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Find video protocols related to scientific articles indexed in Pubmed.
Benzalkonium Chloride induces Subconjunctival Fibrosis through the COX-2- modulated activation of a TGF-?1/Smad3 Signaling Pathway.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-20-2014
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Purpose. The purpose is to investigate the mechanism of subconjunctival fibrosis caused by benzalkonium chloride (BAC), which is the most common preservative in ophthalmic preparations. Methods. The left eyes of male Sprague-Dawley rats were topically treated with 0.01% BAC or phosphate buffered saline (PBS) twice daily for one month. Primary conjunctival fibroblasts (CFs) were exposed for 24 hours to 0.00005% BAC, 0.000075% BAC, 0.000075% BAC+LY2157299 (a selective transforming growth factor ? receptor type I inhibitor), 0.000075% BAC+NS-398 (a selective cyclooxygenase-2 inhibitor) and PBS, respectively. The pathological changes of the bulbar conjunctival tissue of rats were examined using haematoxylin-eosin (HE), Van Gieson's (vG), periodic acid-Schiff (PAS) stains, or immunohistochemisty (IHC). The expression of the extracellular matrix (ECM), the transforming growth factor ? (TGF-?) signaling pathway-related molecules, and cyclooxygenase-2 (COX-2) in bulbar conjunctival tissues and CFs were detected using western blot (WB) and quantitative real-time RT-PCR (qRT-PCR). Results. Rats treated with 0.01% BAC exhibited a slight increase of the fibroblast density and a more compact collagen deposition in the bulbar subepithelial connective tissues in comparison with rats treated with PBS. WB and qRT-PCR analyses showed that the expression of ECM, TGF-? signaling pathway-related molecules, and COX-2 were markedly increased in the bulbar conjunctival tissues of rats exposed to 0.01% BAC and in CFs exposed to 0.00005% and 0.000075% BAC. In CFs, BAC-induced ECM expression was clearly decreased by LY2157299, while the BAC-induced activation of the TGF-?1/Smad3 signaling pathway was greatly attenuated by NS-398. Conclusion. BAC-induced subconjunctival fibrosis is a consequence of excessive ECM production of CFs through the COX-2-modulated activation of a TGF-?1/Smad3 Signaling Pathway.
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MicroRNA-200 Cluster Regulation by Ascl2: Impact on the Epithelial-mesenchymal Transition in Colon Cancer Cells.
J. Biol. Chem.
PUBLISHED: 11-06-2014
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Achaete scute-like 2 (Ascl2), a basic helix-loop-helix (bHLH) transcription factor, is a downstream target of Wnt signaling that controls the fate of intestinal cryptic stem cells and colon cancer progenitor cells. However, its involvement in colon cancer and downstream molecular events is largely undefined; in particular, the mechanism by which Ascl2 regulates the plasticity of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) programs in colon cancer cells remains unknown. In this study, we systematically demonstrate that Ascl2 loss-of-function in colon cancer cells promotes MET by de-repressing the expression of miR-200s (i.e., miR-200b, miR-200a, miR-429, miR-200c and miR-141) and further activating their expression through a transcriptional mechanism that involves direct binding to the most proximal E-box (E-box2) in the miR-200b-a-429 promoter. Activation of miR-200s due to Ascl2 deficiency led to the inhibition of Zeb1/2 expression and the alteration of epithelial and mesenchymal features. Transfection of miR-200b, miR-200a and miR-429 inhibitors into Ascl2-deficient colon cancer cells promoted the epithelial-mesenchymal transition in a reversible manner. Transfection of miR-200a or miR-429 inhibitors into Ascl2-deficient colon cancer cells increased cellular proliferation and migration. Ascl2 mRNA levels and miRNA-200a, miRNA-200b, miRNA-200c, miRNA-141 or miRNA-429 levels in the colon cancerous samples were inversely correlated. These results provide the first evidence of a link between Ascl2 and miR-200s in the regulation of EMT-MET plasticity in colon cancer.
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High-Sensitivity Troponin T and Cardiovascular Events in Systolic Blood Pressure Categories: Atherosclerosis Risk in Communities Study.
Hypertension
PUBLISHED: 10-29-2014
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Based on observational studies, there is a linear increase in cardiovascular risk with higher systolic blood pressure (SBP), yet clinical trials have not shown benefit across all SBP categories. We assessed whether troponin T measured using high-sensitivity assay was associated with cardiovascular disease within SBP categories in 11?191 Atherosclerosis Risk in Communities study participants. Rested sitting SBP by 10-mm?Hg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease, and stroke were ascertained for a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with SBP<140 mm?Hg and troponin T ?3 ng/L. Higher troponin T was associated with increasing cardiovascular events across most SBP categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of SBP with cardiovascular events across troponin T categories. Individuals with troponin T ?3 ng/L and SBP <140 mm?Hg had higher cardiovascular risk compared with those with troponin T <3 ng/L and SBP 140 to 159 mm?Hg. Higher troponin T levels within narrow SBP categories portend increased cardiovascular risk, particularly for heart failure. Individuals with lower SBP but measurable troponin T had greater cardiovascular risk compared with those with suboptimal SBP but undetectable troponin T. Future trials of systolic hypertension may benefit by using high-sensitivity troponin T to target high-risk patients.
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[Long term follow-up and prognostic analysis of 85 cases with primary gastrointestinal diffuse large B cell lymphoma].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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To analyze the clinical characteristics, prognostic factors in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL).
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Spatio-temporal distribution of phenolamides and the genetics of natural variation of hydroxycinnamoyl spermidine in rice.
Mol Plant
PUBLISHED: 10-01-2014
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Phenolamides constitute a diverse class of secondary metabolites that are found ubiquitously in plants and have been implicated to play important role in a wide range of biological processes such as plant development and defense. However, spatio-temporal accumulation patterns of phenolamides in rice, one of the most important crops, are not available so far, and no gene responsible for the phenolamides biosynthesis has been identified in this species. In this report, we report here the comprehensive metabolic profiling and natural variation analysis of phenolamides in a collection of rice germplasm using an LC-MS-based targeted metabolomics method. Spatio-temporal controlled accumulations were observed for most phenolamides, together with their differential accumulations between the two major subspecies of rice. Further metabolic genome-wide association study (mGWAS) in rice leaf and the in vivo metabolic analysis of the transgenic plants identified Os12g27200 and Os12g27254 as two spermidine hydroxycinnamoyl transferases that might be underlying the natural variation of levels of spermidine conjugates in rice. Our work demonstrates 'gene-to-metabolite' analysis by mGWAS provides a useful tool for functional gene identification and omics-based crop genetic improvement.
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HMGB1 promotes cellular proliferation and invasion, suppresses cellular apoptosis in osteosarcoma.
Tumour Biol.
PUBLISHED: 08-29-2014
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Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the deregulation of DNA-binding protein high-mobility group box 1 (HMGB1) was associated with the development of cancer. This study aimed to explore the expression of HMGB1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the role of HMGB1 in the development of osteosarcoma. The results from RT-PCR and Western blot showed that the expression rate of HMGB1 messenger RNA (mRNA) and the expression of HMGB1 in the osteosarcoma tissues were significantly higher than those in normal bone tissue (p?
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[The clinical characteristics of polyserositis as main presentation of chronic graft-versus-host rejection disease after allogeneic hematopoietic stem cell transplantation].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 08-23-2014
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To analyze the clinical characteristics of polyserositis associated with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic transplantation(allo-HSCT).
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Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9.
