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Find video protocols related to scientific articles indexed in Pubmed.
Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation.
Learn. Mem.
PUBLISHED: 12-01-2014
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Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP-LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories.
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Resveratrol Attenuates Intermittent Hypoxia-Induced Macrophage Migration to Visceral White Adipose Tissue and Insulin Resistance in Male Mice.
Endocrinology
PUBLISHED: 11-19-2014
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Chronic intermittent hypoxia during sleep (IH), as occurs in sleep apnea, promotes systemic insulin resistance. Resveratrol (Resv) has been reported to ameliorate high-fat diet induced obesity, inflammation, and insulin resistance. To examine the effect of Resv on IH-induced metabolic dysfunction, male mice were subjected to IH or room air (RA) conditions for 8 weeks, and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin, and leptin were obtained, HOMA levels were calculated, and insulin sensitivity tests (phosphorylated AKT/total AKT) were performed in 2 visceral white adipose tissue (VWAT) depots (epididymal (Epi) and mesenteric (Mes)) along with FACS assessments for VWAT macrophages and phenotypes (M1 and M2). IH-Veh and IH-Resv mice showed initial reductions in food intake with later recovery, with resultant lower body weights after 8 weeks, but with IH-Resv showing better increases in body weight vs. IH-Veh. IH-Veh and IH-Resv mice exhibited lower fasting glucose levels, but only IH-Veh had increased HOMA vs. all 3 other groups. Leptin levels were preserved in IH-Veh but were significantly lower in IH-Resv. Reduced VWAT p-AKT/AKT responses to insulin emerged in both Mes and Epi in IH-Veh but normalized in IH-Resv. Increases total macrophage counts and in M1:M2 ratios occurred in IH-Veh Mes and Epi compared all other 3 groups. Thus, resveratrol ameliorates food intake and weight gain during IH exposures, and markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy for metabolic morbidity in the context of sleep apnea.
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Hybrid optical fiber Fabry-Perot interferometer for simultaneous measurement of gas refractive index and temperature.
Appl Opt
PUBLISHED: 11-18-2014
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We present a hybrid miniature optical fiber Fabry-Perot interferometer for simultaneous measurement of gas refractive index and temperature. The interferometer is fabricated by cascading two short sections of capillary tubes with different inner diameters. One extrinsic interferometer is based on the air gap cavity formed by the capillary tube with large diameter. Another section of capillary tube with small inner diameter performs as an intrinsic interferometer and also provides a channel enabling gas to enter and leave the extrinsic cavity freely. The experiment shows that the different dips or peaks in fringe exhibit different responses to the changes in gas refractive index and temperature. Owing to this feature, simultaneous measurement of the gas refractive index and temperature can be realized.
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Comparison of waveguide properties and Raman spectroscopic visualization of C and O ion implantation on LaAlO3 crystals.
Appl Opt
PUBLISHED: 11-18-2014
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LaAlO3 crystals were implanted by C ions and O ions at an energy of 6.0 MeV with a fluence of 1.5×1015??ions/cm2. The profiles of the guided modes were measured through prism coupling and end-face coupling methods with a 633 nm laser source. A nonleaky waveguide structure in the TM mode was fabricated by O ion implantation after a proper annealing treatment. Characteristics of the implanted C and O ions were compared. Some changes of the full width at half of the maximum and intensity of the Raman spectra were observed between the waveguide and substrate regions in LaAlO3 crystals. Thus, the Raman spectra can be used to visualize any damage or defects in the LaAlO3 crystals during the implantation process.
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Association between Polymorphisms of Interleukin-17A and Interleukin-17F Genes and Silicosis Susceptibility in Chinese Han People.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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To explore the relationship between polymorphisms of interleukin17 (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor for lung cancer.
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Chronic sleep fragmentation induces endothelial dysfunction and structural vascular changes in mice.
Sleep
PUBLISHED: 11-04-2014
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Sleep fragmentation (SF) is a common occurrence and constitutes a major characteristic of obstructive sleep apnea (OSA). SF has been implicated in multiple OSA-related morbidities, but it is unclear whether SF underlies any of the cardiovascular morbidities of OSA. We hypothesized that long-term SF exposures may lead to endothelial dysfunction and altered vessel wall structure.
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The Cytotoxic and Mechanistic Effects of Aaptamine on Hepatocellular Carcinoma.
Anticancer Agents Med Chem
PUBLISHED: 10-25-2014
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Hepatocellular carcinoma (HCC) is the fifth most common form of cancer and the third most frequent cause of cancer-associated mortality worldwide. We isolated aaptamine from the marine sponge Aaptos, and synthesized derivatives of this compound. Aaptamine and synthetic derivatives displayed various biological activities. This represents the first account of studies on the effects of aaptamine and its derivatives in hepatocarcinogenesis. In this study, Cell Counting Kit (CCK8) was used to evaluate the anti-proliferative effect of aaptamine on HCC in vitro. Additionally, a subcutaneous xenograft model was used to determine if aaptamine could inhibit hepatocellular carcinoma in vivo. We also used RT-PCR and Western blot to analyze the mechanisms behind these effects. Our results showed that aaptamine has anti-proliferation effects on the cell lines LM3 and HepG2. Aaptamine also suppressed the colony-formation ability of HCC cells. We found that aaptamine treatment led to cell cycle arrest in HCC cells, reduced the expression of SOX9 and CDK2. Significant anti-tumor effects were observed in aaptamine-administered tumor-bearing mice as compared to controls. (and inhibited subcutaneous HCC xenograft development in vivo.) However, structural changes made to aaptamine yielded two derivatives for which all the effects listed above were considerably reduced as compared to the original compound aaptamine. In conclusion, aaptamine is demonstrated for the first time to inhibit liver cancer progression. The aaptamine-induced cell cycle arrest was associated with the increased binding of p21 to Cdk2-cyclin D/E complexes, inhibition of Cdk2 kinase activity in HCC cells.). Furthermore, aaptamine appears to be a promising and efficient treatment of liver cancer HCC-LM3 in vivo. We have also uncovered structural changes that might affect the biological activity. The work provides a promising drug candidate for HCC treatment.
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Experimental observation of different soliton types in a net-normal group-dispersion fiber laser.
Appl Opt
PUBLISHED: 10-17-2014
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Different soliton types are observed in a net-normal group-dispersion fiber laser based on nonlinear polarization rotation for passive mode locking. The proposed laser can deliver a dispersion-managed soliton, typical dissipation solitons, and a quasi-harmonic mode-locked pulse, a soliton bundle, and especially a dark pulse by only appropriately adjusting the linear cavity phase delay bias using one polarization controller at the fixed pump power. These nonlinear waves show different features, including the spectral shapes and time traces. The experimental observations show that the five soliton types could exist in the same laser cavity, which implies that integrable systems, dissipative systems, and dark pulse regimes can transfer and be switched in a passively mode-locked laser. Our studies not only verify the numeral simulation of the different soliton-types formation in a net-normal group-dispersion operation but also provide insight into Ginzburg-Landau equation systems.
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Increased expression of TRPV1 in the trigeminal ganglion is involved in orofacial pain during experimental tooth movement in rats.
Eur. J. Oral Sci.
