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Find video protocols related to scientific articles indexed in Pubmed.
Siloxy Alkynes in Annulation Reactions.
Chem Rec
PUBLISHED: 08-29-2014
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Siloxy alkynes are a family of versatile species in organic synthesis. This account reviews the annulation reactions of siloxy alkynes for the synthesis of a variety of carbo- and heterocyclic products. With various dipolarophiles or dipolarophile-like reaction partners, siloxy alkynes are capable of forming small (three- to six-membered) rings. Recently, we have expanded the scope to the synthesis of medium- and large-ring lactones, enabled by the design of new amphoteric molecules as well as a new ring-expansion strategy. These annulation reactions provide not only practically useful syntheses of cyclic molecules, but also important understanding of the fundamental reactivity of siloxy alkynes.
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The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.
Nat. Biotechnol.
PUBLISHED: 08-24-2014
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The concordance of RNA-sequencing (RNA-seq) with microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed using a range of chemical treatment conditions. Here we use a comprehensive study design to generate Illumina RNA-seq and Affymetrix microarray data from the same liver samples of rats exposed in triplicate to varying degrees of perturbation by 27 chemicals representing multiple modes of action (MOAs). The cross-platform concordance in terms of differentially expressed genes (DEGs) or enriched pathways is linearly correlated with treatment effect size (R(2)?0.8). Furthermore, the concordance is also affected by transcript abundance and biological complexity of the MOA. RNA-seq outperforms microarray (93% versus 75%) in DEG verification as assessed by quantitative PCR, with the gain mainly due to its improved accuracy for low-abundance transcripts. Nonetheless, classifiers to predict MOAs perform similarly when developed using data from either platform. Therefore, the endpoint studied and its biological complexity, transcript abundance and the genomic application are important factors in transcriptomic research and for clinical and regulatory decision making.
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FOXA2 suppresses the metastasis of hepatocellular carcinoma partially through matrix metalloproteinase-9 inhibition.
Carcinogenesis
PUBLISHED: 08-20-2014
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The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues. Clinicopathological analysis revealed that reduced FOXA2 expression was correlated with aggressive characteristics (venous invasion, poor differentiation, high tumor node metastasis grade). FOXA2 level was even lower in portal vein tumor thrombus compared with primary tumor tissues and correlated with epithelial-mesenchymal transition in HCC cells. Overexpression of FOXA2 inhibited migration and invasion of Focus cells, whereas knockdown of FOXA2 in HepG2 showed the opposite effect. Moreover, upregulation of FOXA2 suppressed HCC metastasis to bone, brain and lung in two distinct mouse models. Finally, we proved that FOXA2 repressed the transcription of matrix metalloproteinase (MMP)-9 and exerted its antimetastasis effect partially through downregulation of MMP-9. In conclusion, our findings indicate that FOXA2 plays a critical role in HCC metastasis and may serve as a novel therapeutic target for HCC.
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A parametric study of nonlinear seismic response analysis of transmission line structures.
ScientificWorldJournal
PUBLISHED: 07-15-2014
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A parametric study of nonlinear seismic response analysis of transmission line structures subjected to earthquake loading is studied in this paper. The transmission lines are modeled by cable element which accounts for the nonlinearity of the cable based on a real project. Nonuniform ground motions are generated using a stochastic approach based on random vibration analysis. The effects of multicomponent ground motions, correlations among multicomponent ground motions, wave travel, coherency loss, and local site on the responses of the cables are investigated using nonlinear time history analysis method, respectively. The results show the multicomponent seismic excitations should be considered, but the correlations among multicomponent ground motions could be neglected. The wave passage effect has a significant influence on the responses of the cables. The change of the degree of coherency loss has little influence on the response of the cables, but the responses of the cables are affected significantly by the effect of coherency loss. The responses of the cables change little with the degree of the difference of site condition changing. The effect of multicomponent ground motions, wave passage, coherency loss, and local site should be considered for the seismic design of the transmission line structures.
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The effect analysis of strain rate on power transmission tower-line system under seismic excitation.
ScientificWorldJournal
PUBLISHED: 06-29-2014
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The effect analysis of strain rate on power transmission tower-line system under seismic excitation is studied in this paper. A three-dimensional finite element model of a transmission tower-line system is created based on a real project. Using theoretical analysis and numerical simulation, incremental dynamic analysis of the power transmission tower-line system is conducted to investigate the effect of strain rate on the nonlinear responses of the transmission tower and line. The results show that the effect of strain rate on the transmission tower generally decreases the maximum top displacements, but it would increase the maximum base shear forces, and thus it is necessary to consider the effect of strain rate on the seismic analysis of the transmission tower. The effect of strain rate could be ignored for the seismic analysis of the conductors and ground lines, but the responses of the ground lines considering strain rate effect are larger than those of the conductors. The results could provide a reference for the seismic design of the transmission tower-line system.
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Cryopreserved mouse fetal liver stromal cells treated with mitomycin C are able to support the growth of human embryonic stem cells.
Exp Ther Med
PUBLISHED: 06-23-2014
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An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70°C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 ?g/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 ?g/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at -70°C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70°C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70°C short-term or liquid nitrogen cryopreservation.
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[Partial pressure and diffusion flux of dissolved carbon dioxide in the mainstream and tributary of the central Three Gorges Reservoir in summer].
Huan Jing Ke Xue
PUBLISHED: 06-03-2014
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This study investigated the partial pressure of CO2 (pCO2) in the mainstream of the Three Gorges Reservoir and its tributary (Meixi River) in May 2013. Results showed that pCO2 in the surface water of the Meixi River and mainstream of the Three Gorges Reservoir was 6.8-7.5 Pa and 201.4-210.2 Pa, respectively. At the mixing area between the Meixi River and the mainstream of Changjiang, the lowest value of pCO2 in surface water was 53.5 Pa, and pCO2 gradually increased downwardly. Below 3 m in depth, pCO2 kept the stable value of around 210 Pa. Based on the calculation results, the emission flux of CO2 in the Meixi River and the mainstream of the central Three Gorges Reservoir was about -7.48 mmol x (m2 x d)(-1) and 39.58 mmol x (m2 x d)(-1), respectively. These results showed that the Meixi River is a sink for atmospheric CO2, and the mainstream of the Three Gorges Reservoir is a source for atmospheric CO2.
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Wnt5a promotes inflammatory responses via nuclear factor ?B (NF-?B) and mitogen-activated protein kinase (MAPK) pathways in human dental pulp cells.
J. Biol. Chem.
PUBLISHED: 06-02-2014
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Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-? stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-?, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/ chemokine production induced by TNF-?. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-?. However, no TNF-? and IL-1? was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-?B-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-?.
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Sophocarpine Attenuates Toll-like Receptor 4 in Steatotic Hepatocytes to Suppress Pro-inflammatory Cytokines Synthesis.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-30-2014
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Sophocarpine, a tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L, has been documented that it can suppress pro-inflammatory cytokines synthesis in alleviating non-alcoholic steatohepatitis (NASH) in vivo. TLR4 is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines. It has been reported that TLR4 is up-regulated in NAFLD and plays an important role in the pathogenesis of NASH. This study aimed to examine the changes of TLR4 and its signaling pathways in sophocarpine's anti-inflammatory process on experimental NASH in vitro.
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Nanofiber scaffolds for treatment of spinal cord injury.
Curr. Med. Chem.
