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Find video protocols related to scientific articles indexed in Pubmed.
Risk factors of hyperammonemia in patients with epilepsy under valproic acid therapy.
Medicine (Baltimore)
PUBLISHED: 09-06-2014
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Hyperammonemia has been reported to be associated with patients who receive valproic acid (VPA) therapy. This study aimed to determine the risk factors for hyperammonemia in patients with epilepsy treated with VPA. One hundred and fifty-eight adult patients with epilepsy aged older than 17 years who received VPA therapy were enrolled into this study. Blood samples were taken during the interictal state and analyzed for the blood level of ammonia. Statistical analysis was conducted between different groups of patients. The results showed that the frequency of hyperammonemia associated with VPA therapy was 27.8% (ammonia level >93?µg/dL), and 5.1% of the patients had severe hyperammonemia (ammonia level >150?µg/dL). The blood ammonia level was significantly correlated with the dosage of VPA and the plasma concentration of VPA. An increase of 1?mg in the dosage of VPA increased the risk of hyperammonemia by 0.1%. In addition, combination treatment with liver enzyme inducing antiepileptic drugs (AEDs) and antipsychotic drugs increased the risk of hyperammonemia. In conclusion, the use of VPA in adult patients with epilepsy was associated with a dose-dependent increase in blood concentrations of ammonia. Combination treatment with liver enzyme-inducing AEDs and antipsychotic drugs increased the risk of VPA-induced hyperammonemia. Most of the patients with VPA-induced hyperammonemia were asymptomatic; however, if patients taking VPA present with symptoms such as nausea, fatigue, somnolence, ataxia, and consciousness disturbance, the blood ammonia level should be measured.
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Systematic review of traditional chinese medicine for depression in Parkinson's disease.
Am. J. Chin. Med.
PUBLISHED: 09-03-2014
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Depression is the most common non-motor symptom of Parkinson's disease (PD). Recent clinical trials have evaluated the effectiveness of traditional Chinese medicine (TCM) in the treatment of depression in PD (dPD). However, the results are conflicting rather than conclusive. To investigate the effectiveness of TCM for the treatment of dPD, a systematic review was conducted. Literature searches and collections were performed to identify studies addressing the treatment of TCM for dPD. The methodological quality and risk of bias in all studies included were evaluated. Weighted mean difference (WMD) with 95% confidence interval (CI) was used as the effect measure. Finally, a total of 10 studies involving 582 patients were identified. The pooled results revealed that TCM combined with conventional drugs significantly improved the total scores of the unified Parkinson's disease rating scale (WMD = -7.35, 95% CI: -11.24 to -3.47) and the score of the Hamilton rating scale for depression (HAM-D) (WMD = -4.19, 95% CI: -5.14 to -3.24) compared with conventional drug, respectively. Conclusively, there is evidence that TCM may be beneficial to the treatment of dPD in spite of the methodological weakness of the included studies.
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Bioactive furanocoumarins from stems of Clausena lansium.
Phytochemistry
PUBLISHED: 08-26-2014
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Clausena lansium Skeels, a member of the Rutaceae, is a shrub or small tree with grapelike fruits. Several parts of this plant have been used in folk medicine. A bioactive constituent investigation of the stems of C. lansium herein resulted in isolation of four furanocoumarins, claucoumarins A-D, and 13 known analogs. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, MS, and NMR experiments, and their absolute configurations were determined by CD experiments. Using an in vitro system, several of these compounds showed selective neuroprotective effects at a concentration of 10?M.
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Specific siRNA Inhibits XIAP Expression in Human Endometrial Carcinoma Cell Apoptosis.
Cell Biochem. Biophys.
PUBLISHED: 08-24-2014
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The aim of the study was to investigate the inhibitory effects of RNA interference on XIAP gene expression of human endometrial carcinoma RL95-2 cell and the cell apoptosis. Specific small interference RNA (siRNA) of XIAP was designed and composed. Transfection of siRNA was conducted in endometrial carcinoma cell line RL95-2. The XIAP gene mRNA was assessed by real-time PCR and the change of XIAP protein was assessed with Western Blotting. The cell proliferation and apoptosis was assessed by MTT and flow cytometry methods. After transfection of siRNA specifically targeting XIAP, the relative fold of mRNA transfection in the specific transfection group was (0.04 ± 0.06) and the relative protein expression was (0.590 ± 0.178), which was significantly decreased when compared with the control group (P < 0.05); the cell growth inhibition rate in the transfection group was (47.86 ± 4.46) %, which was significantly increased when compared to the control group (P < 0.05). In vitro experiment showed that synthetic siRNA could effectively inhibit the transfection and expression of XIAP gene of human endometrial carcinoma RL95-2 cell at the mRNA level and protein level, thus significantly promote the apoptosis of endometrial carcinoma cell. The mechanisms involved in the apoptosis still require further investigation.
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Chemokine-like factor 1 promotes the migration of rat primary cortical neurons by the induction of actin polymerization.
Neuroreport
PUBLISHED: 08-22-2014
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Chemokine-like factor 1 (CKLF1), a newly cloned chemotactic cytokine, plays an essential role in immune cell migration. However, the potential role of CKLF1 in the cortical neuronal migration remains unclear. In the present research, by measuring the distance between the margin of brain slices and the leading population of migrating cells, we showed that the extent of cell migration was markedly enhanced in response to CKLF1 treatment, which was significantly inhibited by the simultaneous addition of anti-CKLF1 antibody. By immunofluorescence staining, it was found that CKLF1 induced actin polymerization in primary cerebral cortical neurons. By wound-healing assays, it was found that CKLF1 stimulated the migration of cortical neurons in a dose-dependent manner. In conclusion, our data suggest that CKLF1 promotes the migration of rat primary cerebral cortical neurons by the induction of actin polymerization.
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The real-time method of assessing the contribution of individual sources on visibility degradation in Taichung.
Sci. Total Environ.
PUBLISHED: 08-15-2014
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Visibility degradation caused by air pollution has become a serious environmental problem in megacities in Northeast Asia. In general, aerosol chemical compositions are measured by a conventional method of time integrated filter sampling for off-line analysis, which cannot represent temporal and spatial variations in the real atmosphere. The in situ air composition measuring equipment, OCEC carbon aerosol analyzer and a long-path visibility transmissometer-3 were used to collect hourly measurements of the soluble ions, organic/elemental carbon, and ambient visibility, respectively. During the observation, two types of weather conditions were identified: transport and stagnant. Because PM2.5 was identified as the predominant species of light extinction, the sources of PM2.5 were determined and investigated using a positive matrix factorization (PMF) analysis. The PMF outputs characterized the six main emission sources (marine/crustal aerosols, secondary nitrate, secondary sulfate, direct vehicle exhaust, coal/incinerator combustion, and local sewage emission) and reconstructed the PM2.5 mass concentrations of each pollutant source in two weather conditions. In addition, the light extinction (bext) was reconstructed using a multivariate linear regression analysis with hourly-reconstructed PM2.5 mass concentrations to determine the contributions of each source to bext. The primary results showed that the extinction coefficient was proportional to the PM2.5 with high value in stagnant weather conditions. The secondary sulfate was the most abundant source of bext contribution during the sampling period. In addition, the bext contributions of direct vehicle exhaust and coal/incinerator combustion significantly increased in the stagnant weather condition. According to the results of hourly measurements, this work further emphasized that the sources of direct vehicle exhaust and coal/incinerator combustion in PM2.5 were the important sources of visibility degradation in the stagnant weather conditions, which suggests that the pollutants derived from direct vehicle exhaust and coal/incinerator combustion should be controlled first to improve visibility in Taichung.
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Reconstruction for osteoradionecrosis of the mandible: superiority of free iliac bone flap to fibula flap in postoperative infection and healing.
Ann Plast Surg
PUBLISHED: 08-14-2014
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Osteoradionecrosis (ORN) of the mandible is not an uncommon complication after radiotherapy for head and neck cancers. Although definitive treatment has been confirmed as radical excision of the necrotic bone with simultaneous vascularized osteocutaneous flap reconstruction, it remains a unique challenge. In this study, we compare our results of reconstruction with free iliac and fibula flaps in flap survival, bony union, and postoperative complications.
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Polygalasaponin F inhibits secretion of inflammatory cytokines via NF-?B pathway regulation.
J Asian Nat Prod Res
PUBLISHED: 08-01-2014
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To study the anti-neuroinflammatory mechanisms of polygalasaponin F (PS-F), ELISA method was used to detect the secretion of inflammatory cytokines. Western blot was used to detect the protein expression and phosphorylation levels. Immunofluorescence assay was used to observe the NF-?B nuclear translocation. PS-F could inhibit the release of inflammatory cytokines TNF-? and NO induced by lipopolysaccharides (LPS) and reduce the expression of inducible nitric oxide synthases (iNOS). As for MAPK-signaling pathway, PS-F could only inhibit the phosphorylation levels of p38 MAPK, but did not significantly affect the phosphorylation levels of JNK and ERK1/2 protein kinases. PS-F could inhibit NF-?B nuclear translocation in a dose-dependent manner. The results of Western blot assay were consistent with immunofluorescence assays. Meanwhile, p38-specific inhibitor SB203580 (20 ?M) and p65-specific inhibitor PDTC (100 ?M) were, respectively, administered as a positive control. In addition, PS-F could significantly inhibit the cytotoxicity of conditioned medium prepared by LPS-stimulated BV-2 microglia (LPS conditioned media) to neuronal PC12 cells and improve cell viability. PS-F inhibits the secretions of neuroinflammatory cytokines by the regulation of NF-?B-signaling pathway.
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Three-dimensional extracellular matrix scaffolds by microfluidic fabrication for long-term spontaneously contracted cardiomyocyte culture.