PUBLISHED: 10-15-2014
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To investigate whether transient receptor potential vanilloid type 1 (TRPV1) is involved in pain induced by experimental tooth movement, experiments were performed in male Sprague-Dawley rats weighing 200-250 g. Directed face-grooming behavior was used to evaluate nocifensive behavior in rats during experimental tooth movement. The distribution of TRPV1 in the trigeminal ganglion (TG) was evaluated by immunohistochemistry, and its expression was detected by western blotting at several time points following the application of various magnitudes of force during tooth movement. Immunohistochemical analysis revealed that TRPV1 was expressed in TG, and its expression was increased after experimental tooth movement. Western blot results also showed that experimental tooth movement led to a statistically significant increase in expression of TRPV1 protein in TG. Meanwhile, the time spent on directed face-grooming peaked on day 1 and thereafter showed a gradual decrease. In addition, both the change in TRPV1 expression in the TG and directed face-grooming behavior were modulated in a force-dependent manner and in concert with initial orthodontic pain responses. Our results reveal that TRPV1 expression is modulated by experimental tooth movement and is involved in tooth-movement pain.
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Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist.
Molecules
PUBLISHED: 10-09-2014
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The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.
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Inhibition of Histone Deacetylase by Butyrate Protects Rat Liver from Ischemic Reperfusion Injury.
Int J Mol Sci
PUBLISHED: 09-25-2014
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We showed previously that pretreatment of butyrate, which is an endogenous histone deacetylase (HDAC) inhibitor normally fermented from undigested fiber by intestinal microflora, seriously alleviated ischemia reperfusion (I/R)-induced liver injury by inhibiting the nuclear factor ?B (NF-?B) pathway. The goal of this study was to investigate the effect of butyrate administrated at the onset of ischemia for HDAC inhibition in hepatic I/R injury. Sprague Dawley rats were subjected to warm ischemia for 60 min followed by 6 and 24 h of reperfusion. Butyrate was administrated at the onset of ischemia. Liver injury was evaluated by serum levels of aminotransferase, inflammatory factors, and histopathology. The levels of acetylated histone H3 and expression of heat shock protein (Hsp) 70 were measured by Western blot. After reperfusion, the levels of acetylated histone H3 significantly decreased. Butyrate treatment markedly prevented the reduction of acetylated histone H3 and upregulated the expression of Hsp70, thereby reducing liver injury. Our study demonstrated that I/R resulted in marked reduction of histone acetylation; butyrate exerted a great hepatoprotective effect through HDAC inhibition and Hsp70 induction.
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Porous Liquids: A Promising Class of Media for Gas Separation.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-24-2014
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A porous liquid containing empty cavities has been successfully fabricated by surface engineering of hollow structures with suitable corona and canopy species. By taking advantage of the liquid-like polymeric matrices as a separation medium and the empty cavities as gas transport pathway, this unique porous liquid can function as a promising candidate for gas separation. Moreover, such a facile synthetic strategy can be further extended to the fabrication of other types of nanostructure-based porous liquid, opening up new opportunities for preparation of porous liquids with attractive properties for specific tasks.
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Temperature-independent fiber inclinometer based on orthogonally polarized modes coupling using a polarization-maintaining fiber bragg grating.
Sensors (Basel)
PUBLISHED: 09-24-2014
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A reflection fiber inclinometer is proposed and experimentally demonstrated based on two linearly polarized (LP) modes coupling. The configuration consists of a section of polarization-maintaining fiber (PMF) containing a fiber Bragg grating (FBG) splicing with single mode fiber (SMF). Bending the PMF in the upstream of FBG can induce an additional birefringence of PMF, which results in the intensity changes of two LP modes owing to orthogonal polarization coupling. The experimental results represent that the device shows different bending responses at the angle range from 0° to 40°and from 64° to 88°, respectively. Moreover, the temperature change just shifts the wavelengths of LP modes reflected and does not influence their intensities, which effectively avoid the temperature cross-sensitivity and make it a good candidate for measuring inclinometer and temperature simultaneously.
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Anti-inflammatory mechanism research of tanshinone II A by module-based network analysis.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Tanshinone IIA (Tan IIA) is one of the major fat-soluble ingredients in Salvia miltiorrhiza which has been widely used for various inflammatory conditions associated with cardiovascular and cerebrovascular disorders. However, the underlying anti-inflammatory mechanisms of Tan IIA are incompletely understood. The purpose of this study was to illuminate the anti-inflammatory mechanism of Tan IIA based on the protein interaction network (PIN) analysis. A PIN of Tan IIA was constructed with 281 nodes and 814 interactions and analyzed by gene ontology (GO) enrichment analysis based on Markov Cluster algorithm (MCL). Three modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of Tan IIA may be partly attributable to the mediate activation of TRAF2, TRAF3 and TRAF6, to inhibit the toll-like receptor signaling pathway and combine with AGER. Therefore, the module-based network analysis approach will be a new method for better understanding the anti-inflammatory mechanism of Tan IIA.
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Role of Kinase Epidermal Growth Factor Receptor and SRC in the Caerulein-Induced Acute Pancreatitis in Mice.
Pancreas
PUBLISHED: 09-16-2014
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In this study, we identified the protein kinases that play the most distinct roles in the occurrence of acute pancreatitis (AP).
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Detection and diagnosis of iatrogenic inadvertent diversion of partial inferior vena cava into the left atrium by transesophageal echocardiography during large posteroinferior surgical atrial septal defect closure.
J Anesth
PUBLISHED: 09-12-2014
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Iatrogenic diversion of the inferior vena cava (IVC) into the left atrium (LA) is usually reported as a rare complication following large posteroinferior atrial septal defect (ASD) surgery. It may cause acute or chronic hypoxemia, and other potentially life-threatening complications such as stroke. We present a case in which the ASD patch straddled the IVC entrance diagnosed immediately by transesophageal echocardiography (TEE) during the period of patient separated from cardiopulmonary bypass, avoiding the related complications. Our report further underlines the important role of TEE to monitor and guide ASD surgical management, especially secundum ASD with inferior extension or inferior sinus venosus defects, for the early diagnosis of iatrogenic surgical errors.
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Syndrome in question.
An Bras Dermatol
PUBLISHED: 09-04-2014
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Vulvovaginal-gingival syndrome is characterized by erosions and desquamation of the vulva, vagina, and gingiva. We reported a case of a 32-year-old woman presenting with an 8-year history of damage to the vulval and perianal anatomy and limitation of mouth opening. The patient's symptoms were relieved after treatment with topical tacrolimus cream.
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Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion.
PLoS ONE
PUBLISHED: 08-29-2014
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Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.
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Meta-analysis of best corrected visual acuity after treatment for myopic choroidal neovascularisation.
Int J Ophthalmol
PUBLISHED: 08-18-2014
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To compare the best corrected visual acuity (BCVA) between Verteporfin with photodynamic therapy (PDT) and intravitreal anti-vascular endothelial growth factor (anti-VEGF) in patients with myopic choroidal neovascularization (CNV).
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Interactions of Borneol with DPPC Phospholipid Membranes: A Molecular Dynamics Simulation Study.