PUBLISHED: 05-26-2014
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Spinal cord injury (SCI) is a common neurologic disorder that results in loss of sensory function and mobility. It is well documented that tissue engineering is a potential therapeutic strategy for treatment of SCI. In this connection, various biomaterials have been explored to meet the needs of SCI tissue engineering and these include natural materials, synthetic biodegradable polymers and synthetic non- degradable polymers. Nanofiber scaffolds are newly emerging biomaterials that have been widely utilized in tissue engineering recently. In comparison to the traditional biomaterials, nanofibers have advantages in topography and porosity, thus mimicking the naturally occurring extracellular matrix. Besides, they exhibit excellent biocompatibility with low immunogenicity, and furthermore they are endowed with properties that help to bridge the lesion cavity or gap, and serve as an effective delivery system for graft cells or therapeutic drugs. This review summarizes some of the unique properties of nanofiber scaffolds which are critical to their potential application in treatment of injured spinal cord.
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[Progress of researches on prevention and treatment of sports fatigue with moxibustion therapy].
Zhen Ci Yan Jiu
PUBLISHED: 05-14-2014
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Sports fatigue belongs to the category of functional deficiency-syndrome according to the theory of traditional Chinese medicine. The moxibustion therapy has a long history and possesses a definite therapeutic effect in the prevention and treatment of sports fatigue. In the present paper, the authors reviewed development of researches on the effects of moxibustion intervention in the prevention and treatment of sports fatigue in recent 5 years. Results of researches showed that moxibustion intervention can 1) eliminate free radicals and reduce oxidative damage; 2) increase energy (glycogen) supply to delay the production of fatigue; 3) raise serum testosterone level (relieve exercise-induced neuroendocrine disorder) and reduce post-sports fatigue; 4) raise the anaerobic exercise ability, reduce the accumulation of metabolic products in the body and strengthen the endurance capacity of the skeletal muscle; and 5) improve ischemic cardiac function, and suppress cardiomyocyte apopotosis, etc. However, we should further strengthen our investigations on the moxibustion therapy in the ancient classical literature and sum up academic thoughts of different academic schools in the successive dynasties, put emphasis on the large sample randomized controlled clinical trails, establish united treatment standards, etc., and provide much evidence for effectively treating sports fatigue in the future.
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Intravoxel incoherent motion MRI: emerging applications for nasopharyngeal carcinoma at the primary site.
Eur Radiol
PUBLISHED: 04-24-2014
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We compared pure molecular diffusion (D), perfusion-related diffusion (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) based on intravoxel incoherent motion (IVIM) theory in patients with nasopharyngeal carcinoma (NPC).
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Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest.
Neurol. Sci.
PUBLISHED: 04-23-2014
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Mild hypothermia is an effective therapeutic strategy to improve poor neurological outcomes in patients following cardiac arrest (CA). However, the underlying mechanism remains unclear. The aim of the study was to evaluate the effect of mild hypothermia on intracellular autophagy and mitophagy in hippocampal neurons in a rat model of CA. CA was induced in Sprague-Dawley (SD) rats by asphyxia for 5 min. After successful resuscitation, the surviving rats were randomly divided into two groups, the normothermia (NT) group and the hypothermia (HT) group. Mild hypothermia (32 °C) was induced following CA for 4 h, and animals were rewarmed at a rate of 0.5 °C/h. Neurologic deficit scores (NDS) were used to determine the status of neurological function. Cytoplasmic and mitochondrial protein from the hippocampus was extracted, and the expression of LC3B-II/I and Parkin were measured as markers of intracellular autophagy and mitophagy, respectively. Of the 60 rats that underwent CA, 44 were successfully resuscitated (73 %), and 33 survived until the end of the experiment (55 %). Mild hypothermia maintained eumorphism of nuclear and mitochondrial structures and significantly improved NDS (p < 0.05). Expression of LC3B-II/I and Parkin in hippocampal nerve cells were significantly increased (p < 0.05) in the NT group relative to the control. Meanwhile, mild hypothermia reduced the level of LC3B-II/I and Parkin (p < 0.05) relative to the NT group. Mild hypothermia protected mitochondria and improved neurological function following CA and resuscitation after ischemia/reperfusion (I/R) injury, likely by reducing excessive autophagy and mitophagy in neurons.
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Identification of a novel fusion gene (HLA-E and HLA-B) by RNA-seq analysis in esophageal squamous cell carcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-11-2014
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Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis.
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Celecoxib enhances radiosensitivity via induction of G?-M phase arrest and apoptosis in nasopharyngeal carcinoma.
Cell. Physiol. Biochem.
PUBLISHED: 03-23-2014
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Previous work has proposed that celecoxib may be able to enhance the effects of radiotherapy. However, the underlying mechanism of this activity has not yet been determined.
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HucMSC-exosome mediated -Wnt4 signaling is required for cutaneous wound healing.
Stem Cells
PUBLISHED: 03-10-2014
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Mesenchymal stem cell-derived exosomes (MSC-Ex) play important roles in tissue injury repair, however, the roles of MSC-Ex in skin damage repair and its mechanisms are largely unknown. Herein, we examined the benefit of human umbilical cord mesenchymal stem cell derived exosome (hucMSC-Ex) in cutaneous wound healing using a rat skin burn model. We found that hucMSC-Ex-treated wounds exhibited significantly accelerated re-epithelialization, with increased expression of CK19, PCNA, collagen I (compared to collagen III) in vivo. HucMSC-Ex promoted proliferation and inhibited apoptosis of skin cells after heat-stress in vitro. We also discovered that Wnt4 was contained in hucMSC-Ex, and hucMSC-Ex derived Wnt4 promoted ?-catenin nuclear translocation and activity to enhance proliferation and migration of skin cells, which could be reversed by ?-catenin inhibitor ICG001. In vivo studies confirmed that the activation of Wnt/?-catenin by hucMSC-Ex played a key role in wound re-epithelialization and cell proliferation. Furthermore, knockdown of Wnt4 in hucMSC-Ex abrogated ?-catenin activation and skin cell proliferation and migration in vitro. The in vivo therapeutic effects were also inhibited when the expression of Wnt4 in hucMSC-Ex was interfered. In addition, the activation of AKT pathway by hucMSC-Ex was associated with the reduction of heat stress-induced apoptosis in rat skin burn model. Collectively, our findings indicate that exosome-delivered Wnt4 provides new aspects for the therapeutic strategy of MSCs in cutaneous wound healing. Stem Cells 2014.
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Bioactive compound reveals a novel function for ribosomal protein S5 in hepatic stellate cell activation and hepatic fibrosis.
Hepatology
PUBLISHED: 03-10-2014
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Liver fibrosis and its endstage, cirrhosis, represent a major public health problem worldwide. Activation of hepatic stellate cells (HSCs) is a central event in hepatic fibrosis. However, the proteins that control HSC activation are incompletely understood. Here we show that (6aS, 10S, 11aR, 11bR, 11cS)-10-methylamino-dodecahydro-3a, 7a-diaza-benzo [de]anthracene-8-thione (MASM) exhibits potent inhibitory activity against liver fibrosis in vitro and in vivo associated with the reduction of Akt phosphorylation. Furthermore, ribosomal protein S5 (RPS5) was identified as a direct target of MASM, which stabilized RPS5 in cultured HSCs and in the liver of experimental animals after dimethylnitrosamine (DMN) or bile duct ligation (BDL). Functional studies revealed that RPS5 could prevent HSC activation. RPS5 overexpression in HSCs resulted in Akt dephosphorylation at both Ser473 and Thr308, and led to subsequent dephosphorylation of GSK3? or P70S6K. Progression of DMN- and BDL-induced hepatic fibrosis was aggravated by Rps5 knockdown and alleviated by RPS5 overexpression, which correlated with the modulation of Akt phosphorylation and HSC number in the fibrotic livers. Moreover, RPS5 was substantially reduced in the transdifferentiated HSCs, experimental fibrotic livers, and human cirrhosis samples.