Tissue Eng Part A
PUBLISHED: 07-22-2014
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To repair damaged cardiac tissue, the important principle of in vitro cell culture is to mimic the in vivo cell growth environment. Thus, micro-sized cells are more suitably cultured in three-dimensional (3D) than in two-dimensional (2D) microenvironments (ex: culture dish). With the matching dimensions of works produced by microfluidic technology, chemical engineering and biochemistry applications have used this technology extensively in cellular works. The 3D scaffolds produced in our investigation has essential properties, such has high mass transfer efficiency, and variable pore sizes, to adapt to various needs of different cell types. In addition to the malleability of these innovative scaffolds, fabrication procedure was effortless and fast. Primary neonatal mice cardiomyocytes were successfully harvested and cultured in 3D scaffolds made of gelatin and collagen. Gelatin and gelatin-collagen scaffold were produced by the formation of microbubbles through a microfluidic device, and the mechanical properties of gelatin scaffold and gelatin-collagen scaffold were measured. Cellular properties in the microbubbles were also monitored. Fluorescence staining results assured that cardiomyocytes could maintain in vivo morphology in 3D gelatin scaffold. In addition, it was found that 3D scaffold could prolong the contraction behavior of cardiomyocytes compared with a conventional 2D culture dish. Spontaneously contracted behavior was maintained for the longest (about 1 month) in the 3D gelatin scaffold, about 19 days in the 3D gelatin-collagen scaffold. To sum up, this 3D platform for cell culture has promising potential for myocardial tissue engineering.
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[Good agricultural practice (GAP) of Chinese materia medica (CMM) for ten years: achievements, problems and proposals].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-12-2014
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This paper aims to summarize the achievements during the implementation process of good agricultural practice (GAP) in Chinese Materia Medica (CMM), and on basis of analyzing the existing problems of GAP, to propose further implementation of GAP in TCM growing. Since the launch of GAP in CMM growing ten years ago, it has acquired great achievements, including: (1) The promulgation of a series of measures for the administration of the GAP approval in the CMM growing; (2) The expanded planting area of CMM; (3) The increased awareness of standardized CMM growing among farmers and enterprises; (4) The establishment of GAP implementation bases for CMM growing; (5) The improvement of theory and methodology for CMM growing; (6) The development of a large group of experts and scholars in GAP approval for CMM production. The problems existing in the production include: (1) A deep understanding of GAP and its certification is still needed; (2) The distribution of the certification base is not reasonable; (3) The geo-economics effect and the backward farming practices are thought to be the bottlenecks in the standardization of CMM growing and the scale production of CMM; (4) Low comparative effectiveness limits the development of the GAP; (5) The base of breeding improved variety is blank; (6) The immature of the cultivation technique lead to the risk of production process; (7) The degradation of soil microbial and the continuous cropping obstacle restrict the sustainable development of the GAP base. To further promote the health and orderly GAP in the CMM growing, the authors propose: (1) To change the mode of production; (2) To establish a sound standard system so as to ensure quality products for fair prices; (3) To fully consider the geo-economic culture and vigorously promote the definite cultivating of traditional Chinese medicinal materials; (4) To strengthen the transformation and generalization of basic researches and achievements, in order to provide technical support for the CMM production; (5) To deepen the understanding of GAP, to vigorously promote ecological planting and precision agriculture, in order to overcome the continuous cropping obstacle. The authors think that despite the fact that we are still facing with a huge array of management and technological problems, the GAP in the CMM growing has already enjoyed widespread support and showed great potential. In the future, with people's deeper understanding of GAP and the great progress of the science and technology, the GAP will constantly be fused with the theory, methodology and technology in the modern agriculture like precision agriculture, eco-agriculture and etc.
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Causes of death among persons who survive an acute ischemic stroke.
Curr Neurol Neurosci Rep
PUBLISHED: 06-22-2014
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Stroke and especially its complications are a leading cause of death. Despite reduced morbidity in some developed countries, mortality in stroke patients is still high worldwide. In the past decades, treatment of acute stroke has focused on early intervention, such as revascularization and cerebral edema prevention. However, long-term clinical observations indicate that poststroke pneumonia, cardiovascular complications, and vascular embolism are the major reasons for the increased death rate after stroke. Few evidence-based data are available currently to guide the management of these complications. Thus, systematic studies of these adverse events are essential and urgent to improve survival after stroke.
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Overexpression of human E46K mutant ?-synuclein impairs macroautophagy via inactivation of JNK1-Bcl-2 pathway.
Mol. Neurobiol.
PUBLISHED: 04-30-2014
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Parkinson's disease (PD) is pathologically characterized by selective loss of dopaminergic neurons in the midbrain and the existence of intracellular protein inclusions termed Lewy bodies, largely composed of ?-synuclein. Genetic studies have revealed that rare point mutations in the gene encoding ?-synuclein including A30P, A53T, and E46K are associated with familial forms of PD, indicating a pathological role for mutant ?-synuclein in PD etiology. However, the mechanisms underlying the neuronal toxicity of mutant ?-synuclein are still to be elucidated. Growing evidence has suggested a deleterious effect of mutant ?-synuclein on the autophagy-lysosome pathway. In this study, we discovered that overexpression of human E46K mutant ?-synuclein impaired macroautophagy in mammalian cells. Our data showed that overexpression of E46K mutant ?-synuclein impaired autophagy at an early stage of autophagosome formation via the c-Jun N-terminal kinase 1 (JNK1)-Bcl-2 but not the mammalian target of rapamycin (mTOR) pathway. Overexpressed E46K mutant ?-synuclein inhibited JNK1 activation, leading to a reduced Bcl-2 phosphorylation and increased association between Bcl-2 and Beclin1, further disrupting the formation of Beclin1/hVps34 complex, which is essential for autophagy initiation. Furthermore, overexpression of E46K mutant ?-synuclein increased the vulnerability of differentiated PC12 cells to rotenone treatment, which would be partly due to its inhibitory effects on autophagy. Our findings may shed light on the potential roles of mutant ?-synuclein in the pathogenesis of PD.
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Inhibition of chemokine-like factor 1 protects against focal cerebral ischemia through the promotion of energy metabolism and anti-apoptotic effect.
Neurochem. Int.
PUBLISHED: 04-27-2014
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Chemokine-like factor 1 (CKLF1) is a novel C-C chemokine, and plays important roles in immune response and brain development. In previous study, we have found that the expression of CKLF1 increased after focal cerebral ischemia and inhibition of CKLF1 using antagonist C19 peptide protected against cerebral ischemia. However, few studies have focused on the role of CKLF1 on neuronal apoptosis. The objective of present study is to investigate the role of CKLF1 on neuronal apoptosis by applying anti-CKLF1 antibodies in rat focal cerebral ischemia and reperfusion model. Antibodies against CKLF1 was applied to the right cerebral ventricle immediately after transient middle cerebral artery occlusion (MCAO), and infarct volume, neurological score, glucose metabolism and apoptosis-related protein were measured. Treatment with anti-CKLF1 antibody decreased infarct volume and neurological score, and inhibited neuronal apoptosis in a dose-dependent manner at 24h after reperfusion. Anti-CKLF1 antibody also reduced the level of phosphorylation of Akt (P-Akt), and led to decrease of pro-apoptotic protein Bcl-2 associated X protein (Bax) and increase of anti-apoptotic protein B cell lymphoma-2 protein (Bcl-2) and the ratio of Bcl-2/Bax, and inhibited caspase-3 at last. In addition, positron emission tomography (PET) indicated that anti-CKLF1 antibody increased glucose metabolism in ischemic hemisphere. These results suggest that CKLF1 is associated with neuronal apoptosis after cerebral ischemia and reperfusion. Neutralization of CKLF1 with antibodies shows neuroprotective effects against cerebral ischemia, which may be involved in inhibition of Akt pathway, regulation of apoptosis-related protein expression, and improvement glucose metabolism in ischemic hemisphere. Therefore, CKLF1 may be a novel target for the treatment of stroke.
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IMM-H004, a novel coumarin derivative compound, attenuates the production of inflammatory mediatory mediators in lipopolysaccharide-activated BV2 microglia.
Brain Res. Bull.
PUBLISHED: 04-24-2014
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Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a novel compound and has been reported exerting potent neuroprotective effects which may be related to anti-inflammation. In the present study, the anti-inflammatory effects of IMM-H004 were investigated in lipopolysaccharide (LPS)-treated BV2 microglia. Our observations indicated that treatment with IMM-H004 significantly inhibited BV2 microglia activation, protected PC12 cells and primary neurons against indirect toxicity mediated by exposure to conditioned medium (CM) from LPS-treated BV2 cells. Additionally, IMM-H004 significantly suppressed the release of TNF-?, IL-1? and NO, and suppressed the expression of pro-inflammatory mediators and cytokines such as iNOS, COX-2, and IL-6 in LPS-stimulated BV2 microglia. The nuclear translocation of NF-?B and the phosphorylation level of JNK and p38 MAPK pathways were also inhibited by IMM-H004 in LPS-treated BV2 microglia. Moreover, IMM-H004 also was a strong selective OH scavenger whose effect was similar with vitamin C. Overall, our findings suggested that IMM-H004 might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation.
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Racial and Ethnic Disparities in Salivary Gland Cancer Survival.