RNA Biol
PUBLISHED: 08-19-2014
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Recent genome-wide studies have revealed that the majority of the mouse genome is transcribed as non-coding RNAs (ncRNAs) and growing evidence supports the importance of ncRNAs in regulating gene expression and epigenetic processes. However, the low efficiency of conventional gene targeting strategies has hindered the functional study of ncRNAs in vivo, particularly in generating large fragment deletions of long non-coding RNAs (lncRNAs) with multiple expression variants. The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has recently been applied as an efficient tool for engineering site-specific mutations of protein-coding genes in the genome. In this study, we explored the potential of using the CRISPR/Cas9 system to generate large genomic deletions of lncRNAs in mice. We developed an efficient one-step strategy to target the maternally expressed lncRNA, Rian, on chromosome 12 in mice. We showed that paired sgRNAs can precisely generate large deletions up to 23kb and the deletion efficiency can be further improved up to 33% by combining multiple sgRNAs. The deletion successfully abolished the expression of Rian from the maternally inherited allele, validating the biological relevance of the mutations in studying an imprinted locus. Mutation of Rian has differential effects on expression of nearby genes in different somatic tissues. Taken together, we have established a robust one-step method to engineer large deletions to knockout lncRNA genes with the CRISPR/Cas9 system. Our work will facilitate future functional studies of other lncRNAs in vivo.
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BEVACIZUMAB VERSUS RANIBIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Meta-analysis of Randomized Controlled Trials.
Retina (Philadelphia, Pa.)
PUBLISHED: 08-07-2014
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To evaluate the relative efficacy and safety of bevacizumab versus ranibizumab for the treatment of the neovascular form of age-related macular degeneration.
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(+)-Catechin ameliorates diabetic nephropathy by trapping methylglyoxal in type 2 diabetic mice.
Mol Nutr Food Res
PUBLISHED: 08-01-2014
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Accumulation of glycolytic metabolite methylglyoxal (MG) in diabetic kidney is thought to contribute to the pathogenesis of nephropathy, either as a direct toxin or as a precursor for advanced glycation end products (AGEs). Using (+)-catechin (CE), a novel MG trapper, we investigated whether MG trapping is sufficient to prevent the progression of diabetic nephropathy in type 2 diabetic mice.
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A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.
Med. Sci. Monit.
PUBLISHED: 07-29-2014
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The aim of this study was to investigate the possible correlation between levels of serum liver enzymes and impaired fasting glucose (IFG) in Chinese adults and to provide a new perspective for the prevention of pre-diabetes.
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Yellow-light generation and engineering in zinc-doped cadmium sulfide nanobelts with low-threshold two-photon excitation.
Nanotechnology
PUBLISHED: 07-23-2014
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Through a simple doping route with zinc ion as a dopant in cadmium sulfide nanobelts, a bright yellow-colored light was obtained. The detailed chromaticity and brightness of the light can be engineered by the dopant concentration and the pumping power, which are used to control the dominant wavelength to any fine yellow color, and even cover the sodium-yellow-line of 589 nm. The nanobelts were synthesized through a chemical vapor deposition method. The peak shift of the XRD result proves that the zinc ions as a dopant exist in the nanobelts rather than in the ZnCdS alloy formation. Time-resolved photoluminescence of the nanobelt reveals the existence of the defect-related state, which induces a red band to further mix with green band-edge emission to form the yellow light. Moreover, low-threshold two-photon excitation was observed in the proper Zn-doped cadmium sulfide nanobelts. The dopant and pumping power-tuned generation and engineering of the yellow light makes it possible to use this kind of material as yellow light-emitting source.
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Inhibition of TNF-? in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats.
Toxicol. Appl. Pharmacol.
PUBLISHED: 07-12-2014
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We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-?) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-?B (NF-?B) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-? blocker (pentoxifylline or etanercept) or vehicle for 4weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (?-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-?B p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-? in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-?B p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy.
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Multi-faced neuroprotective effects of geniposide depending on the RAGE-mediated signaling in an Alzheimer mouse model.
Neuropharmacology
PUBLISHED: 07-03-2014
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The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to A?-induced pathogenic responses. Geniposide, a pharmacologically active component purified from gardenia fruit, could attenuate the oligomeric A?1-42-induced inflammatory response by blocking the ligation of A? to RAGE and suppressing the RAGE-mediated signaling in vitro. Here, we investigated whether geniposide can exert protective effects on the neuroinflammation and memory deficits in an Alzheimer's disease (AD) mouse model. The results indicate that geniposide treatment significantly suppresses RAGE-dependent signaling (activation of ERK and I?B/NF-?B), the production of tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) and cerebral A? accumulation in vivo. Furthermore, we demonstrate that geniposide augments synaptic plasticity by attenuating the A?-induced reduction of long-term potentiation and increasing the miniature excitatory postsynaptic current (mEPSC) amplitude and frequency in hippocampal neurons. In addition, the intragastric administration of geniposide improves learning and memory in APP/PS1 mice. Taken together, these studies indicate that geniposide has profound multifaceted neuroprotective effects in an AD mouse model. Geniposide demonstrates its neuroprotection by inhibiting inflammation, ameliorating amyloid pathology and improving cognition. Thus, geniposide may be a potential therapeutic agent for halting and preventing AD progression.
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Real-time 3D particle manipulation visualized using volume holographic gratings.
Opt Lett
PUBLISHED: 07-01-2014
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Holographic optical tweezers (HOTs) extend optical trapping into three dimensions. Volume imaging then becomes a concern as trapped objects are easily moved out of focus of the imaging objective lens. Here we demonstrate a three-dimensional real-time interactive optical trapping, manipulating, and imaging system based on HOTs incorporated with volume holographic microscope. Intensity information about the trapped objects at multiple depths can be captured in a single measurement. This method is compatible with most imaging modes such as bright-field and fluorescence.
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The complete mitochondrial genome of Paecilomyces hepiali (Ascomycota, Eurotiomycetes).
Mitochondrial DNA
PUBLISHED: 06-26-2014
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Abtract Paecilomyces hepiali, belonging to the Eurotiales order Ascomycota, is an endoparasitic fungus that commonly exists in the natural Cordyceps sinensis anamorph stage. Here, we report the complete mitochondrial DNA sequences of P. hepiali for the first time. The genome is 24,245?bp in length, encoding 15 protein-coding genes (PCGs), 2 rRNA genes, 25 tRNA genes and 3 homing endonucleases. The overall AT composition is 73.37% and the average AT content of PCG, rRNA, tRNA and non-coding region are 74.21%, 66.07%, 62.83% and 75.96%, respectively. Phylogenetic analysis with eight Ascomycota species and thirteen Basidiomycota species revealed that P. hepiali is was more closely related to Cordyceps bassiana, Cordycep smilitaris and Cordyceps brongniartii. It is confirmed that P. hepiali is a derivative of Cordyceps sinensis. This study provided valuable information on the gene contents of the mitochondrial genome and would facilitate the study of function and evolution of P. hepiali.
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Notoginsenoside R1 increases neuronal excitability and ameliorates synaptic and memory dysfunction following amyloid elevation.
Sci Rep
PUBLISHED: 06-23-2014
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Neurodegeneration and synaptic dysfunction observed in Alzheimer's disease (AD) have been associated with progressive decrease in neuronal activity. Here, we investigated the effects of Notoginsenoside R1 (NTR1), a major saponin isolated from Panax notoginseng, on neuronal excitability and assessed the beneficial effects of NTR1 on synaptic and memory deficits under the A?-enriched conditions in vivo and in vitro. We assessed the effects of NTR1 on neuronal excitability, membrane ion channel activity, and synaptic plasticity in acute hippocampal slices by combining electrophysiological extracellular and intracellular recording techniques. We found that NTR1 increased the membrane excitability of CA1 pyramidal neurons in hippocampal slices by lowering the spike threshold possibly through a mechanism involving in the inhibition of voltage-gated K(+) currents. In addition, NTR1 reversed A?1-42 oligomers-induced impairments in long term potentiation (LTP). Reducing spontaneous firing activity with 10 nM tetrodotoxin (TTX) abolished the protective effect of NTR1 against A?-induced LTP impairment. Finally, oral administration of NTR1 improved the learning performance of the APP/PS1 mouse model of AD. Our work reveals a novel mechanism involving in modulation of cell strength, which contributes to the protective effects of NTR1 against A? neurotoxicity.