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Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-09-2014
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This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression.
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Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats.
World J. Gastroenterol.
PUBLISHED: 03-04-2014
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To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved.
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Initial experience of correlating parameters of intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging at 3.0 T in nasopharyngeal carcinoma.
Eur Radiol
PUBLISHED: 02-05-2014
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To determine the correlation between intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters.
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Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-?B and signal transducer and activator of transcription 3 pathways.
Exp. Biol. Med. (Maywood)
PUBLISHED: 02-05-2014
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Increasing evidence has demonstrated that mesenchymal stem cells (MSCs)-mediated regulation of macrophages is critical for inflammation response and tissue injury repair. However, the underlying mechanism is not well understood. In this study, we investigated the effect of mouse bone marrow-derived MSCs on macrophages under normal and inflammatory conditions. Co-culture with MSCs or treatment with MSC-conditioned medium (MSC-CM) reduced the expression of tumor necrosis factor-? while inducing the expression of interleukin 10 (IL-10) and arginase 1 in lipopolysaccharide (LPS)-stimulated mouse RAW264.7 cells and splenic CD11b(+) cells. MSC-CM treatment increased the expression of CD206, a marker of alternatively activated M2 macrophages, in RAW264.7 cells. In addition, MSC-CM promoted the proliferation and migration of RAW264.7 cells. MSC-CM treatment activated signal transducer and activator of transcription 3 (STAT3) but inhibited nuclear factor-?B (NF-?B) pathways in LPS-stimulated RAW264.7 cells. Moreover, STAT3 inhibitor S3I-201 antagonized the induction of IL-10, arginase 1, and CD206 by MSC-CM in RAW264.7 cells. Conclusively, our findings suggest that mouse MSCs induce macrophage M2 activation through the NF-?B and STAT3 pathways.
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PTD-mediated intracellular delivery of mutant NFAT minimum DNA binding domain inhibited the proliferation of T cells.
Int. Immunopharmacol.
PUBLISHED: 01-03-2014
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The nuclear factor of activated T cell (NFAT) family of calcium-regulated transcription factors plays a key role in the development and function of the immune system. Calcineurin, a protein phosphatase, activates NFAT by dephosphorylation. The activated NFAT is translocated into the nucleus, where it up-regulates the expression of interleukin 2 (IL-2) and other target genes. Calcineurin inhibitors such as cyclosporine A (CsA) and FK506 are effective immunosuppressant drugs and dramatically increase the success rate of organ transplantation procedures. However, since calcineurin is expressed in most tissues in the body and calcineurin inhibition alters many cellular processes besides immune cell activation, the therapeutic use of calcineurin inhibitors is limited by serious side effects. Thus inhibiting NFAT by other mechanisms such as blocking its binding to DNA could be a more selective and safer approach to target NFAT for therapeutic applications. In peripheral T cells, productive immune responses are dependent upon the cooperative binding of the NFAT/AP-1 transcriptional complex to the promoter regions of genes such as interleukin-2 (IL-2), while NFAT in the absence of AP-1 leads to T cell anergy. Protein transduction domains (PTDs) are able to penetrate cell membranes and can be used to transport exogenous proteins across the cell and nuclear membranes. In this study, we constructed a fusion protein of PTD and a minimum DNA binding domain of human NFAT1 (PTD-?NFATminiDBD), which contains two mutations (R466A and T533G) in the AP-1 binding sites. The delivery and functions of this fusion protein in T cells were investigated. The results indicated that PTD-?NFATminiDBD could be effectively delivered into T cells and transported into the nucleus. PTD-?NFATminiDBD attenuated IL-2 production in T cells and then inhibited T cell proliferation, likely through competing against endogenous NFAT for binding to the IL-2 gene promoter. These results demonstrated that PTD-?NFATminiDBD was an effective NFAT inhibitor with a novel mechanism of action and might potentially be used as an immunosuppressant for organ transplantation with higher safety and better tolerance than calcineurin inhibitors.
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Activation of mesenchymal stem cells by macrophages prompts human gastric cancer growth through NF-?B pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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Accumulating evidence indicate that macrophages activate mesenchymal stem cells (MSCs) to acquire pro-inflammatory phenotype. However, the role of MSCs activated by macrophages in gastric cancer remains largely unknown. In this study, we found that MSCs were activated by macrophages to produce increased levels of inflammatory cytokines. Cell colony formation and transwell migration assays revealed that supernatants from the activated MSCs could promote both gastric epithelial cell and gastric cancer cell proliferation and migration. In addition, the expression of epithelial-mesenchymal transition (EMT), angiogenesis, and stemness-related genes was increased in activated MSCs. The phosphorylated forms of NF-?B, ERK and STAT3 in gastric cells were increased by active MSCs. Inhibition of NF-?B activation by PDTC blocked the effect of activated MSCs on gastric cancer cells. Co-injection of activated MSCs with gastric cancer cells could accelerate gastric cancer growth. Moreover, human peripheral blood monocytes derived macrophages also activated MSCs to prompt gastric cancer cell proliferation and migration. Taken together, our findings suggest that MSCs activated by macrophage acquire pro-inflammatory phenotype and prompt gastric cancer growth in an NF-?B-dependent manner, which provides new evidence for the modulation of MSCs by tumor microenvironment and further insight to the role of stromal cells in gastric carcinogenesis and cancer progression.
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Distinct pathways of ERK1/2 activation by hydroxy-carboxylic acid receptor-1.
PLoS ONE
PUBLISHED: 01-01-2014
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Mechanistic investigations have shown that, upon agonist activation, hydroxy-carboxylic acid receptor-1(HCA1) couples to a Gi protein and inhibits adenylate cyclase activity, leading to inhibition of liberation of free fatty acid. However, the underlying molecular mechanisms for HCA1 signaling remain largely unknown. Using CHO-K1 cells stably expressing HCA1, and L6 cells, which endogenously express rat HCA1 receptors, we found that activation of ERK1/2 by HCA1 was rapid, peaking at 5 min, and was significantly blocked by pertussis toxin. Furthermore, time course experiments with different kinase inhibitors demonstrated that HCA1 induced ERK1/2 activation via the extracellular Ca2+, PKC and IGF-I receptor transactivation-dependent pathways. In addition, we observed that pretreated the cells with M119K, an inhibitor of G?? subunit-dependent signaling, effectively attenuated the ERK1/2 activation triggered by HCA1, suggesting a critical role for ??-subunits in HCA1-activated ERK1/2 phosphorylation. Furthermore, the present results also indicated that the arrestin2/3 were not required for ERK1/2 activation. In conclusion, our findings demonstrate that upon binding to agonist, HCA1 receptors initially activate Gi, leading to dissociation of the G?? subunit from activated Gi, and subsequently induce ERK1/2 activation via two distinct pathways: one PKC-dependent pathway and the other IGF-IR transactivation-dependent pathway. Our results provide the first in-depth evidence that defines the molecular mechanism of HCA1-mediated ERK1/2 activation.
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Prognostic role of NLR in urinary cancers: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Recently, many studies explored the role of inflammation parameters such as neutrophil-to-lymphocyte ratio (NLR) in the prognosis of urinary cancers, but the results were not consistent.
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The assessment of pulsed dye laser treatment of port-wine stains with reflectance confocal microscopy.