Int J Mol Sci
PUBLISHED: 08-15-2014
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Borneol, known as a "guide" drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol's penetration enhancing effect, the molecular basis of its action on bio-membranes is still unclear. We carried out a series of coarse-grained molecular dynamics simulations with the borneol concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis) to study the interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3-phosphatidylcholine) bilayer membrane, and the temperature effects were also considered. At concentrations below 21.89%, borneol's presence only caused DPPC bilayer thinning and an increase in fluidity; A rise in temperature could promote the diffusing progress of borneol. When the concentration was 21.89% or above, inverted micelle-like structures were formed within the bilayer interior, which led to increased bilayer thickness, and an optimum temperature was found for the interaction of borneol with the DPPC bilayer membrane. These findings revealed that the choice of optimal concentration and temperature is critical for a given application in which borneol is used as a penetration enhancer. Our results not only clarify some molecular basis for borneol's penetration enhancing effects, but also provide some guidance for the development and applications of new preparations containing borneol.
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Lab-in-a-shell: encapsulating metal clusters for size sieving catalysis.
J. Am. Chem. Soc.
PUBLISHED: 08-01-2014
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Here we describe a lab-in-a-shell strategy for the preparation of multifunctional core-shell nanospheres consisting of a core of metal clusters and an outer microporous silica shell. Various metal clusters (e.g., Pd and Pt) were encapsulated and confined in the void space mediated by the entrapped polymer dots inside hollow silica nanospheres acting first as complexing agent for metal ions and additionally as encapsulator for clusters, limiting growth and suppressing the sintering. The Pd clusters encapsulated in hybrid core-shell structures exhibit exceptional size-selective catalysis in allylic oxidations of substrates with the same reactive site but different molecular size (cyclohexene ?0.5 nm, cholesteryl acetate ?1.91 nm). The solvent-free aerobic oxidation of diverse hydrocarbons and alcohols was further carried out to illustrate the benefits of such an architecture in catalysis. High activity, outstanding thermal stability and good recyclability were observed over the core-shell nanocatalyst.
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Intrinsic Fabry-Perot interferometeric sensor based on microfiber created by chemical etching.
Sensors (Basel)
PUBLISHED: 07-17-2014
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An intrinsic Fabry-Perot interferometeric sensor based on a microfiber has been demonstrated. The micro-size suspended core is created by chemical etching a photonics crystal fiber, of which the cladding has a micrometer-spaced, hexagonal array of air holes. The sensing head is fabricated by chemical etching a short section of photonics crystal fiber spliced with a single mode fiber. The temperature sensing characteristic of the interferometer has also been demonstrated and a sensitivity 14.3 pm/°C is obtained.
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Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice.
Environ. Toxicol.
PUBLISHED: 07-12-2014
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To investigate the protective effect of testosterone propionate (TP) on reproductive toxicity caused by endosulfan in male mice, three group experiments were designed: the control group received 0 and 0, the endosulfan group received 0.8 and 0, and the endosulfan?+?TP group received 0.8 mg/kg/d endosulfan and 10 mg/kg/d TP, respectively. The results showed that TP significantly prevented the declines of concentration and motility rates in sperm, reduced the rate of sperm abnormalities in epididymis; and antagonized the decreases in spermatogenous cell and sperm numbers in testes induced by endosulfan. TP also decreased the numbers of cavities formed, prevented the decreases of plasma testosterone and androgen receptor (AR) mRNA in testicular tissue, alleviated the increase of LH induced by endosulfan. It is likely that TP relieve the reproductive toxicity by reversing the endosulfan-induced decreases in testosterone secretion and AR expression that resulted from the alteration of Leydig cell function. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.
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Sensitivity-improved strain sensor over a large range of temperatures using an etched and regenerated fiber Bragg grating.
Sensors (Basel)
PUBLISHED: 07-11-2014
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A sensitivity-improved fiber-optic strain sensor using an etched and regenerated fiber Bragg grating (ER-FBG) suitable for a large range of temperature measurements has been proposed and experimentally demonstrated. The process of chemical etching (from 125 µm to 60 µm) provides regenerated gratings (at a temperature of 680 °C) with a stronger reflective intensity (from 43.7% to 69.8%), together with an improved and linear strain sensitivity (from 0.9 pm/?? to 4.5 pm/??) over a large temperature range (from room temperature to 800 °C), making it a useful strain sensor for high temperature environments.
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Mechanism of action of salvianolic acid B by module-based network analysis.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Salvianolic Acid B (Sal B) is one of the main medicinal ingredients of Radix Salvia miltiorrhiza (Danshen) and possesses a variety of pharmacological effects. The purpose of this study was to discover the new mechanism of action of Sal B based on the protein interaction network (PIN) analysis. A PIN of Sal B was constructed with 852 nodes and 8,626 interactions. By fast agglomerate algorithm based on the edge clustering coefficients (FAG-EC), 11 modules were detected from the network. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of Sal B played in cardiovascular disease were related to multiple biological processes, which could represent the characteristics of Chinese Material Medica (CMM) as a whole to regulate the disease. The most interesting finding of this work was that the anti-inflammatory effect of Sal B was due to the immune response of T lymphocytes by regulating IL-2 family, CD3E, CD79A, MAP3K7 and PRKCQ. Therefore, the module-based network analysis will be an effective method for better understanding CMM.
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A combination of pharmacophore modeling, molecular docking and virtual screening for iNOS inhibitors from Chinese herbs.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover new iNOS inhibitors. This study was performed to identify natural iNOS inhibitors from traditional Chinese herbs through a combination of pharmacophore modeling, molecular docking and virtual screening. First, the pharmacophore models were generated though six known iNOS inhibitors and validated by a test database. The pharmacophore model_017 showed good performance in external validation and was employed to screen Traditional Chinese Medicine Database (Version 2009), which resulting in a hit list of 498 compounds with matching score (QFIT) above 40. Then, the hits were subjected to molecular docking for further refinement. An empirical scoring function was used to evaluate the affinity of the compounds and the target protein. Parts of compounds with high docking scores have been reported to have the related pharmacological activity from the literatures. The results provide a set of useful guidelines for the rational discovery of natural iNOS inhibitors from Chinese herbs.
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Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells.
Oncotarget
PUBLISHED: 06-23-2014
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Endoplasmic reticulum stress from unfolded proteins is associated with the proliferation of pancreatic tumor cells, making the many regulatory molecules of this pathway appealing targets for therapy. The objective of our study was to assess potential therapeutic efficacy of inhibitors of unfolded protein response (UPR) in pancreatic cancers focusing on IRE1? inhibitors. IRE1?-mediated XBP-1 mRNA splicing encodes a transcription factor that enhances transcription of chaperone proteins in order to reverse UPR. Proliferation assays using a panel of 14 pancreatic cancer cell lines showed a dose- and time-dependent growth inhibition by IRE1?-specific inhibitors (STF-083010, 2-Hydroxy-1-naphthaldehyde, 3-Ethoxy-5,6-dibromosalicylaldehyde, toyocamycin). Growth inhibition was also noted using a clonogenic growth assay in soft agar, as well as a xenograft in vivo model of pancreatic cancer. Cell cycle analysis showed that these IRE1? inhibitors caused growth arrest at either the G1 or G2/M phases (SU8686, MiaPaCa2) and induced apoptosis (Panc0327, Panc0403). Western blot analysis showed cleavage of caspase 3 and PARP, and prominent induction of the apoptotic molecule BIM. In addition, synergistic effects were found between either STF-083010, 2-Hydroxy-1-naphthaldehyde, 3-Ethoxy-5,6-dibromosalicylaldehyde, or toyocamycin and either gemcitabine or bortezomib. Our data suggest that use of an IRE1? inhibitor is a novel therapeutic approach for treatment of pancreatic cancers.