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[Toxicity research status of benzalkonium chloride on ocular surface].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 06-17-2014
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Benzalkonium chloride (BAC) is the most commonly used preservative in ophthalmic preparations.So far large bodies of clinical and experimental studies have shown that use of topical drugs containing BAC can induce a series of ocular surface diseases, such as apoptosis.However, recently, some clinical studies have shown that ocular toxicity in patients treated with eye drops containing BAC has not apparent correlated with BAC.Some scholars consider that the limitations of the research lead people to recognize the BAC toxicity exaggeratedly.Here we summarize numerous clinical and experimental studies of BAC in the past few years, and focus on reviewing recent researches of the toxic effect of BAC on ocular surface.
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Combined Use of a Gasket Seal Closure and a Vascularized Pedicle Nasoseptal Flap Multilayered Reconstruction Technique for High-Flow Cerebrospinal Fluid Leaks After Endonasal Endoscopic Skull Base Surgery.
World Neurosurg
PUBLISHED: 06-03-2014
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To assess the efficacy of the combined use of a gasket seal closure and a vascularized pedicle nasoseptal flap (VP-NSF) multilayered reconstruction technique for high-flow cerebrospinal fluid (CSF) leaks resulting from endonasal endoscopic skull base surgery.
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Altered Brain White Matter Integrity in Temporal Lobe Epilepsy: A TBSS Study.
J Neuroimaging
PUBLISHED: 05-26-2014
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The aim of this study is to explore the possible changed cerebral white matter regions in patients with temporal lobe epilepsy (TLE) using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS).
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Anatomical study of suboccipital vertebral arteries and surrounding bony structures using virtual reality technology.
Med. Sci. Monit.
PUBLISHED: 05-16-2014
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This work aimed to evaluate the efficacy of virtual reality (VR) technology in neurosurgical anatomy through a comparison of the virtual 3D microanatomy of the suboccipital vertebral arteries and their bony structures as part of the resection of tumors in the craniovertebral junction (CVJ) of 20 patients compared to the actual microanatomy of the vertebral arteries of 15 cadaveric headsets.
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Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo.
Mol. Cancer Ther.
PUBLISHED: 05-05-2014
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Although silybin, a natural flavonolignan, has been shown to exhibit potent antitumor activities against various types of cancers, including lung cancer, the molecular mechanisms behind these activities remain unclear. Silent information regulator 1 (SIRT1) is a conserved NAD(+)-dependent deacetylase that has been implicated in the modulation of transcriptional silencing and cell survival. Furthermore, it plays a key role in carcinogenesis through the deacetylation of important regulatory proteins, including p53. In this study, we investigated the antitumor activity of silybin towards human lung adenocarcinoma cells in vitro and in vivo and explored the role of the SIRT1 signaling pathway in this process. Silybin treatment resulted in a dose- and time-dependent decrease in lung adenocarcinoma A549 cell viability. In addition, silybin exhibited strong antitumor activity illustrated by reductions in tumor cell adhesion, migratory capability, and glutathione levels and by increased apoptotic indices and reactive oxygen species levels. Silybin treatment also downregulated SIRT1 and upregulated p53 acetylation. SIRT1 siRNA (in vitro) or cambinol (a known SIRT1 inhibitor used for in vivo studies) further enhanced the antitumor activity of silybin. In summary, silybin is a potent inhibitor of lung adenocarcinoma cell growth that interferes with SIRT1 signaling, and this inhibition is a novel mechanism of silybin action that may be used for therapeutic intervention in lung adenocarcinoma treatment.
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Geniposide attenuates mitochondrial dysfunction and memory deficits in APP/PS1 transgenic mice.
Curr Alzheimer Res
PUBLISHED: 04-23-2014
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Oxidative stress and mitochondrial dysfunction appear early and contribute to the disease progression in Alzheimer's disease (AD), which can be detected extensively in AD patients brains as well as in transgenic AD mice brains. Thus, treatments that result in attenuation of oxidative stress and mitochondrial dysfunction may hold potential for AD treatment. Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits anti-oxidative, antiinflammatory and other important therapeutic properties. However, whether geniposide has any protective effect on oxidative stress and mitochondrial dysfunction in AD transgenic mouse model has not yet been reported. Here, we demonstrate that intragastric administration of geniposide significantly reduces oxidative stress and mitochondrial dysfunction in addition to improving learning and memory in APP/PS1 mice. Geniposide exerts protective effects on mitochondrial dysfunction in APP/PS1 mice through suppressing the mitochondrial oxidative damage and increasing the mitochondrial membrane potential and activity of cytochrome c oxidase. These studies indicate that geniposide may attenuate memory deficits through the suppression of mitochondrial oxidative stress. Thus, geniposide may be a potential therapeutic reagent for halting and preventing AD progress.
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Geniposide attenuates oligomeric A?(1-42)-induced inflammatory response by targeting RAGE-dependent signaling in BV2 cells.
Curr Alzheimer Res
PUBLISHED: 04-20-2014
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The neuroinflammation induced by amyloid-? (A?) is one of the key events in Alzheimer's disease (AD) progress in which microglia are the main cells involved. Receptor for advanced glycation end products (RAGE) mediates and enhances A?-induced microglial activation and leads to induction of proinflammatory mediators, such as tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?). Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits a broad spectrum anti-inflammatory effect as well as neurotrophic and neuroprotective properties. However, the effects of geniposide on A?-mediated microglial pathways have not been fully discovered. Here, we demonstrate that geniposide treatment significantly blocks A?-induced RAGE-dependent signaling (activation of ERK and NF-?B) along with the production of TNF-? and IL-1? in cultured BV2 microglia cells. Notably, based on the data from coimmunoprecipitation assay, we infer that geniposide exerts protective effects on A?-induced inflammatroy response through blocking A? binding to RAGE and suppressing the RAGE-mediated signaling pathway. Taken together, these findings indicate that geniposide is a potent suppressor of neuroflammation through inhibiting RAGE-dependent signaling pathway. Thus, geniposide may be a potential therapeutic agent for the treatment of neuroinflammation that is involved in neurological diseases such as AD.
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Emulsified isoflurane enhances thermal transient receptor potential vanilloid-1 channel activation-mediated sensory/nociceptive blockade by QX-314.
Anesthesiology
PUBLISHED: 03-27-2014
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QX-314 produces nociceptive blockade, facilitated by permeation through transient receptor potential vanilloid-1 (TRPV1) channels. TRPV1 channel can be activated by noxious heat and sensitized by volatile anesthetics. The authors hypothesized that emulsified isoflurane (EI) could enhance thermal TRPV1 channel activation-mediated sensory/nociceptive blockade by QX-314.
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Cloning, expression, and ligand-binding characterization of two neuropeptide Y receptor subtypes in orange-spotted grouper, Epinephelus coioides.
Fish Physiol. Biochem.