J Cosmet Laser Ther
PUBLISHED: 12-14-2013
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Background: Reflectance confocal microscopy (RCM) is a noninvasive technique for evaluating cutaneous lesions with cellular level resolution close to conventional histopathology. The aim of this study is to observe the vascular changes in Port-wine (PWS) lesions and assess the clinical efficacy of Pulsed Dye Laser (PDL) treatment by examining vessel diameter and density with RCM. Materials and methods: Eleven adult patients with PWS, each had four test patches carried out with different pulse durations (1.5, 3, 6, and 10 ms), respectively; fluences of 9-12 J/cm(2); and a spot size of 7 mm. The PDL treatment was repeated 3-5 times at a 2-month interval. Photographs and measurements with RCM were taken before each treatment and 2 months after the last treatment. Results: The PDL treatment exhibited increasing clearance with reducing pulse durations. Vessel diameters and densities were significantly decreased in the same pulse-duration groups after treatment. There was significant difference between 1.5 ms pulse-duration group and other pulse-duration groups in reducing blood vessel diameter at the depth of 150 ?m. Conclusions: RCM can be used to assess the clinical efficacy of PDL treatment.
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[Comparison of the targeting properties of 2-deoxy-D-glucose-conjugated nanoparticles to breast cancer MDA-MB-231 cells and breast fibroblasts cells and breast fibroblasts].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 12-10-2013
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To compare the differences in uptake of 2-deoxy-D-glucose (2-DG)-conjugated nanoparticles between breast carcinoma MDA-MB-231 cells with high metabolism and breast fibroblasts with normal metabolism, and investigate the feasibility of using the coated nanoparticles as a MRI-targeted contrast agent for highly metabolic carcinoma cells.
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Organocatalytic enantioselective synthesis of 2,3-allenoates by intermolecular addition of nitroalkanes to activated enynes.
J. Am. Chem. Soc.
PUBLISHED: 11-21-2013
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The first efficient intermolecular addition of nitroalkanes to activated enynes for asymmetric synthesis of 2,3-allenoates is described. It is a new addition to the limited available strategies for catalytic asymmetric synthesis of allenoates. Enabled by a new bifunctional catalyst, a range of trisubstituted allenoates can be obtained in excellent chemical and optical purity. These allenoate products with a pendant 2-nitroethyl ?-substituent are useful chiral building blocks.
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Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and chronic renal injury.
Exp. Biol. Med. (Maywood)
PUBLISHED: 08-24-2013
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Mesenchymal stem cell is becoming a promising candidate in acute kidney injury (AKI). We first reported that human umbilical cord mesenchymal stem cells (hucMSCs) could ameliorate renal function in ischemic/reperfusion AKI rats, but the role of hucMSCs in cisplatin-induced acute and chronic injury has been demonstrated. More specifically, it is still unknown whether hucMSCs halt renal interstitial fibrosis. In this study, we investigated the effect of hucMSCs in cisplatin-induced kidney injury and explored the mechanism of action. Blood urea nitrogen (BUN) and creatinine (Cr) analyses showed amelioration of functional parameters in hucMSC-treated rats at early damage. Transplantation with hucMSCs promoted renal cell regeneration, inhibited cell apoptosis, abrogated inflammatory responses and protected mitochondria. Moreover, Massons trichrome staining demonstrated reduced levels of fibrosis in kidney tissues of hucMSC-treated rats at six and eight weeks after cisplatin injection. These results were corroborated by reduced collagen deposit, the ratio of Bax to Bcl-2 and transforming growth factor ? mRNA expression. Furthermore, hucMSCs prevented the epithelial-mesenchymal transition (EMT) in injury renal tissues, leading to the attenuation of chronic renal interstitial fibrosis. Taken together, our findings suggested that hucMSCs could decrease the kidney from development of later renal interstitial fibrosis by amelioration of early AKI.
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Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and chronic renal injury.
Exp. Biol. Med. (Maywood)
PUBLISHED: 08-20-2013
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Mesenchymal stem cell is becoming a promising candidate in acute kidney injury (AKI). We first reported that human umbilical cord mesenchymal stem cells (hucMSCs) could ameliorate renal function in ischemic/reperfusion AKI rats, but the role of hucMSCs in cisplatin-induced acute and chronic injury has been demonstrated. More specifically, it is still unknown whether hucMSCs halt renal interstitial fibrosis. In this study, we investigated the effect of hucMSCs in cisplatin-induced kidney injury and explored the mechanism of action. Blood urea nitrogen (BUN) and creatinine (Cr) analyses showed amelioration of functional parameters in hucMSC-treated rats at early damage. Transplantation with hucMSCs promoted renal cell regeneration, inhibited cell apoptosis, abrogated inflammatory responses and protected mitochondria. Moreover, Massons trichrome staining demonstrated reduced levels of fibrosis in kidney tissues of hucMSC-treated rats at six and eight weeks after cisplatin injection. These results were corroborated by reduced collagen deposit, the ratio of Bax to Bcl-2 and transforming growth factor ? mRNA expression. Furthermore, hucMSCs prevented the epithelial-mesenchymal transition (EMT) in injury renal tissues, leading to the attenuation of chronic renal interstitial fibrosis. Taken together, our findings suggested that hucMSCs could decrease the kidney from development of later renal interstitial fibrosis by amelioration of early AKI.
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[Multiple factors related with intracranial hemorrhage of dural arteriovenous fistula: clinical analysis].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-02-2013
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To discuss the relevant predicative factors of dural arteriovenous fistula (dAVF) in intracranial hemorrhage.
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Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor.
Eur J Med Chem
PUBLISHED: 08-01-2013
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Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer and other diseases, and lots of efforts have been put into the development of organic compounds as more potent PARP-1 inhibitors. Here we describe a strategy to conveniently obtain metal-based PARP-1 inhibitors with enhanced biological activities by conjugating platinum moiety with an original inhibitor, e.g., benzonaphthyridone. Based on the structure-activity relationship analysis of PARP-1 inhibitors, three platinated PARP-1 inhibitors were designed, and the complexes were synthesized and characterized. Complex 3 presented significantly enhanced cytotoxicity against a panel of human cancer cells and a 10-fold increased inhibitory effect against recombinant PARP-1 compared with the original PARP-1 inhibitor. Complex 3 was as cytotoxic as cisplatin and its spectrum of anticancer activity was identical to that of cisplatin. The complex was able to enter into cancer cells efficiently, bind to DNA well, and block cell cycle at G2/M phase, indicating that complex 3 is an effective anticancer agent with a distinct mechanism of action. Our study implies that the conjugation of platinum with PARP-1 inhibitors could be a valid strategy to obtain more potent anticancer agents with improved biological activities.
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Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice.
J Transl Med
PUBLISHED: 07-25-2013
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Angiotensin-converting enzyme 2 (ACE2), a monocarboxypeptidase which metabolizes angiotensin II (Ang II) to generate Ang-(1-7), has been shown to prevent cardiac hypertrophy and injury but the mechanism remains elusive. Irbesartan has the dual actions of angiotensin receptor blockade and peroxisome proliferator-activated receptor-? (PPAR?) activation. We hypothesized that irbesartan would exert its protective effects on ACE2 deficiency-mediated myocardial fibrosis and cardiac injury via the PPAR? signaling.
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H. pylori infection-induced MSC differentiation into CAFs promotes epithelial-mesenchymal transition in gastric epithelial cells.
Int. J. Mol. Med.