JAMA Otolaryngol Head Neck Surg
PUBLISHED: 04-19-2014
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IMPORTANCE Several recent US studies have documented racial disparities in head and neck cancer outcomes, but few have investigated racial and ethnic differences in salivary gland cancer (SGCA) survival. OBJECTIVE To determine whether patient race or ethnicity affects SGCA survival. DESIGN, SETTING, AND PARTICIPANTS Retrospective survival analysis of all patients with SGCA from 1988 through 2010 in the Surveillance, Epidemiology, and End Results database. MAIN OUTCOMES AND MEASURES Disease-specific survival according to race and ethnicity. End points assessed included age at diagnosis, sex, tumor grade, tumor size at diagnosis, extension at diagnosis, lymph node involvement at diagnosis, and treatment. Results were further analyzed by histologic subtype of SGCA. RESULTS Of 11?007 patients with SGCA, 1073 (9.7%) were black, and 1068 (9.7%), Hispanic. Whites' mean age at diagnosis was 63 years vs 53 and 52 years for blacks and Hispanics, respectively (P?<?.001). Twenty-year disease-specific survival rates for all SGCA histologic subtypes combined for whites, blacks, and Hispanics were 78%, 79%, and 81%, respectively. Unadjusted survival curves showed no significant difference between blacks and whites and an apparent advantage for Hispanics. However, multivariable Cox regression models controlling for patient, tumor, and treatment characteristics showed poorer disease-specific survival vs whites for blacks (hazard ratio [HR], 1.22 [95% CI, 1.03-1.46]; P?=?.03) but not for Hispanics (HR, 0.97 [0.79-1.19]; P?=?.77). The overall disease-specific survival disparity was due to poorer disease-specific survival for blacks vs whites with mucoepidermoid (P?=?.03) and squamous cell carcinomas (P?=?.05). Less surgical treatment for blacks than whites (57.26% vs 76.94%; P?<?.001) was a source of the survival disparity for squamous cell but not mucoepidermoid SGCA. CONCLUSIONS AND RELEVANCE Black race is a risk factor for poorer disease-specific survival for patients with mucoepidermoid or squamous cell carcinoma, whereas Hispanic ethnicity has no effect. Differing treatment between black and white patients affects survival in squamous cell but not mucoepidermoid SGCA. Differences in chemotherapy treatment, comorbidities, socioeconomic status, tumor genetic factors, and environmental exposures are potential but unproven additional sources of the racial survival disparities for mucoepidermoid and squamous cell SGCA.
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Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D.
Cancer Discov
PUBLISHED: 04-02-2014
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Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote Kras(G12D)-driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in Kras(G12D) mice, whereas genetic or pharmacologic ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer-promoter communications at jointly regulated genes involved in oncogenesis, for example, Cyclin, EGFR and WNT family members. The NFATc1-STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory-driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs that are currently available for targeting these factors in clinical trials.
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Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner: the role of inhibition of Drp1 in ischemic brain damage.
Neuropharmacology
PUBLISHED: 03-31-2014
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Mitochondria dysfunction is implicated in diverse conditions, including metabolic and neurodegenerative disorders. Mitochondrial dynamics has attracted increasing attention as to its relationship with mitochondria autophagy, also known as mitophagy, which is critical for degradation of dysfunctional mitochondria maintaining mitochondrial homeostasis. Mitochondrial ?ssion and its role in clearance of injured mitochondria in acute ischemic injury, however, have not been elucidated yet. Here we showed that hypoxic/ischemic conditions led to fragmentation of mitochondria and induction of mitophagy in permanent middle cerebral artery occlusion (pMCAO) rats and oxygen-glucose deprivation (OGD) PC12 cells. Inhibition of Drp1 by pharmacologic inhibitor or siRNA resulted in accumulation of damaged mitochondria mainly through selectively blocking mitophagy without affecting mitochondrial biogenesis and non-selective autophagy. Drp1 inhibitors increased the infarct volume and aggravated the neurological de?cits in a rat model of pMCAO. We demonstrated that the devastating role of disturbed mitochondrial fission by inhibiting Drp1 contributed to the damaged mitochondria-mediated injury such as ROS generation, cyt-c release and activation of caspase-3. Taken together, we proved that under hypoxic/ischemic stress a Drp1-dependent mitophagy was triggered which was involved in the removal of damaged mitochondria and cellular survival at the early stage of hypoxic/ischemic injury. Thus, Drp1 related pathway involved in selective removal of dysfunctional mitochondria is proposed as an efficient target for treatment of cerebral ischemia.
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An open-label, prospective pilot clinical study of denosumab for severe hyperparathyroidism in patients with low bone mass undergoing dialysis.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-26-2014
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Denosumab is widely used for bone diseases with increased bone resorption. Its effectiveness in patients with severe secondary hyperparathyroidism on dialysis is unclear.
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?-Synuclein is prone to interaction with the GC-box-like sequence in vitro.
Cell. Mol. Neurobiol.
PUBLISHED: 03-07-2014
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?-Synuclein (?-syn) is a presynaptic protein that is widely implicated in the pathophysiology of Parkinson's disease, a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons and the formation of Lewy bodies. Evidence suggests that ?-syn could be imported into the nucleus and subsequently disrupt normal neuronal function. The existence of ?-syn in the nucleus provides the possibility of interaction with DNA leading to gene transcript regulation. Thus, CD spectra were used to determine the specific DNA sequence with which ?-syn is most likely to interact. Our results indicated that ?-syn was prone to preferentially interact with the GC-box-like sequence in vitro at a ratio of 2:1 or less (?-syn: the GC-box-like sequence).
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Cerebral glucose transporter: the possible therapeutic target for ischemic stroke.
Neurochem. Int.
PUBLISHED: 03-02-2014
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Hyperglycemia is considered to be associated with poor outcomes of ischemic stroke. However, it is controversial about the blood glucose-lowering therapy in patients with stroke. According to the current reports, hyperglycemia is an indicator of severe stroke and cannot increase cerebral glucose content but promotes further ischemia in brain. Consequently, cerebral glucose control is significant to maintain the energy homeostasis. Compared with blood glucose level, the cerebral glucose content, controlled by glucose transporters (GLUTs), is more directly and important to maintain the energy supply in brain, especially to the patients with ischemic stroke. Some active materials, such as Glucagon-like peptide-1, progesterone, tPA and N-acetylcysteine, have been found to ameliorate ischemic stroke by regulating GLUTs expression. Therefore, this review discusses the significance of cerebral glucose level and GLUTs. Additionally, cerebral GLUTs and their actions in ischemic stroke are detailed in order to promote research on GLUTs as a possible therapeutic target for ischemic stroke.
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Maintenance of human adipose derived stem cell (hASC) differentiation capabilities using a 3D culture.
Biotechnol. Lett.
PUBLISHED: 02-20-2014
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In this study, 3D culture system for human adipose-derived stem cell (hASC) using a BioLevitator as the bioreactor for microcarrier-based cultures was established. During the culturing period, hASCs preferred to grow in crevices between microcarriers and a high viability was maintained even when reaching confluency. Adipogenic or osteogenic differential medium was used to induce hASCs and differential potentials of these cells were compared between 2D and 3D environments via RT-PCR and staining quantifications. CEBP/? gene expression was significant higher in 3D condition at day 21 (P < 0.05). Staining quantification indicates that cells cultured in 3D condition have significant better differentiation potential from day 14 to 21 for both adipogenic and osteogenic lineages (P < 0.01).
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The chemokine-like factor 1 induces asthmatic pathological change by activating nuclear factor-?B signaling pathway.
Int. Immunopharmacol.
PUBLISHED: 02-13-2014
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CKLF1, which exhibits chemotactic activities on a wide spectrum of leukocytes, is up-regulated during the progress of asthma. It plays a vital role in the pathogenesis of pulmonary disease. Here, we report that CKLF1 has the capability to activate the NF-?B signaling pathway leading to the pathological change in the lung. The HEK293-CCR4 cell line, which expressed CCR4 stably, was established and screened. Western blot analysis was performed to determine the expression of NF-?B in HEK293-CCR4 and A549 cells following the C27 (10?g/ml) added in each well at different times. These results showed that C27 (10?g/ml) time-dependently induced the accumulation of NF-?B in the nucleus of HEK293-CCR4 and A549 cells. In addition, CKLF1 plasmid (100?g) injection and electroporation led to the asthmatic change in the lung in mice as shown by HE and PAS staining. Furthermore, it was confirmed that CKLF1 significantly up-regulated the p-I?B expression, decreased the I?B expression, and suppressed the NF-?B expression in the cytoplasm of pulmonary tissue in vivo study. Intriguingly, an enhanced nuclear accumulation of NF-?B was observed in the lung of pCDI-CKLF1 electroporated mice, compared to that in the sham group. Therefore, the NF-?B signaling pathway was involved in the asthmatic change induced by CKLF1, among which CCR4 might play a crucial role.
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The effect of hyperoxia on survival following adult cardiac arrest: a systematic review and meta-analysis of observational studies.
Resuscitation
PUBLISHED: 02-08-2014
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Studies have shown the detrimental effect of hyperoxia in animals with return of spontaneous circulation (ROSC) after cardiac arrest. To maximize the value of existing clinical studies, we performed the systemic review and meta-analysis of human observational studies to examine the effect of hyperoxia on outcomes of post-ROSC patients.
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Neutralization of chemokine-like factor 1, a novel C-C chemokine, protects against focal cerebral ischemia by inhibiting neutrophil infiltration via MAPK pathways in rats.
J Neuroinflammation
PUBLISHED: 02-03-2014
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Inflammation plays a key role in the pathophysiology of ischemic stroke. Some proinflammatory mediators, such as cytokines and chemokines, are produced in stroke. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, displays chemotactic activities in a wide spectrum of leukocytes and plays an important role in brain development. In previous studies, we have found that the expression of CKLF1 increased in rats after focal cerebral ischemia and treatment with the CKLF1 antagonist C19 peptide decreased the infarct size and water content. However, the role of CKLF1 in stroke is still unclear. The objective of the present study was to ascertain the possible roles and mechanism of CKLF1 in ischemic brain injury by applying anti-CKLF1 antibody.