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Erythropoietin promotes retinal angiogenesis in a mouse model.
Mol Med Rep
PUBLISHED: 06-17-2014
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This study aimed to investigate the effect and potential mechanisms of exogenous administration of recombinant human erythropoietin (rhEPO) on retinal angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). Postnatal day 7 (P7) mice (n=132) were randomly assigned to one of six groups: Control group (n=22), OIR group (n=22), OIR + vehicle control group (n=22), OIR + rhEPO 10 IU group (n=22), OIR + rhEPO 50 IU group (n=22), and OIR + rhEPO 100 IU group (n=22). OIR was induced by exposing mice to 75±2% O2 for five days, followed by exposure to room air for a further five days. Animals in groups 3-6 (the OIR + vehicle control group and OIR + rhEPO 10 IU, 50 IU, and 100 IU groups) received an intraperitoneal injection of saline, or rhEPO 10 IU, 50 IU and 100 IU, respectively, which were administered daily from P7-P12. Immunofluorescent and hematoxylin-eosin staining were used to detect retinal neovascularization (RNV) in retinal whole mounts. Quantitative polymerase chain reaction and western blot analysis were used to detect the expression levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS). RNV occurred in the OIR groups and was accompanied by dilated, twisted and occluded blood vessels. rhEPO treatment resulted in an increase in the number of newly formed and severely dilated vessels. rhEPO increased RNV in a dose-dependent manner, which was accompanied by an increase in the messenger RNA and protein expression of VEGF, eNOS and nNOS. Thus, exogenous use of rhEPO promotes the RNV in a mouse model of OIR and is accompanied by increased expression levels of VEGF, eNOS and nNOS.
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SETDB1 accelerates tumorigenesis by regulating WNT signaling pathway.
J. Pathol.
PUBLISHED: 06-03-2014
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We investigated the oncogenic role of SETDB1 focusing on non-small cell lung cancer (NSCLC) having high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry, 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p?
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A thermally annealed Mach-Zehnder interferometer for high temperature measurement.
Sensors (Basel)
PUBLISHED: 05-23-2014
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An in-fiber Mach-Zehnder interferometer (MZI) for high temperature measurement is proposed and experimentally demonstrated. The device is constructed of a piece of thin-core fiber (TCF) sandwiched between two short sections of multimode fiber (MMF), i.e., a MMF-TCF-MMF structure. A well-defined interference spectrum is obtained owing to the core-mismatch, and the interference dips are sensitive to the ambient temperature. The experimental results show that the proposed interferometer is capable of high temperature measurement up to 875 °C with a sensitivity of 92 pm/°C over repeated measurements. The explored wavelength drop point may limit the measurement range, which can be improved by repeated thermal annealing.
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Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 receptor-Gi protein complex.
J. Biol. Chem.
PUBLISHED: 05-22-2014
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In this study, we applied a comprehensive G protein-coupled receptor-G?i protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2 (CB2)-G?i interface and then used molecular dynamics simulations to explore the dynamics of complex formation. Three cross-link sites were identified using LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link between C3.53(134) in TMH3 and the G?i C-terminal i-3 residue Cys-351; 2) a lysine cross-link between K6.35(245) in TMH6 and the G?i C-terminal i-5 residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the G?i ?4?6 loop residue, Lys-317. To investigate the dynamics and nature of the conformational changes involved in CB2·Gi complex formation, we carried out microsecond-time scale molecular dynamics simulations of the CB2 R*·G?i1?1?2 complex embedded in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer, using cross-linking information as validation. Our results show that although molecular dynamics simulations started with the G protein orientation in the ?2-AR*·G?s?1?2 complex crystal structure, the G?i1?1?2 protein reoriented itself within 300 ns. Two major changes occurred as follows. 1) The G?i1 ?5 helix tilt changed due to the outward movement of TMH5 in CB2 R*. 2) A 25° clockwise rotation of G?i1?1?2 underneath CB2 R* occurred, with rotation ceasing when Pro-139 (IC-2 loop) anchors in a hydrophobic pocket on G?i1 (Val-34, Leu-194, Phe-196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three experimentally identified cross-links can occur. These findings should be relevant for other class A G protein-coupled receptors that couple to Gi proteins.
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Cycloastragenol, a triterpene aglycone derived from Radix astragali, suppresses the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-20-2014
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Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 value of 13.0 ?M. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 ?M. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50 value was determined as 21.9 ?M. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.
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Sleep fragmentation in mice induces nicotinamide adenine dinucleotide phosphate oxidase 2-dependent mobilization, proliferation, and differentiation of adipocyte progenitors in visceral white adipose tissue.
Sleep
PUBLISHED: 05-03-2014
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Chronic sleep fragmentation (SF) without sleep curtailment induces increased adiposity. However, it remains unclear whether mobilization, proliferation, and differentiation of adipocyte progenitors (APs) occurs in visceral white adipose tissue (VWAT), and whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2) activity plays a role.
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[Funding for division of microbiology by National Natural Science Foundation of China in 2013].
Wei Sheng Wu Xue Bao
PUBLISHED: 05-03-2014
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We provide an overview of proposals applied and projects funded by the division of microbiology, department of life sciences, National Natural Science Foundation of China in 2013,. The traits and problems in different sub-disciplines were also analyzed, which provides reference for Chinese researchers to apply funding in microbiology next year.
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Kissing nevus of the penis. Report of two cases and review of the literature.
An Bras Dermatol
PUBLISHED: 04-29-2014
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Kissing nevus is a curious type of nevus that was first described on the eyelids and rarely described on the penis. We report two cases of kissing nevus of the penis and review previously reported cases. The lesions of the kissing nevus of the penis showed characteristic mirror-image symmetry relative to the coronal sulcus. On histopathology, the lesion showed a compound nevus.
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[Blastic plasmacytoid dendritic cell neoplasm:a clinicopathologic study of 7 cases].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-26-2014
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To improve the clinicopathological understanding of blastic plasmacytoid dendritic cell neoplasm (BPDCN).
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Thiolate ligands as a double-edged sword for CO oxidation on CeO2 supported Au25(SCH2CH2Ph)18 nanoclusters.