PUBLISHED: 03-15-2014
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As one of the most important multifunctional peptides, neuropeptide Y (NPY) performs its physiological functions through different subtype receptors. In this study, full-length cDNAs of two NPY receptors (YRs) in orange-spotted grouper (Epinephelus coioides) were cloned and named npy8br (y8b) and npy2r (y2). Phylogenetic analysis indicated that the Y8b receptor is an ortholog of the teleostean Y8b receptor, which belongs to the Y1 subfamily, and the Y2 receptor is an ortholog of the teleostean Y2 receptor, which belongs to the Y2 subfamily. Both of the YRs have G protein-coupled receptor family profiles. Multiple alignments demonstrate that the extracellular loop regions of YRs have distinctive residues of each species. Expression profile analysis revealed that the grouper Y8b receptor mRNA is primarily expressed in the brain, stomach and intestine, while the grouper Y2 receptor mRNA is primarily expressed in the brain, ovary, liver and heart. Double immunofluorescence analysis determined that the grouper YRs interact with the grouper NPY around the human embryonic kidney 293T cell surface. Furthermore, site-directed mutagenesis in a phage display system revealed that Asp(6.59) might be a common NPY-binding site, while Asp(2.68) of the Y8b receptor and Glu(5.24) of the Y2 receptor could be likely involved in subtype-specific binding. Combining the expression profile and ligand-binding feature, the grouper Y8b receptor could be involved in regulating food intake via the brain-gut axis and the grouper Y2 receptor might play a role in balancing the regulatory activity of the Y8b receptor and participate in metabolism in the liver and ovary.
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Lymphomatoid papulosis misdiagnosed as pityriasis lichenoides et varioliformis acuta: Two case reports and a literature review.
Exp Ther Med
PUBLISHED: 03-01-2014
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The aim of this study was to improve the level of diagnosis and differential diagnosis of lymphomatoid papulosis (LyP). Two cases of type B LyP were identified and the literature was reviewed to summarize the clinical outcomes and pathology of LyP and its treatment. The two patients exhibited symptoms with papulonodular lesions, the centers of which gradually underwent ulceration and necrosis. CD30, a helper T-cell marker specifically expressed in tumor cells was analyzed by immunohistochemical staining and the result showed that CD30-negative or only scattered CD30-positive cells were present. Therefore, a diagnosis of type B LyP was made. A fairly good curative effect was achieved following treatment with retinoic acid, glucocorticoids and immunomodulatory drugs. LyP is a type of low-level malignant lymphoma and is easily misdiagnosed as pityriasis lichenoides et varioliformis acuta and other diseases. In order to avoid under diagnosis and misdiagnosis, doctors should evaluate suspected patients by histopathological and immunohistochemical examination.
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Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 02-20-2014
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To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants.
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Extranodal natural killer/T-cell lymphoma, nasal type, involving the skin, misdiagnosed as nasosinusitis and a fungal infection: A case report and literature review.
Oncol Lett
PUBLISHED: 02-14-2014
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The present study reports a case of extranodal natural killer (NK)/T-cell lymphoma, nasal type, involving the skin. The clinical manifestations, pathological characteristics, treatment and prognosis of the case were analyzed to improve the clinical diagnosis and treatment for this disease. The patient was a 56-year-old male, presenting with dark red nodules and plaques that had been visible on the nose for half a year. Based on the skin lesions and histopathological and immunohistochemical examination results, the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. This disease has unique histopathological and immunohistochemical features and a high malignancy. The condition tends to be misdiagnosed and has a poor prognosis, but seldom involves the skin. In the present case, only radiotherapy was performed, with no relapse occurring within 6 months.
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Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay.
J. Am. Coll. Cardiol.
PUBLISHED: 02-12-2014
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The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts.
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Non-essential amino acids attenuate apoptosis of gastric cancer cells induced by glucose starvation.
Oncol. Rep.
PUBLISHED: 02-06-2014
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Energy and nutrition are essential requirements for all living cells, including cancer cells. In the initiating stage of cancer in organs, cancer cells grow fast and have inadequate supplies of glucose, oxygen and other nutrients due to deficient angiogenesis. Anaerobic conditions cause cancer cells to rely on glycolysis, which produces pyruvate and ATP that can be used by cancer cells to survive. However, glucose starvation may result in apoptosis or necrosis of cancer cells. It has been reported that autophagy is a consequence of glucose starvation and that amino acids are products of autophagy. The present study investigated whether amino acids may represent an alternative energy source for cancer cells undergoing glucose starvation. With non-essential amino acids, growth inhibition and apoptosis of gastric cancer cells induced by glucose starvation were attenuated compared with that of cells undergoing glucose starvation without amino acids, as measured by cell viability, apoptosis rates, membrane potential of mitochondria, and apoptosis-related genes. Meanwhile, both mitochondrial DNA copy number and amino acid transporter genes were increased compared with those in control cells. Non-essential amino acids prevented gastric cancer cells from glucose starvation-induced apoptosis.
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Mitogen-activated protein kinase pathway is pivotal for anoikis resistance in metastatic hepatoma cells.
Mol Med Rep
PUBLISHED: 01-29-2014
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It is important for metastatic cancer cells to acquire anoikis resistance for survival in the circulatory system. In the present study, metastatic hepatoma cells were demonstrated to acquire anoikis resistance, which renders them more invasive, more resistant to anticancer agents and able to evade the host immune system for long?term survival. One of the most significant characteristics of these anoikis?resistant metastatic hepatoma cells is their proliferation inhibition. However, when microarray results were analyzed to identify the underlying molecular mechanism, the mitogen?activated protein kinase (MAPK) signaling pathway was found to be markedly upregulated, which appeared to conflict with the proliferation inhibition state. To investigate this result and the associated mechanism, protein kinase inhibitors were used to inhibit the phosphatidylinositol 3?kinase (PI-3K)/AKT and MAPK pathways. It was found that anoikis-resistant hepatoma cells may compensate for the inhibition of PI-3K/AKT or MAPK pathways by cross-talk between these two pathways, which increases their survival capacity during metastasis. In concordance with this result, western blot analysis revealed that the phosphorylation level of extracellular signal?related kinase protein was increased when the PI-3K/AKT pathway was inhibited. Therefore, it was concluded that when metastatic hepatoma cells aggregate in blood vessels, proliferation is inhibited and the MAPK signaling pathway is upregulated, which increases the long?term survival of the cells. Furthermore, a compensatory interplay between the AKT and MAPK signaling pathways was observed in the present study. Using kinase inhibitors for the two pathways in combination may yield a substantial advance in successfully producing a downstream phenotypic response in anoikis?resistant metastatic hepatoma cells.
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Dual sgRNAs facilitate CRISPR/Cas9-mediated mouse genome targeting.
FEBS J.
PUBLISHED: 01-29-2014
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The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system is a versatile RNA-guided mammalian genome modification system. One-step generation of mouse genome targeting has been achieved by co-microinjection of one-cell stage embryos with Cas9 mRNA and small/single guide (sg)RNA. Many studies have focused on enhancing the efficiency of this system. In the present study, we report that simultaneous use of dual sgRNAs to target an individual gene significantly improved the Cas9-mediated genome targeting with a bi-allelic modification efficiency of up to 78%. We further observed that the target gene modifications were characterized by efficient germline transmission and site-dependent off-target effects, and also that the apolipoprotein E gene knockout-mediated defects in blood biochemical parameters were recapitulated by CRISPR/Cas9-mediated heritable gene modification. Our results provide a dual sgRNAs strategy to facilitate CRISPR/Cas9-mediated mouse genome targeting.
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Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects.
Nat. Methods
PUBLISHED: 01-24-2014
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Bacterial RNA-directed Cas9 endonuclease is a versatile tool for site-specific genome modification in eukaryotes. Co-microinjection of mouse embryos with Cas9 mRNA and single guide RNAs induces on-target and off-target mutations that are transmissible to offspring. However, Cas9 nickase can be used to efficiently mutate genes without detectable damage at known off-target sites. This method is applicable for genome editing of any model organism and minimizes confounding problems of off-target mutations.
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Neuropeptide B in Nile tilapia Oreochromis niloticus: molecular cloning and its effects on the regulation of food intake and mRNA expression of growth hormone and prolactin.
Gen. Comp. Endocrinol.