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The transcriptional repression activity of STAF65? is facilitated by promoter tethering and nuclear import of class IIa histone deacetylases.
Biochim. Biophys. Acta
PUBLISHED: 01-28-2014
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Aberrant expression levels of transcriptional regulators result in alterations in transcriptional control. STAF65? is a structural subunit of the GCN5 transcriptional co-activator complex. Reports showed that STAF65? is highly expressed in several human cancer cells, but the consequences of this aberrant expression pattern remain elusive. Here, we show that the STAF65? protein is highly expressed in lung adenocarcinoma patients and high levels of STAF65? correlate with poor prognosis. High levels of STAF65? cause repression of the c-Myc oncogene through physical association with transcription factor YY1 and co-repressors HDACs. Physical interactions between STAF65? and class IIa HDACs facilitate nuclear enrichment and regulate the assembly of HDAC complexes. Moreover, SUMOylation of STAF65? is necessary for maintaining the co-repressor complex containing YY1 and class IIa HDACs at the promoter. Our findings reveal a distinct role of STAF65? in nuclear import, transcriptional repression, and cell cycle regulation at high levels of expression, which is associated with poor clinical outcomes of lung adenocarcinoma.
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Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3.
Chem. Biol. Interact.
PUBLISHED: 01-28-2014
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The potential use of low-dose chemotherapy has been appealing because lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of paclitaxel, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic and possess the capability of activating additional apoptotic signals may provide a rational molecular basis for novel chemotherapeutic strategies. Luteolin, a natural flavone, possesses multiple biological activities, including anti-tumor potential. In the present study, the effects of concomitant administration of luteolin and paclitaxel were investigated in human breast cancer MDA-MB-231 cells. Luteolin alone demonstrated an anti-proliferative effect. Co-administration of luteolin and paclitaxel resulted in an increase in apoptosis compared with the treatment of paclitaxel alone as evidenced by the results of a diamidino-2-phenylindole (DAPI) stain and Annexin-V-based assay. Moreover, immunoblotting analysis also showed that the co-administration of luteolin and paclitaxel activated caspase-8 and caspase-3 and increased the expression of Fas. Furthermore, the increased expression of Fas due to co-administration was shown to be due to the blocking of signal transducer and activator of transcription 3 (STAT3). Finally, combination therapy with luteolin and paclitaxel significantly reduced tumor size and tumor weight in an orthotopic tumor model of MDA-MB-231 cells in nude mice. These results suggest that the luteolin-paclitaxel combination could be a novel strategy for the treatment of breast cancer.
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Case study of the Asian dust and pollutant event in spring 2006: source, transport, and contribution to Taiwan.
Sci. Total Environ.
PUBLISHED: 01-19-2014
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Surface measurements and a regional dust model were used to analyze the source, transport, and contribution of a dust event transporting with aerosol pollutant over Taiwan from 16 to 19 March, 2006. During the event, the hourly aerosol concentrations reached close to 400 ?g m(-3) in northern Taiwan, and approximately 300 ?g m(-3) in other areas of the island. Trajectory and regional dust models show that the dust event originated in eastern Mongolia and northern China, and the dust layer can descend from 2 to 3 km in the source area to below 1.5 km over Taiwan. On the other hand, model results show that pollution was transported near the surface from coastal China to Taiwan. During this dust event, polluted aerosol was first observed over northern Taiwan right after a frontal passage, and the concentration was strongly enhanced following the passage of the light rainfall 12h later. The descent of dusty air from the free troposphere lagged the arrival of polluted air by 7h, and was partially mixed with polluted aerosol when the transport decelerated over Taiwan. During the event, dust particles accounted for up to 60% of observed particulate matter less than 10 ?m (PM10) over Taiwan, but decreased to less than 35% for particulate matter less than 2.5 ?m (PM2.5) over most areas of the island. On the other hand, the long-range transport of non-dust aerosols, mainly anthropogenic pollutants, accounted for close to 30% of observed PM10 concentration in northern and western Taiwan prior to dust arrival, and the contribution of PM2.5 increased to close to 40% over the same areas. Local emission of aerosols accounted for less than 25% of PM10 concentrations in northern Taiwan, but was about 60% for PM2.5 in central and southern Taiwan because these areas are less influenced by long-range transport.
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Aesthetic and sensory reconstruction of finger pulp defects using free toe flaps.
Aesthetic Plast Surg
PUBLISHED: 01-18-2014
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This study illustrates aesthetic and sensory reconstruction of finger pulp defects with free toe flaps from the lateral aspect of the great toe or the medial aspect of the second toe.
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Iridal-type triterpenoids with neuroprotective activities from Iris tectorum.
J. Nat. Prod.
PUBLISHED: 01-16-2014
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Six novel iridal-type triterpenoids with a previously unreported 3,6-dihydro-2H-pyran moiety, named spirioiridotectals A-F (1-6), were isolated from the ethanol extract of the rhizomes of Iris tectorum. Their structures were elucidated on the basis of extensive spectroscopic analysis. Furthermore, in in vitro bioactivity assays, compounds 1, 2, and 6 exhibited neuroprotective activities against serum-deprivation-induced PC12 cell damage.
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CDKN1A-mediated responsiveness of MLL-AF4-positive acute lymphoblastic leukemia to Aurora kinase-A inhibitors.
Int. J. Cancer
PUBLISHED: 01-13-2014
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Overexpression of Aurora kinases is largely observed in many cancers, including hematologic malignancies. In this study, we investigated the effects and molecular mechanisms of Aurora kinase inhibitors in acute lymphoblastic leukemia (ALL). Western blot analysis showed that both Aurora-A and Aurora-B are overexpressed in ALL cell lines and primary ALL cells. Both VE-465 and VX-680 effectively inhibited Aurora kinase activities in nine ALL cell lines, which exhibited different susceptibilities to the inhibitors. Cells sensitive to Aurora kinase inhibitors underwent apoptosis at an IC50 of ?10-30 nM and displayed a phenotype of Aurora-A inhibition, whereas cells resistant to Aurora kinase inhibitors (with an IC50 more than 10 ?M) accumulated polyploidy, which may have resulted from Aurora-B inhibition. Drug susceptibility of ALL cell lines was not correlated with the expression level or activation status of Aurora kinases. Interestingly, RS4;11 and MV4;11 cells, which contain the MLL-AF4 gene, were both sensitive to Aurora kinase-A inhibitors treatment. Complementary DNA (cDNA) microarray analysis suggested that CDKN1A might govern the drug responsiveness of ALL cell lines in a TP53-independent manner. Most importantly, primary ALL cells with MLL-AF4 and CDKN1A expression were sensitive to Aurora kinase inhibitors. Our study suggests CDKN1A could be a potential biomarker in determining the drug responsiveness of Aurora kinase inhibitors in ALL, particularly in MLL-AF4-positive patients.
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Stemness and transdifferentiation of adipose-derived stem cells using L-ascorbic acid 2-phosphate-induced cell sheet formation.
Biomaterials
PUBLISHED: 01-08-2014
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Cell sheet technology has emerged as an important tissue engineering approach. Adipose-derived stem cells (ASCs) have valuable applications in regenerative medicine, but their stemness and differentiation capabilities in the cell sheet format have not been well investigated. In this study, we found that l-ascorbate 2-phosphate (A2-P), a stable form of ascorbic acid, significantly enhanced ASC proliferation and induced ASC sheet fabrication in 7 days with abundant extracellular matrix deposition. Importantly, A2-P treatment significantly enhanced expression of pluripotent markers Sox-2, Oct-4 and Nanog, but treating ASCs with antioxidants other than A2-P revealed no stemness enhancement. Moreover, ASC treatment with A2-P and a collagen synthesis inhibitor, L-2-azetidine carboxylic acid or cis-4-hydroxy-d-proline, significantly inhibited the A2-P-enhanced expression of stemness markers. These findings demonstrated that A2-P enhances stemness of ASCs through collagen synthesis and cell sheet formation. We also showed that A2-P-stimulated collagen synthesis in ASCs may be mediated through ERK1/2 pathway. By culturing the ASC sheets in proper induction media, ASC transdifferentiation capabilities into neuron and hepatocyte-like cells were significantly enhanced after cell sheet formation, while adipogenic and osteogenic differentiation capacities were still maintained. Using a murine model of healing-impaired cutaneous wound, faster wound healing was noted in the group that received ASC sheet treatment, and we observed significantly more engrafted ASCs with evidence of differentiation toward endothelial and epidermal lineages in the cutaneous wound tissue. Therefore, A2-P-mediated ASC sheet formation enhanced ASC stemness and transdifferentiation capabilities, thereby representing a promising approach for applications in regenerative medicine.
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Trajectories in functional recovery for patients receiving inpatient rehabilitation for unilateral hip or knee replacement.