J. Am. Chem. Soc.
PUBLISHED: 04-15-2014
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The effect of thiolate ligands was explored on the catalysis of CeO2 rod supported Au25(SR)18 (SR = -SCH2CH2Ph) by using CO oxidation as a probe reaction. Reaction kinetic tests, in situ IR and X-ray absorption spectroscopy, and density functional theory (DFT) were employed to understand how the thiolate ligands affect the nature of active sites, activation of CO and O2, and reaction mechanism and kinetics. The intact Au25(SR)18 on the CeO2 rod is found not able to adsorb CO. Only when the thiolate ligands are partially removed, starting from the interface between Au25(SR)18 and CeO2 at temperatures of 423 K and above, can the adsorption of CO be observed by IR. DFT calculations suggest that CO adsorbs favorably on the exposed gold atoms. Accordingly, the CO oxidation light-off temperature shifts to lower temperature. Several types of Au sites are probed by IR of CO adsorption during the ligand removal process. The cationic Au sites (charged between 0 and +1) are found to play the major role for low-temperature CO oxidation. Similar activation energies and reaction rates are found for CO oxidation on differently treated Au25(SR)18/CeO2 rod catalysts, suggesting a simple site-blocking effect of the thiolate ligands in Au nanocluster catalysis. Isotopic labeling experiments clearly indicate that CO oxidation on the Au25(SR)18/CeO2 rod catalyst proceeds predominantly via the redox mechanism where CeO2 activates O2 while CO is activated on the dethiolated gold sites. These results point to a double-edged sword role played by the thiolate ligands on Au25 nanoclusters for CO oxidation.
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Mesoporous Prussian blue analogues: template-free synthesis and sodium-ion battery applications.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-29-2014
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The synthesis of mesoporous Prussian blue analogues through a template-free methodology and the application of these mesoporous materials as high-performance cathode materials in sodium-ion batteries is presented. Crystalline mesostructures were produced through a synergistically coupled nanocrystal formation and aggregation mechanism. As cathodes for sodium-ion batteries, the Prussian blue analogues all show a reversible capacity of 65 mA h g-1 at low current rate and show excellent cycle stability. The reported method stands as an environmentally friendly and low-cost alternative to hard or soft templating for the fabrication of mesoporous materials.
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Identification of miRNAs involved in pear fruit development and quality.
BMC Genomics
PUBLISHED: 03-18-2014
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MicroRNAs (miRNAs) are a class of small, endogenous RNAs that take part in regulating genes through mediating gene expressions at the post-transcriptional level in plants. Previous studies have reported miRNA identification in various plants ranging from model plants to perennial fruit trees. However, the role of miRNAs in pear (Pyrus bretschneideri) fruit development is not clear. Here, we investigated the miRNA profiles of pear fruits from different time stages during development with Illumina HiSeq 2000 platform and bioinformatics analysis. Quantitative real-time PCR was used to validate the expression levels of miRNAs.
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Exploration of the mechanism of pattern-specific treatments in coronary heart disease with network pharmacology approach.
Comput. Biol. Med.
PUBLISHED: 03-15-2014
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Traditional Chinese medicine (TCM) pattern is a valuable classification method in the treatment of complex disease such as coronary heart disease (CHD). In accordance to TCM patterns, our ancestors created many pertinent TCM formulae, which have been used in China for thousands of years and are still playing an important role in China today. However, the biological mechanism of TCM pattern-specific formulae remains elusive. In this paper, we chose CHD patterns (Qi-stagnation induced blood-stasis syndrome, abbreviated as QSB; Qi-deficiency induced blood-stasis syndrome, abbreviated as QDB) as examples to illustrate the mechanism of their pattern-specific formulae. Using entity grammar systems (EGS) formalism, we built two pharmacologic networks of the formulae and obtained the intersection and difference networks by network comparison. Then we analyzed their common and different mechanisms for treating CHD by GO enrichment analysis. The results indicate that QDB-specific formula takes more special molecular paths to treat CHD, which contribute to more severe pathological changes in comparison with QSB. In this paper, we achieved a better understanding of the pharmacological characteristics of CHD patterns-specific formulae, which is beneficial to explore different therapies for a disease to enhance the effectiveness and pertinence of treatment.
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Biopharmaceutics classification of puerarin and comparison of perfusion approaches in rats.
Int J Pharm
PUBLISHED: 03-03-2014
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The present study was conducted to characterize the biopharmaceutics classification system (BCS) category of puerarin in terms of intrinsic dissolution rate (IDR) and rat intestinal permeability and to investigate the poor intestinal absorption probably related to the drug metabolism in the gut wall of rats. Equilibrium solubility of puerarin was determined in various phosphate buffers and water, and IDR was estimated by measuring the dissolution of a non-disintegrating compact. Intestinal permeability (Peff and Pblood) of puerarin was determined using the technology of in situ single-pass intestinal perfusion (SPIP) and intestinal perfusion with venous sampling (IPVS) in fasted rats. Metabolism of puerarin in intestinal tissue was tested by S9 incubation in vitro. The aqueous solubility of puerarin in phosphate buffers and water was good with a maximum solubility of 7.56 mg/mL at pH 7.4. Obtained IDR values of puerarin were in the range of 0.360-1.088 mg/min/cm(2), with maximum and minimum IDR value of pH 7.4 and pH 4.0, respectively. The Peff was 1.252 × 10(-5)cm/s determined by SPIP and the Pblood was 0.068×10(-5)cm/s by IPVS in jejunum at puerarin 80 ?g/mL. The metabolism rate of puerarin determined by the intestinal S9 fraction indicated that the gut wall metabolism of puerarin is one cause of poor absorption. According to the proposed classification of drugs and the results obtained from equilibrium solubility, IDR, Peff and Pblood, it is concluded that puerarin could be categorized IV drug of the BCS based on its low solubility and low intestinal permeability values.
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Modular analysis of bioinformatics demonstrates a critical role for NF-?B in macrophage activation.
Inflammation
PUBLISHED: 03-01-2014
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To achieve the goal of identifying the gene groups that regulated macrophage activation, a total of 925 differentially expressed genes of activated macrophages were found at the intersection of the three series (GSE5099-1, GSE5099-2, and GSE18686) from the Gene Expression Omnibus (GEO) database, and a sub-network was constructed based on the protein-protein interaction (PPI) network. Four communities (K?=?3) were identified from the sub-network using the CFinder software. Community 1 was considered as the gene group of interest base on the heat map. GO-BP and KEGG enrichment analysis with the DAVID software showed that the functions of the 14 genes in community 1 were mainly related to the NF-?B pathway. A network was constructed using the Cytoscape software. The diagram showed that STAT1, NFKBIA, NFKAIB, JUN, and RELA were the key genes in the regulation of macrophage activation. Among these genes, RELA (NF-?B P65) was an important member of the NF-?B family, while NFKBIA (I?B?) and NFKAIB (I?B?) were the inhibitory factors of NF-?B. Small molecules capable of regulating these five genes were identified via the CMap software, and a network diagram was generated using the Cytoscape software to provide a reference for the development of new drugs that regulate macrophage activation.
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Bioinformatics screening regarding herbal components that targetedly regulate the function of tumour-associated macrophages.
Oncol. Rep.
PUBLISHED: 02-26-2014
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As an important component of tumour stroma, tumour-associated macrophages (TAMs) promote tumour development and progression. Herbs have been increasingly used in anticancer therapies due to their wide-ranging anticancer effects and minor side-effects. However, no herb-based treatments targeting TAMs have yet been proposed. To address this issue, screening using modular analysis bioinformatics techniques found 6 core functional modules for TAMs that contain 46 total genes. Moreover, 15 potential new anticancer drugs that regulate the genes in the 6 core modules were identified through bioinformatics techniques and Fisher's exact test. Our results provide a new research avenue for targeting TAMs in anticancer therapies.
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Comparison of two approaches of intestinal absorption by puerarin.