PUBLISHED: 07-24-2013
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Mesenchymal stem cell (MSC) tropism to injured tissue sites in response to inflammation and wounds has been suggested. MSC activation and recruitment by Helicobacter pylori (H. pylori)-infected gastrointestinal epithelial cells has been demonstrated. As a component of the chronic gastritis microenvironment, MSCs play critical roles in the development of H. pylori-associated gastric mucosal lesions/malignancies. However, the mechanisms responsible for this process remain largely unknown. In this study, we demonstrate that H. pylori infection induces the differentiation of MSCs into cancer-associated fibroblast (CAF)-like cells. H. pylori-infected MSCs possessed an altered cytokine profile and induced epithelial-mesenchymal transition in gastric epithelial cells, leading to destroyed cell junctions, enhanced cell migration, reduced cell apoptosis and increased oncogenic potential. In conclusion, our findings indicate that H. pylori infection may cause gastric lesions/malignancies by inducing the differentiation of MSCs into CAFs and suggest a novel mechanism of action and role of MSCs in the development and progression of gastric cancer.
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Smoking spaces as enabling spaces of wellbeing.
Health Place
PUBLISHED: 07-09-2013
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A persistent emphasis on the negative biomedical effects of cigarette smoking effectively glosses over the affectual-sensual and social wellbeing that smoking can enable. In addition, while tobacco research has recently been more attuned to the stigmatizing affects brought about by smoking de-normalization efforts, a lot less attention has been placed on how smokers negotiate these feelings of stigmatization so as to restore their personal spaces of wellbeing. In this paper, I situate my investigation of smoking geographies in the burgeoning literature on enabling spaces which focuses on how places co-constitute our ability to act/affect in empowering ways. By deploying qualitative research methods such as in-depth interviews, I argue that an acknowledgment of how smoking spaces in Singapore can be enabling along affectual, sensorial and social registers is long overdue. While it is not my purpose to systematically downplay the damaging health effects that smoking can engender, a focus on enabling smoking spaces emphasizes the role of smokers as creative agents capable of (re)fashioning their own holistic and subjective versions of wellbeing. In so doing, I hope to contribute to the existing research on smoking spaces and a recent profusion of work on relational geographies of affect.
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Experimental therapy for lung cancer: umbilical cord-derived mesenchymal stem cell-mediated interleukin-24 delivery.
Curr Cancer Drug Targets
PUBLISHED: 06-26-2013
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The use of adult stem cells as gene delivery vehicles is a novel and attractive strategy for cancer therapy. Mesenchymal stem cells (MSCs) provide a promising source for stem cell-based gene therapies. Interleukin-24 (IL24) has been suggested as an effective anticancer agent. However, a lack of tumor-targeted delivery and a host immune response to viral vehicles has hindered its application for cancer therapy. In this study, we evaluated the effects of IL24 delivered by MSCs as a therapeutic approach for lung cancer. We engineered human umbilical cord-derived MSCs (UC-MSCs) to efficiently deliver secretable IL24. We observed that IL24-transduced UC-MSCs (IL24-MSCs) inhibited the growth of A549 lung cancer cells by induction of apoptosis and cell cycle arrest. The IL24 proteins secreted by IL24-MSCs were involved in regulating the ERK-1/2, AKT and JNK signaling pathways. Additionally, MSCs-mediated IL24 expression led to an increase in the cleavage of caspases-3/8/9 and PARP, the Bax/Bcl-2 ratio, as well as the p21 expression in A549 cells. We also demonstrated that injection of IL24-MSCs significantly suppressed xenograft tumor growth. Moreover, the IL24-MSCs had anti-angiogenic effects both in vitro and in vivo. Taken together, our findings indicate that IL24 delivered by human UC-MSCs has the potential to be used as an alternative strategy for lung cancer therapy.
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Dynamic assessment of lung injury by ultrasound in a case with H7N9 influenza.
Crit Care
PUBLISHED: 06-18-2013
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H7N9 influenza is a new emerging infection and has high mortality. Both chest radiography and computed tomography (CT) had some limitations in assessing such patients. We performed daily lung ultrasound in a patient with H7N9 influenza. Lung ultrasound and lung ultrasound score showed high consistency with CT and the progression of pneumonia. Ultrasound can be adjutant to chest radiography and CT in caring for patients with H7N9 influenza.
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Multifunctional structural supercapacitor composites based on carbon aerogel modified high performance carbon fiber fabric.
ACS Appl Mater Interfaces
PUBLISHED: 06-07-2013
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A novel multifunctional material has been designed to provide excellent mechanical properties while possessing a high electrochemical surface area suitable for electrochemical energy storage: structural carbon fiber fabrics are embedded in a continuous network of carbon aerogel (CAG) to form a coherent but porous monolith. The CAG-modification process was found to be scalable and to be compatible with a range of carbon fiber fabrics with different surface properties. The incorporation of CAG significantly increased the surface area of carbon fiber fabrics, and hence the electrochemical performance, by around 100-fold, resulting in a CAG-normalized specific electrode capacitance of around 62 F g(-1), determined by cyclic voltammetry in an aqueous electrolyte. Using an ionic liquid (IL) electrolyte, the estimated energy density increased from 0.003 to 1 Wh kg(-1), after introducing the CAG into the carbon fiber fabric. Proof-of-concept multifunctional structural supercapacitor devices were fabricated using an IL-modified solid-state polymer electrolyte as a multifunctional matrix to provide both ionic transport and physical support for the primary fibers. Two CAG-impregnated carbon fabrics were sandwiched around an insulating separator to form a functioning structural electrochemical double layer capacitor composite. The CAG-modification not only improved the electrochemical surface area, but also reinforced the polymer matrix surrounding the primary fibers, leading to dramatic improvements in the matrix-dominated composite properties. Increases in in-plane shear strength and modulus, of up to 4.5-fold, were observed, demonstrating that CAG-modified structural carbon fiber fabrics have promise in both pure structural and multifunctional energy storage applications.
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Multi-targeted organometallic ruthenium(II)-arene anticancer complexes bearing inhibitors of poly(ADP-ribose) polymerase-1: A strategy to improve cytotoxicity.
J. Inorg. Biochem.
PUBLISHED: 05-17-2013
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Small-molecule inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have currently drawn much attention as promising chemotherapeutic drug candidates, and there is a need to develop more potent PARP inhibitors with improved bioavailability. Here we report a strategy to improve the cytotoxicity of PARP inhibitors by conjugation with organometallic ruthenium(II)-arene compounds. We also report a systematic study to reveal the mechanism of action of these ruthenium-PARP inhibitor conjugates. The complexes have been synthesized and characterized spectroscopically. The improved antiproliferative activity from the as-prepared complexes in four human cancer cell lines has indicated their potential for further development as antitumor drugs. Cellular uptake study reveals that the most active complex 3 easily entered into cells. Target validation assays show that the complexes inhibited PARP-1 slightly better than the original PARP inhibitors, that complex 3 strongly bound to DNA and inhibited transcription, and that this complex arrested the cell cycle at the G0/G1 stage. This type of information could shed light on the design of the next generation of more active ruthenium-PARP inhibitor conjugates.
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Origin and assessment of groundwater pollution and associated health risk: a case study in an industrial park, northwest China.