Arch Gerontol Geriatr
PUBLISHED: 01-06-2014
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The purpose of this study was to explore trajectories of recovery in patients with lower extremity joint replacements receiving post-acute rehabilitation. A retrospective cohort design was used to examine data from the Uniform Data System for Medical Rehabilitation (UDSMR®) for 7434 patients with total knee replacement (TKR) and 4765 patients with total hip replacement (THR) who received rehabilitation from 2008 to 2010. Functional Independence Measure (FIM)™ instrument ratings were obtained at admission, discharge, and 80-180 days after discharge. Random coefficient regression analyses using linear mixed models were used to estimate mean ratings for items within the four motor subscales (self-care, sphincter control, transfers, and locomotion) and the cognitive domain of the FIM instrument. Mean improvements at discharge for motor items ranged from 1.16 (95% confidence interval [CI]: 1.14, 1.19) to 2.69 (95% CI: 2.66, 2.71) points for sphincter control and locomotion, respectively. At follow-up mean motor improvements ranged from 2.17 (95% CI: 2.15, 2.20) to 4.06 (95% CI: 4.03, 4.06) points for sphincter control and locomotion, respectively. FIM cognition yielded smaller improvements: discharge=0.47 (95% CI: 0.46, 0.48); follow-up=0.83 (95% CI: 0.81, 0.84). Persons who were younger, female, non-Hispanic white, unmarried, with fewer comorbid conditions, and who received a TKR demonstrated slightly higher functional motor ratings. Overall, patients with unilateral knee or hip replacement experienced substantial improvement in motor functioning both during and up to six months following inpatient rehabilitation.
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Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis.
Acta Pharmacol. Sin.
PUBLISHED: 01-02-2014
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To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects.
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Polygalasaponin F against rotenone-induced apoptosis in PC12 cells via mitochondria protection pathway.
J Asian Nat Prod Res
PUBLISHED: 01-02-2014
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To investigate the protective effect and the underlying mechanism of polygalasaponin F (PS-F) against rotenone-induced PC12 cells, the cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The cell apoptosis rate was analyzed using flow cytometry. The reactive oxygen species was examined using 2',7'-dichlorofluorescin diacetate, and the adenosine triphosphate depletion was examined using a luciferase-coupled quantification assay. JC-1 staining was used to detect the mitochondrial membrane potential. Western blotting analysis was used to determine cytochrome c, p53, Bax, Bcl-2, and caspase-3. Treatment of PC12 cells with rotenone (1-10 ?mol/l) significantly reduced the cell viability in a concentration-dependent manner. Treatment with PS-F (0.1, 1, and 10 ?mol/l) increased the viability of rotenone-induced PC12 cells, decreased rotenone-induced apoptosis, restored rotenone-induced mitochondrial dysfunction, and suppressed rotenone-induced protein expression. PS-F showed a dose-dependent manner in all the treatments. PS-F protects PC12 cells against rotenone-induced apoptosis via ameliorating the mitochondrial dysfunction. Thus, PS-F may be a potential bioactive compound for the treatment of Parkinson's disease.
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Color-tunable mixed photoluminescence emission from Alq3 organic layer in metal-Alq3-metal surface plasmon structure.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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This work reports the color-tunable mixed photoluminescence (PL) emission from an Alq3 organic layer in an Au-Alq3-Au plasmonic structure through the combination of organic fluorescence emission and another form of emission that is enabled by the surface plasmons in the plasmonic structure. The emission wavelength of the latter depends on the Alq3 thickness and can be tuned within the Alq3 fluorescent spectra. Therefore, a two-color broadband, color-tunable mixed PL structure was obtained. Obvious changes in the Commission Internationale d'Eclairage (CIE) coordinates and the corresponding emission colors of Au-Alq3-Au samples clearly varied with the Alq3 thickness (90, 130, and 156 nm).
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Nigrostriatal dynein changes in A53T alpha-synuclein transgenic mice.
F1000Res
PUBLISHED: 01-01-2014
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The accumulation of misfolded a-synuclein is mechanistically linked to neurodegeneration in Parkinson's disease (PD) and other alpha-synucleinopathies. However, how alpha-synuclein causes neurodegeneration is unresolved. Several studies have supported the involvement of dynein, the major motor for retrograde axonal transport in alpha-synuclein-dependent neurodegeneration, especially in the nigrostriatal system. Therefore, we examined the nigrostriatal dyneins in transgenic mice that overexpress human A53T alpha-synuclein and recapitulate key features of a PD-like neuronal synucleinopathy. Age-matched nontransgenic littermates were used as controls. The results demonstrated that the protein level of dynein was decreased in the striatum, whereas it was elevated in the substantia nigra. Double immunostaining results revealed that the reduction in dynein level was associated with aggregation of A53T a-synuclein in the striatum. Furthermore, we performed a quantitative analysis of motor behaviors in A53T alpha-synuclein transgenic mice and controls using a modified open field test. We demonstrated that the protein level of dynein in the striatum was significantly correlated with the motor behaviors. Together, our data indicate that dynein changes in the nigrostriatal system of A53T alpha-synuclein transgenic mice may contribute to their severe movement disorder.
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Enhanced plasmonic resonance energy transfer in mesoporous silica-encased gold nanorod for two-photon-activated photodynamic therapy.
Theranostics
PUBLISHED: 01-01-2014
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The unique optical properties of gold nanorods (GNRs) have recently drawn considerable interest from those working in in vivo biomolecular sensing and bioimaging. Especially appealing in these applications is the plasmon-enhanced photoluminescence of GNRs induced by two-photon excitation at infrared wavelengths, owing to the significant penetration depth of infrared light in tissue. Unfortunately, many studies have also shown that often the intensity of pulsed coherent irradiation of GNRs needed results in irreversible deformation of GNRs, greatly reducing their two-photon luminescence (TPL) emission intensity. In this work we report the design, synthesis, and evaluation of mesoporous silica-encased gold nanorods (MS-GNRs) that incorporate photosensitizers (PSs) for two-photon-activated photodynamic therapy (TPA-PDT). The PSs, doped into the nano-channels of the mesoporous silica shell, can be efficiently excited via intra-particle plasmonic resonance energy transfer from the encased two-photon excited gold nanorod and further generates cytotoxic singlet oxygen for cancer eradication. In addition, due to the mechanical support provided by encapsulating mesoporous silica matrix against thermal deformation, the two-photon luminescence stability of GNRs was significantly improved; after 100 seconds of 800 nm repetitive laser pulse with the 30 times higher than average power for imaging acquisition, MS-GNR luminescence intensity exhibited ~260% better resistance to deformation than that of the uncoated gold nanorods. These results strongly suggest that MS-GNRs with embedded PSs might provide a promising photodynamic therapy for the treatment of deeply situated cancers via plasmonic resonance energy transfer.
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[Mifepristone repairs alteration of learning and memory abilities in rat model of depression].
Yao Xue Xue Bao
PUBLISHED: 11-06-2013
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This study is to investigate the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression. In the present study, a 35-day rat chronic unpredictable stress (CUS) model was used to observe both depression-like behaviors with sucrose preference test and open-field test and learning and memory-associated behaviors with Morris water maze test. A total of 45 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM). Animals in CM group were first exposed to CUS for 14 days, and then were administered with 50 mg x kg(-1) x d(-1) of mifepristone with continued CUS procedure. Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT). Nissl staining was used to observe the structure of hippocampus. The results demonstrated that CUS exposure induced both depressive-like and learning and memory-associated behaviors and these deficits were reversed by mifepristone. Compared to CON group, the concentration of plasma CORT increased significantly in CUS group. CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect. Together, the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.
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[Oil of Piper longum unsaponifiable matter prevents cholesterol gallstone formation].
Yao Xue Xue Bao
PUBLISHED: 10-19-2013
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To observe the effect of various doses of oil of Piper longum unsaponifiable matter (OPUM) to cholesterol gallstones in experimental mice. C57BL/6 mice (n = 60) were randomly divided into 6 groups: control group, model group, OPUM (15, 30 and 60 mg x kg(-1)) group and ursodeoxycholic acid (UDCA, 60 mg x kg(-1)) group, administered for 10 weeks. The level of serum lipid and liver function enzymes were tested. The gallbladder was removed and bile was obtained by centrifugation. Next, the levels of the bile total cholesterol (TC), phospholipid (PL) and bile acid (TBA) were measured. The indicators of lipid peroxidation were determined and cholesterol saturation index (CSI) was calculated. The liver histological changes were observed by HE staining. The results showed that serum TC, TG (triglycerides) and AST (aspartate transaminase) contents, gallbladder cholesterol crystallization and CSI increased significantly (P < 0.05). In addition, the activity of SOD decreased significantly and MDA content increased significantly in liver (P < 0.05). HE staining results showed that the hepatic cord disorder and intracellular lipid droplets increased significantly. All results indicate that lithogenic diet lead to the formation of cholesterol gallstones. In OPUM (30 and 60 mg x kg(-1)) group, serum TC, TG and AST content, gallbladder cholesterol crystallization and CSI decreased significantly, the activity of SOD increased significantly and MDA content decreased significantly. HE staining results showed that OPUM can improve the morphology of liver cell, reduce the degree of hepatic cord disorders and restore the cell morphology close to normal. The cause of OPUM prevents cholesterol gallstone formation maybe due to protect the integrity of the liver cells, lower CSI, and reduce cholesterol crystal formation and hence prevent cholesterol gallstone formation.
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Treatment of distal fingertip degloving injuries using a cross-finger flap based on the dorsal branch of the proper digital artery at the middle phalanx.
J Reconstr Microsurg
PUBLISHED: 09-20-2013
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This study reports our experience with reconstruction of distal fingertip degloving injuries using a single cross-finger flap based on the dorsal branch of the proper digital artery at the middle phalanx. From January 2009 to October 2011, 18 patients (18 fingers) presented with distal fingertip degloving injuries and were treated with this technique. The mean size of the soft tissue defects was 4.5 cm in length and 2.0 cm in width. The mean size of the cross-finger flaps was 4.7 × 2.1 cm. In the series, all flaps survived completely. No complication was reported, and no further flap debunking procedure was required. At the mean follow-up period of 20.5 months (range, 12-48 mo), the mean static two-point discrimination was 6.3 mm (range, 5-9 mm) of the reconstructed finger pulp. The total range of active motion of the proximal and the distal interphalangeal joints of the donor fingers were 105 and 77.4 degrees, respectively. The cross-finger flap based on the dorsal branch of the proper digital artery at the middle phalanx is a reliable and simple method in reconstruction of distal degloving injuries of the finger.