J Pharmacol Toxicol Methods
PUBLISHED: 02-23-2014
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Everted gut sac (EGS) and in situ single-pass intestinal perfusion (SPIP) have been widely used in the study of drug absorption and biopharmaceutical classification systems (BCS). Furthermore, they could also be applied in the research of drug intestinal first-pass metabolism. Since most of Chinese herbal medicines (CHMs) are orally administrated, it is necessary to study the permeability of active ingredients of CHMs. Thus, we attempted to apply the EGS and SPIP models to study the permeability of puerarin, one of the active marker compounds (AMCs) of Puerariae Radix.
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Characterization of rational biomarkers accompanying fever in yeast-induced pyrexia rats using urine metabolic footprint analysis.
J Pharm Biomed Anal
PUBLISHED: 02-13-2014
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Fever is a prominent feature of diseases and is an ongoing process that is always accompanied by metabolic changes in the body system. Despite the success of temperature regulation theory, the underlying biological process remains unclear. To truly understand the nature of the febrile response, it is crucial to confirm the biomarkers during the entire biological process. In the current study, a 73-h metabolic footprint analysis of the urine from yeast-induced pyrexia rats was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Potential biomarkers were selected using orthogonal partial least squares-discriminate analysis (OPLS-DA), the rational biomarkers were verified by Pearson correlation analysis, and the predictive power was evaluated using receiver operator characteristic (ROC) curves. A metabolic network constructed using traditional Chinese medicine (TCM) grammar systems was used to validate the rationality of the verified biomarkers. Finally, five biomarkers, including indoleacrylic acid, 3-methyluridine, tryptophan, nicotinuric acid and PI (37:3), were confirmed as rational biomarkers because their correlation coefficients were all greater than 0.87 and because all of the correlation coefficients between any pair of these biomarkers were higher than 0.75. The areas under the ROC curves were all greater than 0.84, and their combined predictive power was considered reliable because the greatest area under the ROC curve was 0.968. A metabolic network also demonstrated the rationality of these five biomarkers. Therefore, these five metabolites can be adopted as rational biomarkers to reflect the process of the febrile response in inflammation-induced pyrexia.
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N -methyl- N -nitrosourea-induced retinal degeneration in mice.
Exp. Eye Res.
PUBLISHED: 02-07-2014
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Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
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N-acetylcysteine alleviated silica-induced lung fibrosis in rats by down-regulation of ROS and mitochondrial apoptosis signaling.
Toxicol. Mech. Methods
PUBLISHED: 01-20-2014
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Reactive oxygen species (ROS) is a normal metabolic product of cellular respiration, but too much ROS can induce cell apoptosis. Here, we used N-acetylcysteine (NAC) to inhibit ROS activity to explore the effects of NAC on silica-induced pulmonary fibrosis in rats and provide evidence for study on the mechanism of silicosis. 24 adult male Sprague-Dawley rats weighing 180-220 g were randomly divided into three groups with eight rats in each group. Silicosis model group and NAC group were adopted non-tracheal exposure method of disposable intrapulmonary injection of 50 g/L, silica suspension 1 mL to establish animal silicosis model, NAC group treated with 600 mg/kg NAC by gavage from the right day of modeling, all animals were sacrificed after 28 days. The level of ROS contents and mitochondrial transmembrane potential changes of AM, the mRNA expression level of type I and type III procollagen, cytochrome C, cysteinyl aspartate specific protease-9 and caspase-3 were detected. The severity of pathological changes and pulmonary fibrosis were observed by pathologic specimens. It was showed that ROS contents and MTP changes were lower in the NAC group compared with the silicosis model group, other indexes were lower in the NAC group than the model group, but higher than those of the control group, the degree of lung fibrotic lesions observed from the pathological slices showed the same trend. These data indicated that NAC can reduce ROS content of AM in silica exposure rats, the mitochondrial apoptosis pathway can also be inhibited, the severity of pulmonary fibrosis alleviated as a result.
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Effects of MicroRNA-10b on lung cancer cell proliferation and invasive metastasis and the underlying mechanism.
Asian Pac J Trop Med
PUBLISHED: 01-15-2014
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To study the influence of MicroRNA-10b on proliferation and invasion of human low metastatic lung cancer cell 95-C and its mechanism.
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Characterization of the lipoxygenase (LOX) gene family in the Chinese white pear (Pyrus bretschneideri) and comparison with other members of the Rosaceae.
BMC Genomics
PUBLISHED: 01-13-2014
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Lipoxygenases (LOXs), a type of non-haem iron-containing dioxygenase, are ubiquitous enzymes in plants and participate in the formation of fruit aroma which is a very important aspect of fruit quality. Amongst the various aroma volatiles, saturated and unsaturated alcohols and aldehydes provide the characteristic aroma of the fruit. These compounds are formed from unsaturated fatty acids through oxidation, pyrolysis and reduction steps. This biosynthetic pathway involves at least four enzymes, including LOX, the enzyme responsible for lipid oxidation. Although some studies have been conducted on the LOX gene family in several species including Arabidopsis, soybean, cucumber and apple, there is no information from pear; and the evolutionary history of this gene family in the Rosaceae is still not resolved.
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Investigating the cellular fate of a DNA-targeted platinum-based anticancer agent by orthogonal double-click chemistry.
J. Biol. Inorg. Chem.
PUBLISHED: 01-10-2014
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Confocal fluorescence microscopy was used to study a platinum-based anticancer agent in intact NCI-H460 lung cancer cells. Orthogonal copper-catalyzed azide-alkyne cycloaddition (click) reactions were used to simultaneously determine the cell-cycle-specific localization of the azide-functionalized platinum-acridine agent 1 and monitor its effects on nucleic acid metabolism. Copper-catalyzed postlabeling showed advantages over copper-free click chemistry using a dibenzocyclooctyne (DIBO)-modified reporter dye, which produced high background levels in microscopic images and failed to efficiently label platinum adducts in chromatin. Compound 1 was successfully labeled with the fluorophore DIBO to yield 1* (characterized by in-line high-performance liquid chromatography/electrospray mass spectrometry). 1 and 1* show a high degree of colocalization in the confocal images, but the ability of 1* to target the (compacted) chromatin was markedly reduced, most likely owing to the steric bulk introduced by the DIBO tag. Nuclear platinum levels correlated inversely with the ability of the cells to synthesize DNA and cause cell cycle arrest, as confirmed by bivariate flow cytometry analysis. In addition, a decrease in the level of cellular transcription, shrinkage of the nucleolar regions, and redistribution of RNA into the cytosol were observed. Postlabeling in conjunction with colocalization experiments is a useful tool for studying the cell killing mechanism of this type of DNA-targeted agent.
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Paxillin regulates vascular endothelial growth factor A-induced in vitro angiogenesis of human umbilical vein endothelial cells.