Environ Geochem Health
PUBLISHED: 04-15-2013
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Groundwater quality which relates closely to human health has become as important as its quantity due to the demand for safe water. In the present study, an entropy-weighted fuzzy water quality index (WQI) has been proposed for performing groundwater quality assessment in and around an industrial park, northwest China, where domestic water requirements are solely met by groundwater. The human health risk was assessed with the model recommended by the United States Environmental Protection Agency. In addition, the sources of major ions and main contaminants were also analyzed. The study shows that groundwater in the study area has been contaminated conjunctively by natural processes and industrial and agricultural activities. Nitrate, manganese (Mn), fluoride, total dissolved solids, total hardness and sulfate are major contaminants influencing groundwater quality. Nitrate and heavy metals such as Mn are mainly affected by human agricultural activities and industrial production, while other contaminants are mainly originated from mineral weathering and water-rock interactions. The results of water quality assessment suggest that half of the groundwater samples collected are of medium quality thus require pretreatment before human consumption. The mean health risk caused by the consumption of contaminated groundwater in the area is 8.42 × 10(-5) per year which surpasses the maximum acceptable level (5 × 10(-5) per year) recommended by the International Commission on Radiologic Protection. The entropy-weighted fuzzy WQI proposed in this study can not only assign proper weights to parameters but also treat uncertainties associated with water quality classification. This study will be of interest to international environmentalists and hydrogeologists. It will also be useful in regional groundwater management and protection.
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Enhancement effect of dihydroartemisinin on human ?? T cell proliferation and killing pancreatic cancer cells.
Int. Immunopharmacol.
PUBLISHED: 04-04-2013
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?? T cells play important roles in innate immunity against tumors and infections. Inhibitory effect of dihydroartemisinin on growth of cancer cells has been found in recent years. In this study, we investigated the effect of dihydroartemisinin on human ?? T cell proliferation by MTT assay and killing activity against pancreatic cancer cells SW1990, BxPC-3 and PANC-1 by LDH release assay in vitro. Intracellular molecule alterations were verified by flow cytometry. The results suggested that appropriate concentration of dihydroartemisinin favored the expansion of ?? T cells and enhanced ?? T cell mediated killing activity against pancreatic cancer cells. Up-regulation of intracellular perforin, granzyme B expression and IFN-? production may be the important mechanism of dihydroartemisinin on increased antitumor activity of ?? T cells.
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Two pairs of 1 : 2 nickel(II) and copper(II) metal-complex dyes showing the same trans configuration and azo-hydrazone transformation but different thermal properties.
Dalton Trans
PUBLISHED: 03-30-2013
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Two pairs of 1: 2 neutral trans mononuclear transition-metal (M = Ni(II) and Cu(II)) complexes of pyridine-2,4-dione and quinoline-2,4-dione based heterocyclic dyes have been structurally and spectrally characterized and compared herein. X-ray single-crystal diffraction analyses of four complexes, namely trans-[Ni(La)2(DMF)2] (1), trans-[Cu(La)2(DMF)2] (2), trans-[Ni(Lb)2(DMF)2] (3) and trans-[Cu(Lb)2(DMF)2] (4), reveal that they have the same trans configuration between the bidentate chelating dianionic ligands and two axially coordinated DMF molecules. Furthermore, a transformation from the hydrazone to azo configuration has been observed for both bidentate chelating ligands La(-) and Lb(-) after metal-ion complexation. More importantly, the simultaneous DSC/TG-MS-FTIR method has been used to explore the thermal stability of four neutral metal-complex dyes 1-4, where the two axially coordinated DMF molecules in Ni(II) and Cu(II) complexes exhibit distinguishable decomposition behavior because of their different M-O bond lengths originating from the Jahn-Teller distortions.
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Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 03-26-2013
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Serotonin (5-HT) neurons synthesize a variety of peptides. How these peptides are controlled during development remains unclear. It has been reported that the co-localization of peptides and 5-HT varies by species. In contrast to the situations in the rostral 5-HT neurons of human and rat brains, several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain. In this study, we found that the peptide substance P and peptide genes, including those encoding peptides thyrotropin-releasing hormone, enkephalin, and calcitonin gene-related peptide, were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons. We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate. Furthermore, we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate. By examining the phenotype of Lmx1b deletion mice, we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons. Together, our results indicate that Lmx1b, a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis, determines some peptide phenotypes in these neurons as well.
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Myocardial infarction in singapore: ethnic variation in evidence-based therapy and its association with socioeconomic status, social network size and perceived stress level.
Heart Lung Circ
PUBLISHED: 03-15-2013
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Singapore is a multiethnic Asian country comprising predominantly Chinese, Malays, and Indians. We sought to study the disparities in evidence-based therapy for people from these three ethnic groups who were admitted to hospital with ST-segment elevation myocardial infarction (STEMI). We also examined its association with socioeconomic level and social network size and the influence on psychological stress level.
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Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro.
Stem Cell Res Ther
PUBLISHED: 03-08-2013
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INTRODUCTION: Administration of bone marrow mesenchymal stem cells (MSCs) or secreted microvesicles improves recovery from acute kidney injury (AKI). However, the potential roles and mechanisms are not well understood. In the current study, we focused on the protective effect of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) on cisplatin-induced nephrotoxicity in vivo and in vitro. METHODS: We constructed cisplatin-induced AKI rat models. At 24 h after treatment with cisplatin, hucMSC-ex were injected into the kidneys via the renal capsule; human lung fibroblast (HFL-1)-secreted exosomes (HFL-1-ex) were used as controls. All animals were killed at day 5 after administration of cisplatin. Renal function, histological changes, tubular apoptosis and proliferation, and degree of oxidative stress were evaluated. In vitro, rat renal tubular epithelial (NRK-52E) cells were treated with or without cisplatin and after 6 h treated with or without exosomes. Cells continued to be cultured for 24 h, and were then harvested for western blotting, apoptosis and detection of degree of oxidative stress. RESULTS: After administration of cisplatin, there was an increase in blood urea nitrogen (BUN) and creatinine (Cr) levels, apoptosis, necrosis of proximal kidney tubules and formation of abundant tubular protein casts and oxidative stress in rats. Cisplatin-induced AKI rats treated with hucMSC-ex, however, showed a significant reduction in all the above indexes. In vitro, treatment with cisplatin alone in NRK-52E cells resulted in an increase in the number of apoptotic cells, oxidative stress and activation of the p38 mitogen-activated protein kinase (p38MAPK) pathway followed by a rise in the expression of caspase 3, and a decrease in cell multiplication, while those results were reversed in the hucMSCs-ex-treated group. Furthermore, it was observed that hucMSC-ex promoted cell proliferation by activation of the extracellular-signal-regulated kinase (ERK)1/2 pathway. CONCLUSIONS: The results in the present study indicate that hucMSC-ex can repair cisplatin-induced AKI in rats and NRK-52E cell injury by ameliorating oxidative stress and cell apoptosis, promoting cell proliferation in vivo and in vitro. This suggests that hucMSC-ex could be exploited as a potential therapeutic tool in cisplatin-induced nephrotoxicity.
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Perturbation of MicroRNA-370/Lin-28 homolog A/nuclear factor kappa B regulatory circuit contributes to the development of hepatocellular carcinoma.