PUBLISHED: 01-24-2014
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Neuropeptide B (NPB) regulates food intake, energy homeostasis and hormone secretion in mammals via two G-protein coupled receptors, termed as GPR 7 and GPR 8. However, there is no study that reports the function of NPB in teleosts. In this study, the full-length cDNA of prepro-NPB with the size of 663bp was cloned from the hypothalamus of Nile tilapia. The CDS of the prepro-NPB is 387bp which encodes a precursor protein with the size of 128a.a. This precursor contains a mature peptide with the size of 29a.a, and it was named as NPB29. Tissue distribution study showed that this gene was mainly expressed in different parts of brain, especially in the diencephalon as well as hypothalamus, and the spinal cord in Nile tilapia. Fasting significantly stimulated the mRNA expression of NPB in the brain area without hypothalamus, and refeeding after fasting for 3 and 14days also showed similar effects on NPB expression. While, only short-term fasting (3days) and refeeding after fasting for 7 and 14days induced mRNA expression of NPB in the hypothalamus. Intraperitoneal (i.p.) injection of NPB remarkably elevated the mRNA expression of hypothalamic neuropeptide Y (NPY), cholecystokinin 1 (CCK1) and pituitary prolactin (PRL), whereas significantly inhibited growth hormone (GH) expression in pituitary. These observations in the present study suggested that NPB may participate in the regulation of feeding and gene expression of pituitary GH and PRL in Nile tilapia.
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Emulsified isoflurane increases convulsive thresholds of lidocaine and produces neural protection after convulsion in rats.
Anesth. Analg.
PUBLISHED: 01-22-2014
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Local anesthetic-induced convulsions remain a concern of anesthesiologists when performing regional anesthesia. Our previous study found that the lidocaine requirement for IV regional anesthesia was reduced with coadministration of emulsified isoflurane. We designed this study to examine whether emulsified isoflurane could increase the convulsive threshold of lidocaine and produce protection after a lidocaine-induced convulsion.
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Cantharidin induces G2/M phase arrest and apoptosis in human gastric cancer SGC-7901 and BGC-823 cells.
Oncol Lett
PUBLISHED: 01-14-2014
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The aim of the present study was to investigate the effect of cantharidin (CTD) on human gastric cancer cells and to explore the underlying mechanisms of these effects. The human gastric cancer SGC-7901 and BGC-823 cell lines were treated with CTD. MTS assays were then employed to examine cellular proliferation, flow cytometry was used to analyze the cell cycle and apoptosis, and western blot analysis was used to determine protein expression levels. It was found that CTD inhibited the proliferation of the human gastric cancer SGC-7901 and BGC-823 cells in a dose- and time-dependent manner in vitro. CTD also induced G2/M phase arrest and cellular apoptosis in a dose-dependent manner. In addition, CTD increased the levels of p21, caspase-7, -8 and -9, activated caspase-3, poly ADP ribose polymerase and Bad, but decreased the levels of cyclin-dependent kinase 1, cyclin A and B, B-cell lymphoma-2 (Bcl-2) and Bid. The present results suggested that CTD may inhibit the proliferation of human gastric cancer SGC-7901 and BGC-823 cells in vitro by inducing G2/M phase arrest and cell apoptosis. CTD may induce cellular G2/M phase arrest by regulating cycle-associated proteins and induce apoptosis by activating a caspase cascade or regulating the Bcl-2 family proteins.
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An in situ repositioning bone flap in retrosigmoid craniotomy for cranial reconstruction.
J Craniofac Surg
PUBLISHED: 01-11-2014
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Osteoplastic craniotomy in retrosigmoid approaches to the cerebellopontine angle region has been suggested as an alternative to traditional osteoclastic craniectomy. It is important both for prevention of postoperative complications and for cosmetic purposes. The authors investigated a safe and effective method of cranial reconstruction by repositioning a 1-step formed bone flap without bone window extension in lateral suboccipital craniotomy.
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Orange-spotted grouper (Epinephelus coioides) adiponectin receptors: molecular characterization, mRNA expression, and subcellular location.
Gen. Comp. Endocrinol.
PUBLISHED: 01-07-2014
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Adiponectin is an abundantly secreted adipokine from adipose tissue in mammals, which plays important roles in the regulation of glucose and lipid metabolism. The biological function of adiponectin is mediated by at least two receptors (AdipoR1 and AdipoR2). Although both of them were identified in mammals, there are few researches about adiponectin and its receptors in teleosts. In this study, two types of adiponectin receptors have been isolated and characterized in the orange-spotted grouper (Epinephelus coioides). The cDNAs of grouper AdipoR1 and AdipoR2 are 1444 and 2034 bp in length, encoding proteins of 376 amino acids and 375 amino acids, respectively. Multiple alignment results showed that there was a variable region at the N-terminal of AdipoR1/R2, which has never been reported. Both AdipoR1 and AdipoR2 were found to be widely expressed in various tissues of grouper. Compared to AdipoR2, AdipoR1 expressed at higher levels in the nervous system and pituitary gland, but at lower levels in some peripheral tissues, including heart, liver, adipose tissue, stomach, intestine and especially gonad. Fasting and refeeding experiments showed that the mRNA expressions of AdipoR1/R2 were up-regulated by fasting in the muscle and adipose tissue of grouper, and restored rapidly to normal levels after refeeding. However, the mRNA expressions of AdipoR1/R2 in the hypothalamus and liver of grouper were insensitive to fasting. By indirect immunofluorescence, we demonstrated that grouper AdipoR1/R2 were integral membrane proteins; the C-terminals were extracellular, while the N-terminals were intracellular.
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Transcatheter versus surgical closure of perimembranous ventricular septal defects in children: a randomized controlled trial.
J. Am. Coll. Cardiol.
PUBLISHED: 01-06-2014
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The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial.
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Decision tree analysis of traditional risk factors of carotid atherosclerosis and a cutpoint-based prevention strategy.
PLoS ONE
PUBLISHED: 01-01-2014
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Reducing the exposure to risk factors for the prevention of cardio-cerebral vascular disease is a crucial issue. Few reports have described practical interventions for preventing cardiovascular disease in different genders and age groups, particularly detailed and specific cutpoint-based prevention strategies.
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Somatic mutations favorable to patient survival are predominant in ovarian carcinomas.
PLoS ONE
PUBLISHED: 01-01-2014
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Somatic mutation accumulation is a major cause of abnormal cell growth. However, some mutations in cancer cells may be deleterious to the survival and proliferation of the cancer cells, thus offering a protective effect to the patients. We investigated this hypothesis via a unique analysis of the clinical and somatic mutation datasets of ovarian carcinomas published by the Cancer Genome Atlas. We defined and screened 562 macro mutation signatures (MMSs) for their associations with the overall survival of 320 ovarian cancer patients. Each MMS measures the number of mutations present on the member genes (except for TP53) covered by a specific Gene Ontology (GO) term in each tumor. We found that somatic mutations favorable to the patient survival are predominant in ovarian carcinomas compared to those indicating poor clinical outcomes. Specially, we identified 19 (3) predictive MMSs that are, usually by a nonlinear dose-dependent effect, associated with good (poor) patient survival. The false discovery rate for the 19 "positive" predictors is at the level of 0.15. The GO terms corresponding to these MMSs include "lysosomal membrane" and "response to hypoxia", each of which is relevant to the progression and therapy of cancer. Using these MMSs as features, we established a classification tree model which can effectively partition the training samples into three prognosis groups regarding the survival time. We validated this model on an independent dataset of the same disease (Log-rank p-value <2.3×10-4) and a dataset of breast cancer (Log-rank p-value <9.3×10-3). We compared the GO terms corresponding to these MMSs and those enriched with expression-based predictive genes. The analysis showed that the GO term pairs with large similarity are mainly pertinent to the proteins located on the cell organelles responsible for material transport and waste disposal, suggesting the crucial role of these proteins in cancer mortality.
