-affinity protein-protein interactions.
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A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population.
PLoS ONE
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Recently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.