Mol Med Rep
PUBLISHED: 01-09-2014
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The purpose of the present study was to investigate the role of paxillin in the vascular endothelial growth factor A (VEGF?A)?induced adhesion, proliferation, migration and capillary formation of endothelial cells (ECs) in vitro. Human umbilical vein ECs (HUVECs) were used to evaluate these four processes in vitro. The HUVECs were either mock?transfected (control), transfected with scramble small interference RNA (siRNA) or transfected with siRNA specifically targeting paxillin. VEGF?A (20 ng/ml) was used to stimulate angiogenesis. The VEGF?A treatment significantly increased the adhesion, proliferation, migration and tube formation of the HUVECs in the control and scramble siRNA groups, whereas the siRNA?-mediated knockdown of paxillin inhibited these VEGF?A?induced effects. Paxillin is essential for VEGF?A?mediated angiogenesis in ECs and its inhibition may be a potential target for antiangiogenic therapies.
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Polymeric molecular sieve membranes via in situ cross-linking of non-porous polymer membrane templates.
Nat Commun
PUBLISHED: 01-09-2014
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High-performance polymeric membranes for gas separation are attractive for molecular-level separations in industrial-scale chemical, energy and environmental processes. Molecular sieving materials are widely regarded as the next-generation membranes to simultaneously achieve high permeability and selectivity. However, most polymeric molecular sieve membranes are based on a few solution-processable polymers such as polymers of intrinsic microporosity. Here we report an in situ cross-linking strategy for the preparation of polymeric molecular sieve membranes with hierarchical and tailorable porosity. These membranes demonstrate exceptional performance as molecular sieves with high gas permeabilities and selectivities for smaller gas molecules, such as carbon dioxide and oxygen, over larger molecules such as nitrogen. Hence, these membranes have potential for large-scale gas separations of commercial and environmental relevance. Moreover, this strategy could provide a possible alternative to 'classical' methods for the preparation of porous membranes and, in some cases, the only viable synthetic route towards certain membranes.
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Protein Network Signatures Associated with Exogenous Biofuels Treatments in Cyanobacterium Synechocystis sp. PCC 6803.
Front Bioeng Biotechnol
PUBLISHED: 01-01-2014
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Although recognized as a promising microbial cell factory for producing biofuels, current productivity in cyanobacterial systems is low. To make the processes economically feasible, one of the hurdles, which need to be overcome is the low tolerance of hosts to toxic biofuels. Meanwhile, little information is available regarding the cellular responses to biofuels stress in cyanobacteria, which makes it challenging for tolerance engineering. Using large proteomic datasets of Synechocystis under various biofuels stress and environmental perturbation, a protein co-expression network was first constructed and then combined with the experimentally determined protein-protein interaction network. Proteins with statistically higher topological overlap in the integrated network were identified as common responsive proteins to both biofuels stress and environmental perturbations. In addition, a weighted gene co-expression network analysis was performed to distinguish unique responses to biofuels from those to environmental perturbations and to uncover metabolic modules and proteins uniquely associated with biofuels stress. The results showed that biofuel-specific proteins and modules were enriched in several functional categories, including photosynthesis, carbon fixation, and amino acid metabolism, which may represent potential key signatures for biofuels stress responses in Synechocystis. Network-based analysis allowed determination of the responses specifically related to biofuels stress, and the results constituted an important knowledge foundation for tolerance engineering against biofuels in Synechocystis.
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Effect of EGb761 on light-damaged retinal pigment epithelial cells.
Int J Ophthalmol
PUBLISHED: 01-01-2014
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To investigate the protective mechanism of Gingko Biloba extract (EGb761) on the ability of retinal pigment epithelial (RPE) cells to resist light-induced damage in a comparative proteomics study.
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Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-? and down-regulation of VEGFR-2 expression.
PLoS ONE
PUBLISHED: 01-01-2014
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15-lipoxygenase-1 (15-LOX-1) plays an important role in angiogenesis, but how it works still remains a controversial subject. The aims of our study are focused on determining whether or not 15-LOX-1 inhibiting oxygen-induced ischemic retinal neovascularization (RNV) and the underlying regulatory mechanism involving of 15-LOX-1, peroxisome proliferator-activated receptor ? (PPAR-?) and vascular endothelial growth factor receptor 2 (VEGFR-2) in oxygen-induced retinopathy (OIR). Recombinant adenoviral vectors that expressing the 15-LOX-1 gene (Ad-15-LOX-1-GFP) or the green fluorescence protein gene (Ad-GFP) were intravitreous injected into the OIR mice at postnatal day 12 (P12), the mice were sacrificed 5 days later (P17). Retinal 15-LOX-1 expression was significantly increased at both mRNA and protein levels after 15-LOX-1 gene transfer. Immunofluorescence staining of retinal sections revealed 15-LOX-1 expression was primarily in the outer plexiform layer (OPL), inner nuclear layer (INL) and ganglion cell layer (GCL) retina. Meanwhile, RNV was significantly inhibited indicated by fluorescein retinal angiography and quantification of the pre-retinal neovascular cells. The expression levels of PPAR-? were significantly up-regulated while VEGFR-2 were significantly down-regulated both in mRNA and protein levels. Our results suggested 15-LOX-1 gene transfer inhibited RNV in OIR mouse model via up-regulation of PPAR-? and further down-regulation of VEGFR-2 expression. This could be a potentially important regulatory mechanism involving 15-LOX-1, PPAR-? and VEGFR-2 during RNV in OIR. In conclusion, 15-LOX-1 may be a new therapeutic target for treating neovascularization diseases.
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Construction of network for protein kinases that play a role in acute pancreatitis.
Pancreas
PUBLISHED: 12-16-2013
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This study aimed to search for protein kinases that play a role in acute pancreatitis and analyze their potential connection with each other.
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[The gene mutation screening of a family with congenital fibrosis of the extraocular muscles associated with corpus callosum agenesis].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 11-22-2013
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To identify TUBB3 gene mutations in a Chinese family with congenital fibrosis of the extraocular muscle associated with corpus callosum agenesis.
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Spectral analysis of bent fiber Bragg gratings: theory and experiment.
Opt Lett
PUBLISHED: 11-02-2013
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This Letter presents a simple mathematical model developed from coupled-mode theory to describe the relationship between Bragg transmission loss (BTL), grating length, coupling coefficients, and bending loss in a bent fiber Bragg grating. In our investigation, the finding indicates that the decrement of BTL can be attributed to the increasing bending loss and degradation of both dc and ac coupling coefficients as the bending radius decreases. Besides, the center wavelength shifts as a result of coupling coefficients degradation. The validity of the proposed model is supported by experimental result.
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In vitro antifungal activity of farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida.
Ann. Clin. Microbiol. Antimicrob.
PUBLISHED: 10-30-2013
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Protein farnesylation is an important tosttranslational modification in fungi. We evaluated the antifungal activity of two farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida. Unfortunately, the MICs were vastly higher than the concentrations that inhibit the proliferation and viability of mammalian cells.
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Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage, antiproliferation and apoptotic induction activity in human cervical cancer cells.
Biometals
PUBLISHED: 09-29-2013
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Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.
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[Autophagy in lung tissue of rats exposed to silica dust].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 09-24-2013
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To investigate the autophagy of effector cells in lung tissue at different time points when rats were exposed to free SiO2 dust.
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Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways.