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Benzalkonium chloride suppresses rabbit corneal endothelium intercellular gap junction communication.
PLoS ONE
PUBLISHED: 01-01-2014
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Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if benzalkonium chloride (BAK) alters GJIC activity in the rabbit corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects.
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Comparative metabolite profiling of two rice genotypes with contrasting salt stress tolerance at the seedling stage.
PLoS ONE
PUBLISHED: 01-01-2014
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Rice is sensitive to salt stress, especially at the seedling stage, with rice varieties differing remarkably in salt tolerance (ST). To understand the physiological mechanisms of ST, we investigated salt stress responses at the metabolite level.
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Genotypic diversity analysis of Mycobacterium tuberculosis strains collected from Beijing in 2009, using spoligotyping and VNTR typing.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis (TB) is a serious problem in China. While there have been some studies on the nationwide genotyping of Mycobacterium tuberculosis (M. tuberculosis), there has been little detailed research in Beijing, the capital of China, which has a huge population. Here, M. tuberculosis clinical strains collected in Beijing during 2009 were genotyped by classical methods.
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Normal fibroblasts induce E-cadherin loss and increase lymph node metastasis in gastric cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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A tumor is considered a heterogeneous complex in a three-dimensional environment that is flush with pathophysiological and biomechanical signals. Cell-stroma interactions guide the development and generation of tumors. Here, we evaluate the contributions of normal fibroblasts to gastric cancer.
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Corneal alterations induced by topical application of commercial latanoprost, travoprost and bimatoprost in rabbit.
PLoS ONE
PUBLISHED: 01-01-2014
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Prostaglandin (PG) analogs, including latanoprost, travoprost, and bimatoprost, are currently the most commonly used topical ocular hypotensive medications. The purpose of this study was to investigate the corneal alterations in rabbits following exposure to commercial solution of latanoprost, travoprost and bimatoprost. A total of 64 New Zealand albino rabbits were used and four groups of treatments were constituted. Commercial latanoprost, travoprost, bimatoprost or 0.02% benzalkonium chloride (BAK) was applied once daily to one eye each of rabbits for 30 days. The contralateral untreated eyes used as controls. Schirmer test, tear break-up time (BUT), rose Bengal and fluorescein staining were performed on days 5, 10, 20, and 30. Central corneal changes were analyzed by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance on day 5. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, ?-catenin) proteins, actin cytoskeleton, proliferative marker Ki67 and cell apoptosis in the epithelium. Topical application of commercial PG analogs resulted in significant corneal epithelial and stromal defects while no significant changes in aqueous tear production, BUT, rose bengal and fluorescein staining scores on day 5. Commercial PG analogs induced dislocation of ZO-1 and occludin from their normal locus, disorganization of cortical actin cytoskeleton at the superficial layer, and disruption of epithelial barrier function. The eyes treated with 0.02% BAK and latanoprost exhibited significantly reduced Schirmer scores, BUT, and increased fluorescein staining scores on days 10 and 30, respectively. Topical application of commercial PG analogs can quickly impair the corneal epithelium and stroma without tear deficiency. Commercial PG analogs break down the barrier integrity of corneal epithelium, concomitant with the disruption of cell junction and actin cytoskeleton between superficial cells in the corneal epithelium in vivo.
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Ex-PRESS implantation versus trabeculectomy in open-angle glaucoma: a meta-analysis of randomized controlled clinical trials.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the efficacy and safety of Ex-PRESS implantation (Ex-PRESS) compared to trabeculectomy in the treatment of patients with open-angle glaucoma (OAG).
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UII and UT in grouper: cloning and effects on the transcription of hormones related to growth control.
J. Endocrinol.
PUBLISHED: 10-31-2013
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Urotensin II (UII) is a cyclic peptide that was originally extracted from the caudal neurosecretory system (CNSS) of fish. UII is well known to exhibit cardiovascular, ventilatory, and motor effects in vertebrates. Studies have reported that UII exerts mitogenic effects and can act as an autocrine/paracrine growth factor in mammals. However, similar information in fish is limited. In this study, the full-length cDNAs of UII and its receptor (UT) were cloned and characterized in the orange-spotted grouper. UII and UT were expressed ubiquitously in various tissues in grouper, and particularly high levels were observed in the CNSS, CNS, and ovary. A functional study showed that UT was coupled with intracellular Ca(2)(+) mobilization in HEK293 cells. Studies carried out using i.p. injections of UII in grouper showed the following: i) in the hypothalamus, UII can significantly stimulate the mRNA expression of ghrh and simultaneously inhibit the mRNA expression of somatostatin 1 (ss1) and ss2 3?h after injection; ii) in the pituitary, UII also significantly induced the mRNA expression of gh 6 and 12?h after injection; and iii) in the liver, the mRNA expression levels of ghr1/ghr2 and igf1/igf2 were markedly increased 12 and 3?h after the i.p. injection of UII respectively. These results collectively indicate that the UII/UT system may play a role in the promotion of the growth of the orange-spotted grouper.
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Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride.
Cornea
PUBLISHED: 10-12-2013
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To investigate the effect of benzalkonium chloride (BAK) on corneal nerves.
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Development of a reliable model of total abdominal wall transplantation.
Plast. Reconstr. Surg.
PUBLISHED: 10-01-2013
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Among the most common complications associated with abdominal organ transplantation are issues with abdominal wall closure. This difficulty, along with the recent rise in the use of vascularized composite allotransplantation, has led surgeons to the notion of abdominal wall transplantation.
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[Determination of atracurium and laudanosine in dog plasma during cardiopulmonary bypass by high performance liquid chromatography with fluorometric detection].
Se Pu
PUBLISHED: 09-26-2013
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A high performance liquid chromatographic method coupled with fluorometric detection has been developed for the determination of atracurium and its major metabolite laudanosine in dog plasma. The separation of atracurium and laudanosine was performed on an Agilent Eclipse Plus C18 column, and the mobile phase consisted of 0.03 mol/L dipotassium hydrogen phosphate and acetonitrile (72: 28, v/v) at a flow rate of 1.0 mL/min. Verapamil was used as the internal standard. The sample was extracted by dichloromethane, concentrated and dissolved in the mobile phase. The detection is performed at 240 nm for excitation and 320 nm for emission. The results showed that the linear concentration ranges of the calibration curve were 25 - 5 000 microg/L for atracurium (r = 0.999 0), and 25 - 6 000 microg/L for laudanosine (r = 0.9984). The recoveries were 92.1% - 109.5%. The limits of detection were 3 microg/L for atracurium and 1 microg/L for laudanosine. The RSDs of intra-day and inter-day were less than 10%. The stability tests under various conditions have been performed. The method is specific, sensitive and accurate in the determination of atracurium and laudanosine, and also can be used for the pharmacokinetic investigations of atracurium and laudanosine in plasma.
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[Prolongation of QT interval and evaluation of safety of drugs].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 09-25-2013
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People pay more and more attention to the prolongation of QT interval caused by drugs because it could probably result in lethal arrhythmia. This article introduces mechanisms, risk factors and guidelines for QT interval, and also reviews drugs withdrawal from the market due to the results of prolongations of QT interval. It discusses as well the value of new drugs in the QT interval for the evaluation of safety.
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Design and implementation of frequency-following response recording system.
Int J Audiol
PUBLISHED: 09-23-2013
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The frequency-following response (FFR) is the compound phase-locked brainstem response to periodic components of sound stimuli, and is closely related to pitch perception. Its weak amplitude often prevents its measurement with a high signal-to-noise ratio (SNR). Recording of FFR using multichannel EEG is possible but expensive and it involves the manual screening of raw data.