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[Death/survival signaling pathways in cerebral ischemia and the developing therapeutic strategies].
Sheng Li Ke Xue Jin Zhan
PUBLISHED: 09-14-2013
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In an aging society, the incidence of brain ischemia increases dramatically. Despite progress in pathophysiology mechanisms, the medical therapy for brain ischemia has not been satisfactory. Recanalization using tissue plasminogen activator only modestly improves patient outcome, and inhibiting excitotoxicity has shown no clinical benefit. Both do not provide an adequate time window for effective stroke therapy in clinical practice. A more reasonable therapeutic window, and hence a greater potential for clinical success, is likely to be attained by placing emphasis on ameliorating the effects of the synergistic processes of programmed cell death (PCD) that is active for hours to days after ischemia. It is necessary to identify molecular mediators of ischemic neuroprotection suitable for translation to human clinical trials. In this review, the mechanisms of cell death/survival signaling pathways after ischemia and the potential therapeutic targets will be discussed.
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Novel sesquiterpenoid glycosides and sesquiterpenes from the roots of Illicium henryi.
Planta Med.
PUBLISHED: 08-27-2013
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Seven new sesquiterpenoid glycosides, consisting of one thapsan-type (1), two capnellane-type (2 and 3), four floridanolide sesquiterpene glycosides (4-7), and one new azulene-type sesquiterpene (8), along with six known sesquiterpenes (9-14) were isolated from the roots of Illicium henryi. The structures of 1-8 were elucidated by extensive spectroscopic analyses and chemical methods. The absolute configurations of 1, 2, and 8 were determined based on Rh2(OCOCF3)4-induced CD, Mo2(OAc)4-induced CD data, and calculated electronic circular dichroism (ECD), respectively. Compound 1 was found to exhibit weak neurotoxicant activity.
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Short-term spheroid formation enhances the regenerative capacity of adipose-derived stem cells by promoting stemness, angiogenesis, and chemotaxis.
Stem Cells Transl Med
PUBLISHED: 07-11-2013
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Adipose-derived stem cells (ASCs) represent an important source of mesenchymal stem cells for clinical application. During in vitro culture, ASCs quickly lose the expression of transcription factors associated with pluripotency and self-renewal (Sox-2, Oct-4, and Nanog) and CXCR4, the key receptor responsible for stem cell homing. To enhance their therapeutic potential despite in vitro passages, we examined whether ASCs exhibit superior regenerative capacity by expanding them in monolayers following short-term spheroid formation. Spheroid-derived ASCs retained the expression pattern of cell surface markers and adipogenic/osteogenic differentiation capabilities of ASCs constantly cultured in monolayers. However, spheroid-derived ASCs exhibited higher expansion efficiency with less senescence. Moreover, spheroid-derived ASCs expressed significantly higher levels of pluripotency markers, CXCR4, and angiogenic growth factors. Enhanced in vitro migration, associated with the increased expression of matrix metalloproteinases (MMP-9 and MMP-13), was also observed in spheroid-derived ASCs. The enhanced migration and MMP expression could be inhibited by a CXCR4-specific peptide antagonist, AMD3100. Using a murine model with healing-impaired cutaneous wounds, we observed faster healing and enhanced angiogenesis in the wounds treated with spheroid-derived ASCs. Significantly more cellular engraftment of spheroid-derived ASCs in the cutaneous wound tissue was also noted, with evidence of ASC differentiation toward endothelial and epidermal lineages. These findings suggest that short-term spheroid formation of ASCs before monolayer culture enhances their properties of stemness, angiogenesis, and chemotaxis and thereby increases their regenerative potential for therapeutic use.
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IMM-H004, a novel courmarin derivative, protects against oxygen-and glucose-deprivation/restoration-induced apoptosis in PC12 cells.
Eur. J. Pharmacol.
PUBLISHED: 06-07-2013
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7-Hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a novel coumarin derivative synthesized in our laboratory. The purpose of the current study was to determine the neuroprotective effects of IMM-H004 on PC12 cells and its potential mechanism of action. PC12 cells were subject to oxygen and glucose deprivation (OGD) followed by the restoration of oxygen and glucose (R), which mimics ischemia and reperfusion in vivo. Cell viability was determined by MTT assay. DNA fragmentation was analyzed by DNA ladder. ROS and mitochondrial membrane potential were measured by fluorescent microscope and quantified by Image-Pro Express 6.0 software. ATP was measured by luciferin-luciferase assay. The activation of signal-regulated molecules was assessed by the Western blot analysis. OH formation was determined using the Electron Spin Resonance (ESR) trapping technique in combination with 5, 5-dimethyl-1-pyrroline-N-oxide. OGD/R reduced cell viability and induced cell apoptosis, which were both dose-dependently attenuated by IMM-H004. The accumulation of intracellular reactive oxygen species (ROS) and reduced mitochondrial membrane potential observed in PC12 cells treated with OGD/R, which switch on the mitochondrion-dependent apoptotic pathway, were reversed by IMM-H004. ATP production in OGD/R-treated PC12 cells was elevated by IMM-H004, which suggests that it restored the functions of the mitochondria. OGD/R-induced cytochrome c release from the mitochondria reduced the ratio of apoptotic proteins, Bcl-2/Bax, and induced caspase-3 activation and DNA fragmentation. These changes were significantly inhibited by IMM-H004. IMM-H004 also significantly inhibited OH formation, determined by electron spin resonance, which indicates that it is a potent free-radical scavenger. This study has demonstrated that IMM-H004 protects PC12 cells against OGD/R-induced apoptosis, at least in part, by scavenging excessive ROS and inhibiting the mitochondrion-dependent apoptotic pathway.
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The nuclear accumulation of alpha-synuclein is mediated by importin alpha and promotes neurotoxicity by accelerating the cell cycle.
Neuropharmacology
PUBLISHED: 04-12-2013
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?-Synuclein (?-syn), a 14 kDa pre-synaptic protein, is widely involved in the Parkinsons disease (PD) pathogenesis. Recent studies have shown that the nuclear accumulation of ?-syn might have a toxic effect. The main purpose of the present study was to explore which amino acid residues in ?-syn are associated with its nuclear accumulation, the molecule(s) mediated the nuclear import of ?-syn, and the role of ?-syn accumulated in the nucleus. It has been noted that the nuclear import of ?-syn may be mediated by importin ? and that both the amino acid residues 1-60 and 103-140 of ?-syn were indispensable for its nuclear import. After imported into the nucleus, the accumulated ?-syn played a toxic role in both the PC12 cells and the C57 mice. Furthermore, ?-syn-nuclear localization signal-injected mice showed behavioral symptoms associated with PD. Further studies performed in vitro showed that the toxicity of ?-syn in the nucleus might be due to an interference of the cell cycle. Thus, it can be concluded that ?-syn can accumulate in nucleus, which is mediated by importin ?, and promote neurotoxicity by accelerating the cell cycle. This article is part of a Special Issue entitled Neurodegenerative Disorders.
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Patterns of executive dysfunction in amnestic mild cognitive impairment.
Int Psychogeriatr
PUBLISHED: 04-11-2013
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Executive dysfunction is not uncommon in patients with amnestic mild cognitive impairment (aMCI). This study aimed to investigate the applicability of executive function tests (EFTs) in aMCI as an aid in establishing the diagnosis of multi-domain MCI.
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Claulansine F promotes neuritogenesis in PC12 cells via the ERK signaling pathway.
Acta Pharmacol. Sin.
PUBLISHED: 03-29-2013
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Aim:To study the effects of Claulansine F (Clau F), a carbazole alkaloid isolated from the stem of Clausena lansium (Lour) Skeels, on neuritogenesis of PC12 cells, and to elucidate the mechanism of action.Methods:Neuritogenesis of PC12 cells was quantified under an inverted microscope. Expression of the neurite outgrowth marker GAP-43 was detected using immunofluorescence. GAP-43 transcription was measured using RT-PCR. Cell viability was evaluated with MTT assay. The levels of phosphor-ERK1/2, phosphor-CREB, phosphor-AKT and acetylate-p53 in the cells were examined using Western blotting analyses.Results:Clau F (10-100 ?mol/L) significantly increased the percentage of PC12 cells bearing neurites. Clau F markedly increased the expression of GAP-43 in the cells. The efficiency of Clau F (10 ?mol/L) in increasing neuritogenesis and GAP-43 expression was comparable to that of nerve growth factor (50 ng/mL). In addition, Clau F completely blocked the proliferation of PC12 cells within 7 d of incubation, whereas it did not cause cell death in cultured rat cortical neurons. Treatment of PC12 cells with Clau F activated both ERK and AKT signaling pathways. Co-treatment of PC12 cells with the specific ERK inhibitor PD98059, but not the specific PI3K inhibitor LY294002, blocked Clau F-induced neuritogenesis and GAP-43 upregulation.Conclusion:Clau F promotes neuritogenesis in PC12 cells specifically via activation of the ERK signaling pathway.
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Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3?/tau signaling pathway and the A? formation prevention in rats.
Eur. J. Pharmacol.