Mol Med Rep
PUBLISHED: 09-19-2013
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The aim of this study was to identify agents that regulate autophagy. A total of 544 differentially expressed genes were screened from the intersection set of GSE2435 and GSE31040, which was obtained from the Gene Expression Omnibus database and 19 differentially expressed kinases were selected according to a protein kinase database. Gene ontology?biological process (GO-BP) enrichment analysis revealed that the 19 kinases were mainly associated with phosphorylation. The protein-protein interaction network exhibited 30 differentially expressed genes that interacted with BRAF, and GO-BP enrichment analysis showed the function of these genes were mainly involved in cell death and apoptosis. The kinase-kinase inhibitor regulatory network identified16 kinase inhibitors that specifically inhibited BRAF. Previous studies indicated that sorafenib is capable of regulating autophagy and regorafenib has also been reported; however, there have been no studies regarding the regulation of autophagy by afatinib, selumetinib, PD318088, axitinib, TAK-733, GDC-0980, GSK2126458, PLX-4720, AS703026, trametinib, GDC-0941 and PF-04217903. Thus, these kinase inhibitors are potential targets for further study on the regulation of autophagy in the future.
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Delayed growth of glioma by a polysaccharide from Aster tataricus involve upregulation of Bax/Bcl-2 ratio, activation of caspase-3/8/9, and downregulation of the Akt.
Tumour Biol.
PUBLISHED: 09-09-2013
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In this study, a homogeneous polysaccharide (ATP-II), with a molecular weight of 3.4?×?10(4) Da, was successfully purified from Aster tataricus by DEAE-Sepharose CL-6B ion exchange and Sepharose CL-6B gel filtration chromatography. Monosaccharide component analysis indicated that ATP-II was composed of glucose, galactose, mannose, rhamnose, and arabinose in molar ratios of 2.1:5.2:2.1:1.0:1.2. We evaluated the anticancer efficacy and associated mechanisms of ATP-II on glioma C6 cells in vitro and in vivo. The results showed that treatment of C6 cells with ATP-II inhibited cell proliferation and this biological response came from induction of DAN damage and consequent inducing apoptosis. Likewise, oral ATP-II administration resulted in consistent regression of glioma tumors and induced apoptosis of transplanted tumor tissues by increasing the ratio of Bax/Bcl-2 and activation of caspase-3, caspase-8, and caspase-9 cascade. Importantly, the efficient downregulation of Akt, which is successfully detected in tumor tissues, is a unique contribution to retard the tumor growth by ATP-II. These data suggest that ATP-II may be a potential candidate for glioma treatment.
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[Prevalence and antibiogram distribution of Salmonella isolated from broiler production and processing course in four provinces, China].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 08-21-2013
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To determine the contamination condition of Salmonella in broiler breeding and slaughter processing in China and to investigate the distribution of antimicrobial resistance profiles.
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Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium.
Oncol. Rep.
PUBLISHED: 08-15-2013
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Many reports have inferred that macrophages can interact with tumor cells in the tumor microenvironment (TME) in a vicious cycle of tumor development; however, the changes in gene expression in tumor cells under the effects of macrophages are still largely unknown. The present study was carried out to illustrate the changes in the gene expression profile in lung cancer cells under the effects of macrophage-conditioned medium. Gene expression profile data were derived from the GEO database GSE9315. The GSM234968 sample was derived from a highly invasive human pulmonary adenocarcinoma cell line, CL1-5, and was treated with conditioned medium (supernatant of a culture solution of human monocyte THP-1). The GSM234967 sample that was not treated with the conditioned medium was used as a control. GO and KEGG enrichment analyses were carried out using DAVID software, and visualization networks were constructed using Cytoscape software. The results showed that 40 differentially expressed genes were annotated. Five differentially expressed transcription factors were identified, EIF2B4, EIF2B5, JUNB, GNG11 and HMGB2, which were all related to stress and responses. The gene cluster of JUNB was mainly enriched in cancer-related pathways, Wnt signaling pathway and MAPK signaling pathway. Finally, 10 small molecules, thioridazine, resveratrol, astemizole, ciclopirox, calmidazolium, etoposide, anisomycin, pyrvinium, azacyclonol and terfenadine, which may act on transcription factors, were identified using the CMap database. In conclusion, we identified transcription factors playing key roles in tumor cells under the effects of macrophages in order to provide new clues for blocking this vicious cycle of tumor development.
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Complementary iTRAQ proteomics and RNA-seq transcriptomics reveal multiple levels of regulation in response to nitrogen starvation in Synechocystis sp. PCC 6803.
Mol Biosyst
PUBLISHED: 08-15-2013
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Sequential adaptation to environmental stress needs complex regulation at different cellular levels in cyanobacteria. To uncover the regulatory mechanism in response to nitrogen starvation, we investigated the genome-wide correlation between protein abundance and gene expression in a model cyanobacterium Synechocystis sp. PCC 6803 using complementary quantitative iTRAQ proteomics and RNA-seq transcriptomics. Consistent with the cell growth inhibition, proteomic analysis indicated phase-dependent down-regulation of proteins related to nitrogen metabolism, ribosome complexes, glycolysis pathway and tricarboxylic acid (TCA) cycles by nitrogen starvation. Transcriptomic analysis also showed that genes related to "Photosynthesis", "Protein synthesis" and "Energy metabolism" were significantly down-regulated by nitrogen starvation. Interestingly, the concordance between protein abundances and their corresponding mRNAs exhibited a functional categories-dependent pattern, with some categories, such as "Protein synthesis" and "Energy metabolism", having a relatively high correlation, while others even with numerous discordant changes in protein-mRNA pairs, indicated divergent regulation of transcriptional and post-transcriptional processes. In particular, an increased abundance of proteins related to "Photosynthesis" upon nitrogen starvation was found to be reversely correlated with the down-regulation of their corresponding mRNAs. In addition, two metabolic modules highly correlated with nitrogen starvation were identified by a co-expression network analysis, and were found to contain mostly photosynthetic proteins and hypothetical proteins, respectively. We further confirmed the involvement of the photosynthetic genes in nitrogen starvation tolerance by constructing and analyzing the psbV gene deletion mutant.
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Orientation-dependant inclinometer based on intermodal coupling of two-LP-modes in a polarization-maintaining photonic crystal fiber.
Opt Express
PUBLISHED: 08-14-2013
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A reflective optic-fiber orientation-dependant inclinometer, in which a short piece of polarization-maintaining photonic crystal fiber (PM-PCF) is spliced with a lead-in single mode fiber (SMF) without any offset, is proposed and experimentally demonstrated. The hollow holes within the PM-PCF are partly collapsed due to the directional arc-heating splicing and couple two linearly polarized (LP) modes into the downstream PM-PCF. Then two LP-modes are reflected at the end face of PM-PCF and recoupled back into the lead-in SMF again via the collapsed splicing cross section. A well-defined interference pattern is obtained as the result of polarized modes interference. Both orientation and sensitivity of bending is determined unambiguously with this compact PM-PCF configuration.
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Draft Genome Sequence of Lactococcus lactis subsp. lactis Strain YF11.
Genome Announc
PUBLISHED: 08-10-2013
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Lactococcus lactis subsp. lactis strain YF11 is a food preservative bacterium with a high capacity to produce nisin. Here, we announce the draft genome sequence of Lactococcus lactis subsp. lactis YF11 (2,527,433 bp with a G+C content of 34.81%).
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Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway.
Oxid Med Cell Longev
PUBLISHED: 08-09-2013
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In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway.
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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.