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One-step generation of different immunodeficient mice with multiple gene modifications by CRISPR/Cas9 mediated genome engineering.
Int. J. Biochem. Cell Biol.
PUBLISHED: 09-14-2013
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Taking advantage of the multiplexable genome engineering feature of the CRISPR/Cas9 system, we sought to generate different kinds of immunodeficient mouse strains by embryo co-microinjection of Cas9 mRNA and multiple sgRNAs targeting mouse B2m, Il2rg, Prf1, Prkdc, and Rag1. We successfully achieved multiple gene modifications, fragment deletion, double knockout of genes localizing on the same chromosome, and got different kinds of immunodeficient mouse models with different heritable genetic modifications at once, providing a one-step strategy for generating different immunodeficient mice which represents significant time-, labor-, and money-saving advantages over traditional approaches. Meanwhile, we improved the technology by optimizing the concentration of Cas9 and sgRNAs and designing two adjacent sgRNAs targeting one exon for each gene, which greatly increased the targeting efficiency and bi-allelic mutations.
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Disturbance of intraepithelial lymphocytes in a murine model of acute intestinal ischemia/reperfusion.
J. Mol. Histol.
PUBLISHED: 08-14-2013
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Strategically located at the epithelial basolateral surface, intraepithelial lymphocytes (IELs) are intimately associated with epithelial cells and maintain the epithelial barrier integrity. Intestinal ischemia-reperfusion (I/R)-induced acute injury not only damages the epithelium but also affects the mucosal barrier function. Therefore, we hypothesized that I/R-induced mucosal damage would affect IEL phenotype and function. Adult C57BL/6J mice were treated with intestinal I/R or sham. Mice were euthanized at 6 h after I/R, and the small bowel was harvested for histological examination and to calculate the transmembrane resistance. Occludin expression and IEL location were detected through immunohistochemistry. The IEL phenotype, activation, and apoptosis were examined using flow cytometry. Cytokine and anti-apoptosis-associated gene expressions were measured through RT-PCR. Intestinal I/R induced the destruction of epithelial cells and intercellular molecules (occludin), resulting in IEL detachment from the epithelium. I/R also significantly increased the CD8??, CD4, and TCR?? IEL subpopulations and significantly changed IEL-derived cytokine expression. Furthermore, I/R enhanced activation and promoted apoptosis in IELs. I/R-induced acute intestinal mucosal damage significantly affected IEL phenotype and function. These findings provide profound insight into potential IEL-mediated epithelial barrier dysfunction after intestinal I/R.
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The training and learning process of transseptal puncture using a modified technique.
Europace
PUBLISHED: 08-14-2013
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As the transseptal (TS) puncture has become an integral part of many types of cardiac interventional procedures, its technique that was initial reported for measurement of left atrial pressure in 1950s, continue to evolve. Our laboratory adopted a modified technique which uses only coronary sinus catheter as the landmark to accomplishing TS punctures under fluoroscopy. The aim of this study is prospectively to evaluate the training and learning process for TS puncture guided by this modified technique.
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Pancreaticobiliary maljuction combining with pancreas divisum: Report of four cases.
Exp Ther Med
PUBLISHED: 07-15-2013
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Pancreaticobiliary maljunction (PBM) is an unusual anomalous condition in which the pancreatic duct and bile duct merge outside the duodenal wall and form a long common channel. Pancreas divisum (PD) is a congenital anomaly in which the dorsal and ventral pancreatic ducts fail to fuse. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosing PD and magnetic resonance cholangiopancreatography (MRCP) is the non-invasive choice. In this study, four cases of patients with unusual PBM in addition to PD are described. The patients presented with abdominal pain, which was caused by distal biliary stricture diagnosed by MRCP. The patients received ERCP and had a good prognosis.
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Tissue Engineering Concept in the Research of the Tumor Biology.
Technol. Cancer Res. Treat.
PUBLISHED: 07-11-2013
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Tumor is a heterogeneous complex, which lives in a three-dimensional environment flush with biopathophysiological and biomechanical signals. This signaling abundant extracellular milieu co-evolving from cell-cell and cell-host interaction guides the development and the generation of the tumor. There has been a recent surge of interest in studying the tumor biology that more closely mirror what happens in living organisms, especially in cancer research. Incorporating cancer cells in the 3D mimicking environment instead of monolayers is reasonable for maintaining in vivo cancer behaviors in spatial and temporal context. However, 3D culture for cancer still presents a challenge for researchers in this field. Tissue engineering, originally aiming at designing the artificial organs, provided a feasible approach to recreate such complex mechanical and biochemical interplay. Aside from reproducing bionic environment, tissue engineering has been routinely introduced into cancer study to build three dimensional structures not only to develop molecular therapeutics, but also to screen for toxic effects of drugs or radiotherapy sensitivity. In this article, we focused on the recent advances of the well-defined tissue-engineering biomaterials in the application in tumor biology. We also discussed the fabrications of the scaffolds from different materials, which might contribute to future cancer research.
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Serine protease inhibitor A3K protects rabbit corneal endothelium from barrier function disruption induced by TNF-?.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-04-2013
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To determine if a serine protease inhibitor A3K (SA3K) reduces TNF-?-induced declines in rabbit corneal endothelial junctional barrier integrity.
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The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT).
Atherosclerosis
PUBLISHED: 06-17-2013
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A total of 102 patients were randomized to either mono-therapy with simvastatin (40 mg daily) or triple-therapy with simvastatin (40 mg daily), extended-release niacin (1500 mg daily), and ezetimibe (10 mg daily). MRI was performed at baseline and 6, 12, and 24 months. SFA wall, lumen, and total vessel volumes were quantified. MRI-derived SFA parameters and lipids were analyzed with multilevel models and nonparametric tests, respectively.
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Molecular insights into the promiscuous interaction of human pregnane X receptor (hPXR) with diverse environmental chemicals and drug compounds.
Chemosphere
PUBLISHED: 06-08-2013
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The nuclear receptor member human pregnane X receptor (hPXR) regulates enzymes and transporters involved in xenobiotic detoxification as well as maintains homeostatic balance of bile acids, thyroid and steroid hormones. hPXR can be recognized and activated by a structurally diverse array of environmental chemicals and drug compounds to initiate adverse biological effects, such as perturbing normal physiological functions and causing dangerous drug-drug interactions and exhibiting a high promiscuity in its ligand spectrum. Understanding of the molecular mechanism and biological implication underlying the promiscuous interaction of hPXR with its diverse ligands is fundamentally important for toxicological and pharmaceutical researches. In the current study, molecular docking and hybrid quantum mechanics/molecular mechanics (QM/MM) were employed to investigate the binding mode, structural basis and energetic property of hPXR interactions with various activators and non-activators. It was found that, as compared to non-activators, the activators adopt few dominant modes to tightly interact with hPXR, which are specified by few polar spots located on the hydrophobic surface of hPXR active pocket. Based on the findings, a novel method called multiple binding mode-based quantitative structure-activity relationship (MBMB-QSAR) that characterizes the nonbonded interaction profile of hPXR with its ligand in multiple binding modes was proposed to model and predict the activating potency of small-molecule compounds on hPXR. Several partial least square (PLS) predictors derived from the MBMB-QSAR modeling were demonstrated to be effective for quantitative characterization of the biological behavior of experimentally confirmed activators, and for qualitatively differentiating the activators from a large number of non-activators. From the predictor models it is suggested that the hydrophobic force and electrostatic interaction play an important role in hPXR-ligand binding, while steric factor contributes moderately to the binding.
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Discriminative Object Tracking via Sparse Representation and Online Dictionary Learning.