PUBLISHED: 03-22-2013
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Ginsenoside Rg1, one of the major active ingredients isolated from Panax Ginseng, has been shown notable neuroprotective effects in memory impairment animals. However, the role of ginsenoside Rg1 on cognition capacity damaged by neurofibrillary tangles (NFTs) is still poorly understood, and the underlying mechanism remain to be fully elucidated. Okadaic acid (OKA), a potent phosphatase inhibitor, often apply to imitate Alzheimers disease-like symptom damaged by neurofibrillary tangles, was used to investigate the effects of ginsenoside Rg1 on memory impairment and the related mechanisms in Sprague Dawley (SD) rats. The anti-dementic drug donepezil was used as a positive contrast. The results showed that OKA intracerebroventricular (i.c.v.) injection induced memory impairment, including changes in the ability of orientation navigate, spatial probe and relearning memory in behavioral test of Morris water maze (MWM). However, treatment with Rg1 and donepezil remarkably alleviated these changes. Also OKA treated rats showed memory impairment including increasing of phospho-tau, decreasing of phospho-GSK3? and the formation of ?-amyloid in special brain regions, which were reversed by Rg1 (20 mg/kg) and donepezil (1 mg/kg) administration. All these indicating that ginsenoside Rg1 protects rats against OKA-induced neurotoxicity. The possible neuroprotective mechanism may be that Rg1 decreases OKA-induced memory impairment through GSK3?/tau signaling pathway and/or attenuating A? formation. Thus, these studies indicate that ginsenoside Rg1 might be a potential preventive drug for Alzheimers disease.
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A modified free chimeric osteocutaneous fibular flap design for head and neck reconstruction: experience on a series of 10 cases.
Microsurgery
PUBLISHED: 03-12-2013
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We have previously described a modified chimeric fibular osteocutaneous flap design based on a combination of a traditional fibular flap and a peroneal artery perforator fasciocutaneous flap for mandible and adjacent soft tissue reconstruction. The purpose of this article is to share our experience with a larger case series utilizing this new technique for mandible and adjacent soft tissue reconstruction after cancer wide excision surgery and a more detailed description on these flaps harvesting procedures.
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Phenethyl isothiocyanate suppresses EGF-stimulated SAS human oral squamous carcinoma cell invasion by targeting EGF receptor signaling.
Int. J. Oncol.
PUBLISHED: 03-03-2013
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Phenethyl isothiocyanate (PEITC) is a natural compound that is involved in chemoprevention as well as inhibition of cell growth and induction of apoptosis in several types of cancer cells. Previous studies have revealed that PEITC suppresses the invasion of AGS gastric and HT-29 colorectal cancer cells. However, the effects of PEITC on the metastasis of SAS oral cancer cells remain to be determined. Our results showed that PEITC treatment inhibited the invasion of EGF-stimulated SAS cells in a concentration-dependent manner, but appeared not to affect the cell viability. The expression and enzymatic activities of matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) were suppressed by PEITC. Concomitantly, we observed an increase in the protein expression of both tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 (TIMP-2) in treated cells. Furthermore, PEITC treatments decreased the protein phosphorylation of epidermal growth factor receptor (EGFR) and downstream signaling proteins including PDK1, PI3K (p85), AKT, phosphorylated IKK and I?B to inactivate NF-?B for the suppression of MMP-2 and MMP-9 expression. In addition, PEITC can trigger the MAPK signaling pathway through the increase in phosphorylated p38, JNK and ERK in treated cells. Our data indicate that PEITC is able to inhibit the invasion of EGF-stimulated SAS oral cancer cells by targeting EGFR and its downstream signaling molecules and finally lead to the reduced expression and enzymatic activities of both MMP-2 and MMP-9. These results suggest that PEITC is promising for the therapy of oral cancer metastasis.
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Real-time tracheal ultrasonography for confirmation of endotracheal tube placement during cardiopulmonary resuscitation.
Resuscitation
PUBLISHED: 02-26-2013
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This study aimed to evaluate the accuracy of tracheal ultrasonography for assessing endotracheal tube position during cardiopulmonary resuscitation (CPR).
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Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells.
Oncol. Rep.
PUBLISHED: 02-26-2013
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Kaempferol is a natural flavonoid that possesses anti-proliferative and apoptosis-inducing activities in several cancer cell lines. In the present study, we investigated the anti-metastatic activity of kaempferol and its molecular mechanism(s) of action in human osteosarcoma cells. Kaempferol displayed inhibitory effects on the invasion and adhesion of U-2 osteosarcoma (OS) cells in a concentration-dependent manner by Matrigel Transwell assay and cell adhesion assay. Kaempferol also inhibited the migration of U-2 OS cells in a concentration-dependent manner at different treatment time points by wound-healing assay. Additional experiments showed that kaempferol treatment reduced the enzymatic activities and protein levels of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen activator (uPA) by gelatin and casein-plasminogen zymography assays and western blot analyses. Kaempferol also downregulated the mRNA levels of MMP-2 and MMP-9 by quantitative PCR analyses. Furthermore, kaempferol was able to reduce the protein phosphorylation of ERK, p38 and JNK by western blotting. By electrophoretic mobility-shift assay (EMSA), we demonstrated that kaempferol decreased the DNA binding activity of AP-1, an action likely to result in the reduced expression of MMP-2, MMP-9 and uPA. Collectively, our data showed that kaempferol attenuated the MAPK signaling pathways including ERK, JNK and p38 and resulted in the decreased DNA binding ability of AP-1, and hence, the downregulation in the expression and enzymatic activities of MMP-2, MMP-9 and uPA, contributing to the inhibition of metastasis of U-2 OS cells. Our results suggest a potential role of kaempferol in the therapy of tumor metastasis of OS.
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Rotenone could activate microglia through NF?B associated pathway.
Neurochem. Res.
PUBLISHED: 02-22-2013
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Parkinsons disease (PD) is a common neurodegenerative disease, and its etiology remains obscure. Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in increasing the risk of developing PD and inflammation is the early incident during the process of PD. In this study, we measure the pro-inflammatory cytokines by enzyme-linked immunosorbnent assay and RT-PCR methods; analyze the reactive oxygen species by DCFH-DA; detected nuclear factor ?B (NF?B) translocation by western blot and immunofluorescence methods; and analyze the phosphorylation of mitogen-activated protein (MAP) kinase and protein level of Nurr1 by western blot. Results showed that rotenone could induce tumor neurosis factor ? (TNF?) and interleukin 1? (IL-1?) release from BV-2 cells, enhance TNF? and IL-1? mRNA levels in substantia nigra lesioned by rotenone; also, rotenone could increase the phosphorylation of inhibitor of ?B (I?B), extracellular regulated protein kinase , c-Jun N-terminal kinase, p38 MAP kinases and promote p65 subunit of NF?B translocation to nuclear; at the same time, rotenone could decrease the protein level of Nurr1 in nuclear. So, rotenone exerted toxicity through activating microglia, and its mechanism might be associated with NF?B signal pathway.
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Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model.
J. Surg. Res.
PUBLISHED: 02-02-2013
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Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model.
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Detection of gray matter damage using brain MRI and SPECT in carbon monoxide intoxication: a comparison study with neuropsychological correlation.
Clin Nucl Med
PUBLISHED: 01-22-2013
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While lesion patterns in white matter have been extensively reported in the literature on carbon monoxide (CO) intoxication, reports on the effects on gray matter damage are less common. The aim of this study was to investigate regional damage patterns focusing on gray matter using (99m)Tc ethyl cysteinate dimer (ECD) brain single photon emission computed tomography (SPECT) and brain magnetic resonance imaging (MRI) with clinical correlation.
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Factors associated with use of emergency medical services in patients with acute stroke.
Am J Emerg Med
PUBLISHED: 01-21-2013
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The aim of this study was to investigate the factors associated with use of emergency medical services (EMS) in patients with acute stroke.
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Separation and structure elucidation of a new homoflavanol derivative from Pteridium aquilinum (L.) Kuhn.
Nat. Prod. Res.
PUBLISHED: 01-21-2013
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A novel homoflavanol derivative (1) with an unprecedented skeleton, as well as two known flavonoids kaempferol (2) and quercetin (3), was isolated from the plant Pteridium aquilinum (L.) Kuhn, and the structure and relative stereochemistry of the new compound (1) were elucidated on the basis of spectroscopic data.
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Conditionally ablated Pten in prostate basal cells promotes basal-to-luminal differentiation and causes invasive prostate cancer in mice.
Am. J. Pathol.
PUBLISHED: 01-09-2013
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Prostate glands comprise two major epithelial cell types: luminal and basal. Luminal cells have long been considered the cellular origin of prostate cancer (CaP). However, recent evidence from a prostate regeneration assay suggests that prostate basal cells can also give rise to CaP. Here, we characterize Pten-deficient prostate lesions arising from keratin 5-expressing basal cells in a temporally controlled system in mice. Pten-deficient prostate lesions arising from basal cells exhibited luminal phenotypes with higher invasiveness, and the cell fate of Pten-deficient basal cells was traced to neoplastic luminal cells. After temporally ablating Pten in keratin 8-expressing luminal cells, luminal-derived Pten-deficient prostate tumors exhibited slower disease progression, compared with basal-derived tumors, within 13 weeks after Pten ablation. Cellular proliferation was significantly increased in basal-derived versus luminal-derived Pten-deficient prostate lesions. Increased tumor invasion into the smooth muscle layer and aberrantly regulated aggressive signatures (Smad4 and Spp1) were identified exclusively in basal-derived Pten-deficient lesions. Interestingly, p63-expressing cells, which represent basal stem and progenitor cells of basal-derived Pten-deficient prostate lesions, were significantly increased, relative to cells of the luminal-derived prostate lesion. Furthermore, castration did not suppress cellular proliferation of either basal-derived or luminal-derived Pten-deficient prostate tumors. Taken together, our data suggest that, although prostate malignancy can originate from both basal and luminal populations, these two populations differ in aggressive potential.
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Supercharged reversed gastric tube technique: a microvascular anastomosis procedure for pharyngo-oesophageal reconstruction after total laryngopharyngo-oesophagectomy.