Hepatology
PUBLISHED: 02-20-2013
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MicroRNA 370 (miR-370) is located within the DLK1/DIO3 imprinting region on human chromosome 14, which has been identified as a cancer-associated genomic region. However, the role of miR-370 in malignances remains controversial. Here, we report that miR-370 was repressed in human hepatocellular carcinoma (HCC) tissues and hepatoma cell lines. Using gain-of-function and loss-of-function experiments, we demonstrated that miR-370 inhibited the malignant phenotype of HCC cells in vitro. Overexpression of miR-370 inhibited growth and metastasis of HCC cells in vivo. Moreover, the RNA-binding protein, LIN28A, was identified as a direct functional target of miR-370, which, in turn, blocked the biogenesis of miR-370 by binding to its precursor. LIN28A also mediated the suppressive effects of miR-370 on migration and invasion of HCC cells by post-transcriptionally regulating RelA/p65, which is an important effector of the canonical nuclear factor kappa B (NF-?B) pathway. Interleukin-6 (IL-6), a well-known NF-?B downstream inflammatory molecule, reduced miR-370 but increased LIN28A levels in HCC. Furthermore, miR-370 levels were inversely correlated with LIN28A and IL-6 messenger RNA (mRNA) levels, whereas LIN28A mRNA expression was positively correlated with IL-6 expression in human HCC samples. Interestingly, reduction of miR-370 expression was associated with the development of HCC in rats, as well as with aggressive tumor behavior and short survival in HCC patients. Conclusions: These data demonstrate the involvement of a novel regulatory circuit consisting of miR-370, LIN28A, RelA/p65 and IL-6 in HCC progression. Manipulating this feedback loop may have beneficial effect in HCC treatment. (Hepatology 2013; 58:1977-1991).
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Hydrogen-rich medium suppresses the generation of reactive oxygen species, elevates the Bcl-2/Bax ratio and inhibits advanced glycation end product-induced apoptosis.
Int. J. Mol. Med.
PUBLISHED: 02-20-2013
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The purpose of the present study was to determine whether using hydrogen-rich medium (HRM) to increase hydrogen levels in endothelial cells (ECs) protects ECs from apoptosis induced by advanced glycation end products (AGEs). The thoracic aorta was removed from 2-3-year-old Sprague-Dawley rats, and ECs were isolated and cultured. After culturing ECs in the presence of AGEs and/or with HRM for 24 h, Annexin V/7-AAD and TUNEL staining were carried out to detect apoptosis. Intracellular ROS were detected by fluorescent probe and quantified by flow cytometry. The expression of antioxidative enzymes (superoxide dismutase, glutathione peroxidase) was determined by real-time PCR analysis and enzymatic assay. The relative expression levels of Bcl-2 and Bax were analyzed by western blotting. The addition of AGEs increased the apoptosis of ECs in a concentration-dependent manner and HRM reduced the AGE (400 µg/ml)-induced apoptosis from 21.61±2.52 to 11.32±1.75%. HRM also significantly attenuated the AGE-induced intracellular ROS induction and decrease in the expression of antioxidative enzymes. In conclusion, hydrogen exhibits significant protective effects against AGE-induced EC injury possibly through reducing ROS generation, intracellular antioxidant enzyme system protection and elevation of the Bcl-2/Bax ratio.
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Two new compounds from Scolopendra multidens Newport.
J Asian Nat Prod Res
PUBLISHED: 02-18-2013
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Two new compounds, 5?-pregnane-2?,6?,20(S)-triol (1) and 8-hydroxyl-3-methoxyl-2(1H)-quinolone (2), were isolated from Scolopendra multidens Newport. Their structures were elucidated on the basis of spectroscopic methods including 1D and 2D NMR and HR-TOF-MS.
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Macrophages are involved in the protective role of human umbilical cord-derived stromal cells in renal ischemia-reperfusion injury.
Stem Cell Res
PUBLISHED: 01-16-2013
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Administration of fibroblastic cells derived from a number of tissues (collectively called "mesenchymal stem cells") has been suggested to be beneficial for renal repair and mortality reduction in renal ischemia-reperfusion injury (IRI), but the underlying mechanism is not fully understood. In the present study, our objective was to investigate the involvement of macrophages in the therapeutic effect of human umbilical cord-derived stromal cells (hUCSCs) on renal IRI. Twenty-four hours after reperfusion, hUCSCs were injected intravenously and resulted in significant improvements in renal function, with a lower tubular injury score together with more proliferative and fewer apoptotic tubular cells in kidney tissue. Moreover, hUCSCs reduced the infiltration of macrophages into renal interstitium especially at 5 days post-reperfusion, while the proportion of anti-inflammatory M2 macrophages was markedly increased. HUCSCs also alleviated the local inflammatory response in kidneys. The absence of macrophages during the early phase of reperfusion enhanced the therapeutic effect of hUCSCs, whereas macrophage depletion during the late repair phase eliminated the renoprotective role of hUCSCs. In vitro, macrophages cocultured with hUCSCs were switched to the alternatively activated M2 phenotype. Our data indicate that hUCSCs are capable of promoting the M2 polarization of macrophages at injury sites, suggesting a new mechanism for hUCSC-mediated protection in renal IRI.
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miR-17-5p/20a are important markers for gastric cancer and murine double minute 2 participates in their functional regulation.
Eur. J. Cancer
PUBLISHED: 01-16-2013
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To investigate the potential roles and mechanisms of miR-17-5p/20a in human gastric cancer development and progression.
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Mesenchymal stem cell-like cells from children foreskin inhibit the growth of SGC-7901 gastric cancer cells.
Exp. Mol. Pathol.
PUBLISHED: 01-07-2013
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Mesenchymal stem cells (MSCs) become a research hotspot in recent years because of their roles in regenerative medicine and tissue injury repair. However, the limited source for MSCs hampers its clinical application. In this study, we isolated and identified human mesenchymal stem cell-like cells from foreskin (hFMSCs) by explant culture. HFMSCs had similar morphology and immunophenotype to that of human bone marrow derived-mesenchymal stem cells. HFMSCs formed colonies after 9 days of inoculation and could be propagated for more than 50 passages. HFMSCs had a normal karyotype and high G0/G1 phase independent of passage number. Further, hFMSCs could be induced to differentiate into osteocytes and adipocytes. We found that the growth of SGC-7901 (human gastric adenocarcinoma) cells could be suppressed by simultaneous injection of hFMSCs in vivo. HFMSCs also inhibited SGC-7901 cell proliferation in vitro. HFMSC co-injection resulted in a decrease in PCNA-positive and an increase in apoptotic tumor cells. HFMSCs derived conditioned medium inhibited the expression of BCL-2 while increased the expression of BAX and caspase-3 in SGC-7901 cells. Taken together, our findings suggest that children foreskin is a new source for MSCs and hFMSCs could inhibit gastric cancer cell growth both in vitro and in vivo.
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Severe obstructive sleep apnea and outcomes following myocardial infarction.
J Clin Sleep Med
PUBLISHED: 12-16-2011
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We sought to determine the effect of severe obstructive sleep apnea (OSA) on long-term outcomes after myocardial infarction. We hypothesized that severe OSA was associated with lower event-free survival rate after ST-segment elevation myocardial infarction (STEMI).
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Characteristics of patients with fluid extravasation during retrograde ureteroscopic holmium laser lithotripsy for renal calculi.
Saudi Med J
PUBLISHED: 12-14-2011
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To explore the risk factors of fluid extravasation during retrograde ureteroscopic holmium laser lithotripsy for renal calculi.
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[Impact of stromal interaction molecule 1 silencing on cell cycle of endothelial progenitor cells].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-18-2011
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To investigate the effect of stromal interaction molecule 1 (STIM1) silencing on EPCs cell cycle.
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[Wnt signaling pathway and the Evo-Devo of deuterostome axis].
Yi Chuan
PUBLISHED: 11-05-2011
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A series of signal transduction pathways have been found to regulate the polarity establishment and formation of animal primary body axis. Among them, Wnt signaling pathway is extremely conserved and several key components in the pathway have been identified in the demosponge lineage. This implies that it is one of the earliest pathways involved in the ancestral metazoan axis development and might play an important role in specification and development of posterior and ventral fate of animal axis. Recently, with the establishment of functional experiments in vitro, the body plan formation has been found to be affected, in varying degrees, by many genes in the Wnt signaling pathway, such as members of wnt gene family, maternal gene beta-catenin and some transcription factor encoding genes. In this review, we analyzed the evolutionary origin of the wnt gene family involved in development of metazoan body plans, and then made a brief review on the roles of canonical Wnt/beta-catenin signaling in the polarity establishment and formation of primary body axis in diverse deuterostomes including sea urchin, amphioxus, zebrafish, frog, and mouse.