IEEE Trans Cybern
PUBLISHED: 05-31-2013
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We propose a robust tracking algorithm based on local sparse coding with discriminative dictionary learning and new keypoint matching schema. This algorithm consists of two parts: the local sparse coding with online updated discriminative dictionary for tracking (SOD part), and the keypoint matching refinement for enhancing the tracking performance (KP part). In the SOD part, the local image patches of the target object and background are represented by their sparse codes using an over-complete discriminative dictionary. Such discriminative dictionary, which encodes the information of both the foreground and the background, may provide more discriminative power. Furthermore, in order to adapt the dictionary to the variation of the foreground and background during the tracking, an online learning method is employed to update the dictionary. The KP part utilizes refined keypoint matching schema to improve the performance of the SOD. With the help of sparse representation and online updated discriminative dictionary, the KP part are more robust than the traditional method to reject the incorrect matches and eliminate the outliers. The proposed method is embedded into a Bayesian inference framework for visual tracking. Experimental results on several challenging video sequences demonstrate the effectiveness and robustness of our approach.
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Numb modulates the paracellular permeability of intestinal epithelial cells through regulating apical junctional complex assembly and myosin light chain phosphorylation.
Exp. Cell Res.
PUBLISHED: 05-08-2013
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Numb is highly expressed throughout the crypt-villus axis of intestinal mucosa and functions as cell fate determinant and integrator of cell-to-cell adhesion. Increased paracellular permeability of intestinal epithelial cells is associated with the epithelial barrier dysfunction of inflammatory bowel diseases (IBDs). The apical junctional complex (AJC) assembly and myosin light chain (MLC) phosphorylation regulate adherens junctions (AJ) and tight junctions (TJ). We determined whether and how Numb modulate the paracellular permeability of intestinal epithelial cells. Caco-2 intestinal epithelial cells and their Numb-interfered counterparts were used in the study for physiological, morphological and biological analyses. Numb, expressed in intestinal epithelial cells and located at the plasma membrane of Caco-2 cells in a basolateral to apical distribution, increased in the intestinal epithelial cells with the formation of the intestinal epithelial barrier. Numb expression decreased and accumulated in the cytoplasm of intestinal epithelial cells in a DSS-induced colitis mouse model. Numb co-localized with E-cadherin, ZO-1 and Par3 at the plasma membrane and interacted with E-cadherin and Par3. Knockdown of Numb in Caco-2 cells altered the F-actin structure during the Ca(2+) switch assay, enhanced TNF?-/INF-?-induced intestinal epithelial barrier dysfunction and TJ destruction, and increased the Claudin-2 protein level. Immunofluorescence experiments revealed that NMIIA and F-actin co-localized at the cell surface of Caco-2 cells. Numb knockdown in Caco-2 cells increased F-actin contraction and the abundance of phosphorylated MLC. Numb modulated the intestinal epithelial barrier in a Notch signaling-independent manner. These findings suggest that Numb modulates the paracellular permeability by affecting AJC assembly and MLC phosphorylation.
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SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.
Free Radic. Biol. Med.
PUBLISHED: 04-21-2013
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Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling.
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Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides).
Mol. Cell. Endocrinol.
PUBLISHED: 04-11-2013
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Somatostatin is the most effective inhibitor of GH release, and GHRH was recently identified as one of the primary GH-releasing factors in teleosts. In this study, we analyzed the possible intracellular transduction pathways that are involved in the mechanisms induced by SRIF and GHRH to regulate GH release. Using a pharmacological approach, the blockade of the PLC/IP/PKC pathway reversed the SRIF-induced inhibition of GH release but did not affect the GHRH-induced stimulation of GH release. Furthermore, SRIF reduced the GH release induced by two PKC activators. Inhibitors of the AC/cAMP/PKA pathway reversed both the SRIF- and GHRH-induced effects on GH release. Moreover, the GH release evoked by forskolin and 8-Br-cAMP were completely abolished by SRIF. The blockade of the NOS/NO pathway attenuated the GHRH-induced GH release but had minimal effects on the inhibitory actions of SRIF. In addition, inhibitors of the sGC/cGMP pathway did not modify the SRIF- or GHRH-induced regulation of GH release. Taken together, these findings indicate that the SRIF-induced inhibition of GH release is mediated by both the PLC/IP/PKC and the AC/cAMP/PKA pathways and not by the NOS/NO/sGC/cGMP pathway. In contrast, the GHRH-induced stimulation of GH secretion is mediated by both the AC/cAMP/PKA and the NOS/NO pathways and is independent of the sGC/cGMP pathway and the PLC/IP/PKC system.
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JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury.
J. Pineal Res.
PUBLISHED: 03-28-2013
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Ischemia/reperfusion injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Numerous data indicate that the JAK2/STAT3 signaling pathway is specifically involved in preventing myocardial IRI. Melatonin has potent activity against IRI and may regulate JAK2/STAT3 signaling. This study investigated the protective effect of melatonin pretreatment on myocardial IRI and elucidated its potential mechanism. Perfused isolated rat hearts and cultured neonatal rat cardiomyocytes were exposed to melatonin in the absence or presence of the JAK2/STAT3 inhibitor AG490 or JAK2 siRNA and then subjected to IR. Melatonin conferred a cardio-protective effect, as shown by improved postischemic cardiac function, decreased infarct size, reduced apoptotic index, diminished lactate dehydrogenase release, up-regulation of the anti-apoptotic protein Bcl2, and down-regulation of the pro-apoptotic protein Bax. AG490 or JAK2 siRNA blocked melatonin-mediated cardio-protection by inhibiting JAK2/STAT3 signaling. Melatonin exposure also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase (SOD) activity, and decreased formation of mitochondrial hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA), which indicates that the IR-induced mitochondrial oxidative damage was significantly attenuated. However, this melatonin-induced effect on mitochondrial function was reversed by AG490 or JAK2 siRNA treatment. In summary, our results demonstrate that melatonin pretreatment can attenuate IRI by reducing IR-induced mitochondrial oxidative damage via the activation of the JAK2/STAT3 signaling pathway.
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Transplantation of NSCs with OECs alleviates neuropathic pain associated with NGF downregulation in rats following spinal cord injury.
Neurosci. Lett.
PUBLISHED: 03-27-2013
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Spinal cord injury (SCI) is a common and serious disease which often induces catastrophic consequence in patients. Part of them exhibit neuropathic pain which presents unique challenges to clinicians, and there is no effective approach for the treatment up to now. Neural stem cells (NSCs) transplantation, as a promising and an effective method, could be considered for the treatment of SCI, whereas a main problem is the low survival of NSCs in traumatic milieu in host spinal cords, and the effect of NSCs on sensory function remains elusive. In this study, we investigated the effect and underlying molecular mechanism of co-transplantation of NSCs with olfactory ensheathing cells (OECs) on sensory functional improvement. In the measurement of thermal and mechanical stimuli, NSCs grafts recovered sensory function in SCI rats, while OECs led to hyperalgesia, indicated by the tail flick latency (TFL) and paw withdraw latency (PWL) (p<0.05). Co-transplantation could promote NSCs survival, and reverses the hyperalgesia triggered by OECs. This was corresponding to a significant improvement in sensory function. Moreover, NGF expression was substantial downregulated in the spinal cord of co-transplantation rats. The present findings suggested that co-transplantation of NSCs with OECs could improve sensory function and the possible mechanism is involved in NGF downregulation in rats with SCI. This may give some new indications for the treatment of SCI in future clinic cell therapy trial.
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[Occurrence and prognosis of coronary slow flow in emergency percutaneous coronary intervention: correlations with homocysteine].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 03-27-2013
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To investigate the correlation of the occurrence and prognosis of coronary slow flow phenomenon (CSF) with blood homocysteine (Hcy) levels in patients receiving emergency percutaneous coronary intervention therapy (PCI).
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