Eur J Cardiothorac Surg
PUBLISHED: 01-07-2013
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This study aimed to assess the supercharged reversed gastric tube (RGT) technique as a method for pharyngo-oesophageal reconstruction after total laryngopharyngo-oesophagectomy (TLPE).
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Study on the dynamic changes in synaptic vesicle-associated protein and axonal transport protein combined with LPS neuroinflammation model.
ISRN Neurol
PUBLISHED: 01-01-2013
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Microglia activation is the major component of inflammation that constitutes the characteristic of neurodegenerative disease. A large amount of researches have demonstrated that inflammation involved in the pathogenesis of PD process activated microglia acting on the neurons through the release of a variety of inflammatory factors. However, the molecular mechanism underlying how it does work on neurons is still unclear. Here, we show that intracerebral injections of LPS induced Parkinsons disease pathology in C57BL/6J mice. Furthermore, study on the dynamic changes in Synaptic vesicle-associated protein and axonal transport Protein in this process. The results indicated that after administration of LPS in the brain, the inflammatory levels of TNF- ? and IL-1 ? both are elevated, and have a time-dependent.
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Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats.
Neuropsychopharmacology
PUBLISHED: 12-21-2011
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Growing evidence has implicated glial anomalies in the pathophysiology of major depression disorder (MDD). Gap junctional communication is a main determinant of astrocytic function. However, it is unclear whether gap junction dysfunction is involved in MDD development. This study investigates changes in the function of astrocyte gap junction occurring in the rat prefrontal cortex (PFC) after chronic unpredictable stress (CUS), a rodent model of depression. Animals exposed to CUS and showing behavioral deficits in sucrose preference test (SPT) and novelty suppressed feeding test (NSFT) exhibited significant decreases in diffusion of gap junction channel-permeable dye and expression of connexin 43 (Cx43), a major component of astrocyte gap junction, and abnormal gap junctional ultrastructure in the PFC. Furthermore, we analyzed the effects of typical antidepressants fluoxetine and duloxetine and glucocorticoid receptor (GR) antagonist mifepristone on CUS-induced gap junctional dysfunction and depressive-like behaviors. The cellular and behavioral alterations induced by CUS were reversed and/or blocked by treatment with typical antidepressants or mifepristone, indicating that the mechanism of their antidepressant action may involve the amelioration of gap junction dysfunction and the cellular changes may be related to GR activation. We then investigated the effects of pharmacological gap junction blockade in the PFC on depressive-like behaviors. The results demonstrate that carbenoxolone (CBX) infusions induced anhedonia in SPT, and anxiety in NSFT, and Cx43 mimetic peptides Gap27 and Gap26 also induced anhedonia, a core symptom of depression. Together, this study supports the hypothesis that gap junction dysfunction contributes to the pathophysiology of depression.
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Huperzine A derivative M3 protects PC12 cells against sodium nitroprusside-induced apoptosis.
Acta Pharmacol. Sin.
PUBLISHED: 11-28-2011
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To investigate the effects of M3, a derivative of huperzine A, on the apoptosis induced by sodium nitroprusside (SNP) in PC12 cells.
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[Advances in the study of small molecule antagonists of chemokine receptors as anti-asthma agents].
Yao Xue Xue Bao
PUBLISHED: 11-10-2011
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Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.
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Crystal structures of the laminarinase catalytic domain from Thermotoga maritima MSB8 in complex with inhibitors: essential residues for ?-1,3- and ?-1,4-glucan selection.
J. Biol. Chem.
PUBLISHED: 11-07-2011
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Laminarinases hydrolyzing the ?-1,3-linkage of glucans play essential roles in microbial saccharide degradation. Here we report the crystal structures at 1.65-1.82 ? resolution of the catalytic domain of laminarinase from the thermophile Thermotoga maritima with various space groups in the ligand-free form or in the presence of inhibitors gluconolactone and cetyltrimethylammonium. Ligands were bound at the cleft of the active site near an enclosure formed by Trp-232 and a flexible GASIG loop. A closed configuration at the active site cleft was observed in some molecules. The loop flexibility in the enzyme may contribute to the regulation of endo- or exo-activity of the enzyme and a preference to release laminaritrioses in long chain carbohydrate hydrolysis. Glu-137 and Glu-132 are proposed to serve as the proton donor and nucleophile, respectively, in the retaining catalysis of hydrolyzation. Calcium ions in the crystallization media are found to accelerate crystal growth. Comparison of laminarinase and endoglucanase structures revealed the subtle difference of key residues in the active site for the selection of ?-1,3-glucan and ?-1,4-glucan substrates, respectively. Arg-85 may be pivotal to ?-1,3-glucan substrate selection. The similarity of the structures between the laminarinase catalytic domain and its carbohydrate-binding modules may have evolutionary relevance because of the similarities in their folds.
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[Avian diversity and bird strike risk at Fuyang Airport].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 10-20-2011
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From June 2008 to January 2010, a survey of avian communities was conducted in five habitats (grassland, farmland, town, wetland, and woodland) at Fuyang Airport and its surrounding areas, with the diversity indices in different seasons and different habitats analyzed. A total of 122 avian species belonging to 15 orders and 40 families were recorded. At Fuyang Airport, the avian species number was significantly higher in summer and autumn than in winter and spring, the avian density was the highest in autumn, and the Shannon diversity index and Pielou evenness index were the highest in summer. Among the five habitats at the Airport and its surrounding areas, woodland had the greatest avian species number and density, and the woodland, wetland, and farmland had higher Shannon diversity index than grassland and town. The most dangerous avian species to the airplanes at Fuyang Airport were Passer montanus, Pycnonotus sinensis, Hirundo rustica, Columba livia f. domestica, Pica pica, Streptopelia chinensis, and Sturnus cineraceu.
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C19, a C-terminal peptide of chemokine-like factor 1, protects the brain against focal brain ischemia in rats.
Neurosci. Lett.
PUBLISHED: 10-18-2011
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There has been accumulating evidence that chemokines play an important role in cerebral ischemia. Chemokines-like factor 1 (CKLF1), as a novel C-C chemokine, is upregulated in cerebral ischemia. In this study we examined the protective effect of C19, a C-terminal peptide of chemokine-like factor 1, in an animal model of cerebral ischemia. Adult rats were anesthetized with chloral hydrate. C19 was given intracerebroventricularly immediately after 60 min middle cerebral artery occlusion. Animals were examined for their neurological function, infarct size and water content at 24h after reperfusion. The result showed that C19 (0.1, 1, 10 or 50 ?g) significantly improved neurological function, decreased infarct size and water content in a dose-dependent manner. In contrast, application of C19 (50 ?g) showed no effect in normal rats. Taken together, our data suggest that C19 is protective against ischemic brain injury, and may be an ideal peptide drug for the treatment of cerebral ischemia.
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The influence of spheroid formation of human adipose-derived stem cells on chitosan films on stemness and differentiation capabilities.
Biomaterials
PUBLISHED: 10-11-2011
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Adipose-derived stem cells (ASCs) have valuable applications in regenerative medicine, but maintaining the stemness of ASCs during in vitro culture is still a challenging issue. In this study, human ASCs spontaneously formed three-dimensional spheroids on chitosan films. Most ASCs within the spheroid were viable, and the cells produced more extracellular molecules, like laminin and fibronectin. Comparing to monolayer culture, ASC spheroids also exhibited enhanced cell survival in serum deprivation condition. Although cell proliferation was inhibited in spheroids, ASCs readily migrated out and proliferated upon transferring spheroids to another adherent growth surface. Moreover, spheroid-derived ASCs exhibited higher expansion efficiency and colony-forming activity. Importantly, we demonstrated that spheroid formation of human ASCs on chitosan films induced significant upregulation of pluripotency marker genes (Sox-2, Oct-4 and Nanog). By culturing the ASC spheroids in proper induction media, we found that ASC differentiation capabilities were significantly enhanced after spheroid formation, including increased transdifferentiation efficiency into neuron and hepatocyte-like cells. In a nude mice model, we further showed a significantly higher cellular retention ratio of ASC spheroids after intramuscular injection of spheroids and dissociated ASCs. These results suggested that ASCs cultured as spheroids on chitosan films can increase their therapeutic potentials.
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Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against rotenone injury in PC12 cells.
Acta Pharmacol. Sin.
PUBLISHED: 10-03-2011
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To investigate the protective effect and underlying mechanisms of Bu-7, a flavonoid isolated from the leaves of Clausena lansium, against rotenone-induced injury in PC12 cells.
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Terpyridine platinum(II) complexes inhibit cysteine proteases by binding to active-site cysteine.
J. Biomol. Struct. Dyn.
PUBLISHED: 08-31-2011
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Platinum(II) complexes have been demonstrated to form covalent bonds with sulfur-donating ligands (in glutathione, metallothionein and other sulfur-containing biomolecules) or coordination bonds with nitrogen-donating ligands (such as histidine and guanine). To investigate how these compounds interact with cysteine proteases, we chose terpyridine platinum(II) (TP-Pt(II)) complexes as a model system. By using X-ray crystallography, we demonstrated that TP-Pt(II) formed a covalent bond with the catalytic cysteine residue in pyroglutamyl peptidase I. Moreover, by using MALDI (matrix-assisted laser desorption/ionization) and TOF-TOF (time of flight) mass spectrometry, we elucidated that the TP-Pt(II) complex formed a covalent bond with the active-site cysteine residue in two other types of cysteine protease. Taken together, the results unequivocally showed that TP-Pt(II) complexes can selectively bind to the active site of most cysteine proteases. Our findings here can be useful in the design of new anti-cancer, anti-parasite or anti-virus platinum(II) compounds.
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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.

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