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[Laser ablation and fast pulse discharge plasma spectroscopy analysis of Sn in soil].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 10-20-2011
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A developing technique, laser ablation and fast pulse discharge plasma spectroscopy technique (LA-FPDPS), was used for the first time to analyze the Sn concentration in soil. The peak intensity of Sn (284.0 nm) line from soil plasma emission was greatly enhanced in comparison with using the traditional single pulse (SP) LIBS system. Using the technique, calibration curve of Sn in soil was derived. The limit of detection (LOD) for Sn in soil was reduced to be 0.16 microg x g(-1). The value is significantly improved compared with the results reported in literature when using LIBS technique, which usually was between 8.2 to 54 microg x g(-1) depending on the experimental condition, indicating that this technique possibly will be useful for rapid quantitative elemental analysis in soil.
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Mapping local microstructure and mechanical performance around carbon nanotube grafted silica fibres: methodologies for hierarchical composites.
Nanoscale
PUBLISHED: 10-06-2011
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The introduction of carbon nanotubes (CNTs) modifies bulk polymer properties, depending on intrinsic quality, dispersion, alignment, interfacial chemistry and mechanical properties of the nanofiller. These effects can be exploited to enhance the matrices of conventional microscale fibre-reinforced polymer composites, by using primary reinforcing fibres grafted with CNTs. This paper presents a methodology that combines atomic force microscopy, polarised Raman spectroscopy, and nanoindentation techniques, to study the distribution, alignment and orientation of CNTs in the vicinity of epoxy-embedded micrometre-scale silica fibres, as well as, the resulting local mechanical properties of the matrix. Raman maps of key features in the CNT spectra clearly show the CNT distribution and orientation, including a parted morphology associated with long grafted CNTs. The hardness and indentation modulus of the epoxy matrix were improved locally by 28% and 24%, respectively, due to the reinforcing effects of CNTs. Moreover, a slower stress relaxation was observed in the epoxy region containing CNTs, which may be due to restricted molecular mobility of the matrix. The proposed methodology is likely to be relevant to further studies of nanocomposites and hierarchical composites.
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Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth.
Cell Cycle
PUBLISHED: 09-15-2011
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In previous studies, we and others have shown that bone marrow mesenchymal stem cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in mouse xenograft models, suggesting that interactions between MSCs and tumor cells may play an important role in this process. However, the exact mechanism remains unclear. In the present study, we investigated whether the physical presence or the continuous presence of MSCs is required for enhanced tumor growth, and we found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC-conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth comparable to the effect of MSC co-injection in vivo in mouse xenograft models. We further showed that significant tumor modifying activity is present in post-ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM induces the expression of VEGF of tumor cells as well as the activation of RhoA-GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in serial transplantation, suggesting that MSC-secreted factors have profound effects on "reprogramming" of tumor growth. Our data provide new insights into the way in which MSCs modify tumor growth and offer a new and exciting opportunity to develop effective therapeutics for intercepting tumor progression.
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[Effects of puerarin on proliferation and differentiation of umbilical cord mesenchymal stem cells into osteoblasts in vitro].
Yao Xue Xue Bao
PUBLISHED: 09-03-2011
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This study is to investigate the effects of puerarin on the proliferation and differentiation of umbilical cord mesenchymal stem cells (MSCs) into osteoblasts. Umbilical cord MSCs were cultured by tissue adherence and the third passage of cells was used in the experiment. The effect of puerarin on proliferation of umbilical cord MSCs was measured with MTT. The effects of puerarin on umbilical cord MSCs were evaluated by ALP immunohistochemisty and von kossa staining. The OD value decreased with the increase of puerarin concentration. On 7th day, ALP expression of puerarin group was higher than that of control group. On 14th day, ALP staining showed that the positive rate of puerarin group was higher than that of control group. Von kossa staining showed the quantity of calcium nodules was higher in puerarin group than that of control group. Puerarin can promote the umbilical cord MSCs to differentiate into osteoblasts and has an effect on the proliferation of umbilical cord MSCs.
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Groundwater quality assessment based on rough sets attribute reduction and TOPSIS method in a semi-arid area, China.
Environ Monit Assess
PUBLISHED: 08-24-2011
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In order to enrich and improve the groundwater quality assessment system, a new coupled assessment model based on rough set attribute reduction and the technique for order preference by similarity to ideal solution (TOPSIS) was proposed. The proposed model was applied in the groundwater quality assessment of a semi-arid area, northwest China. The results show that most chemical indices except NH (4) (+) , F(-), and Mn meet the Standards for Drinking Water of China and the groundwater quality overall is good. All assessed water samples are found to be fit for human consumption according to the comprehensive assessment results. Rough set attribute reduction for groundwater quality assessment is practical. The assessment results after attribute reduction show a good consistency with those before attribute reduction. Rough set attribute reduction and TOPSIS evaluation coupled model is clear in ideas and simple in calculation, and evaluation results are reasonable as well. The coupled model can be applied to solve many multiple criteria decision making problems such as groundwater quality assessment.
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[Studies on the chemical constituents in fruits of Acanthopanax gracilistylus].
Zhong Yao Cai
PUBLISHED: 08-10-2011
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To study the chemical constituents in the fruits of Acanthopanax gracilistylus.
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Treatment of café au lait macules in Chinese patients with a Q-switched 755-nm alexandrite laser.
J Dermatolog Treat
PUBLISHED: 07-31-2011
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Café au lait macules (CALMs) are a benign epidermal hyperpigmentation disorder. Although CALMs have been removed successfully with lasers, there have been few investigations on the use of the Q-switched 755-nm alexandrite laser.
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Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo.
Cancer Lett.
PUBLISHED: 07-28-2011
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Mesenchymal stem cells (MSCs) can promote tumor growth in a mouse xenograft model, but the exact mechanism remains unclear. In this study, we investigated the effects of bone marrow MSC-derived exosomes (MSC-exosomes) on tumor growth in vitro and in vivo. Our results showed that MSC-exosomes promoted tumor growth in vivo. MSC-exosomes enhanced vascular endothelial growth factor (VEGF) expression in tumor cells by activating extracellular signal-regulated kinase1/2 (ERK1/2) pathway. Inhibition of ERK1/2 activation reserved the increase of VEGF level by MSC-exosomes. Our findings demonstrate a new mechanism through which MSC-exosome-mediated cell-cell interactions may contribute to tumor progression.
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4,4-(Cyclo-hexane-1,1-di-yl)dianilinium dichloride monohydrate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 07-15-2011
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In the title compound, C(18)H(24)N(2) (2+)·2Cl(-)·H(2)O, both the cation and the water mol-ecule lie on a twofold crystallographic axis. In the cation, the two benzene rings are perpendicular to each other, making a symmetry-constrained dihedral angle of 90°. In the crystal, N-H?Cl, O-H?Cl and N-H?O hydrogen bonds result in the formation of a three-dimensional network.
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3,3-Dichloro-biphenyl-4,4-diaminium sulfate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 07-11-2011
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In the title compound, C(12)H(12)Cl(2)N(2) (2+)·SO(4) (2-), the two rings are not coplanar [dihedral angle = 48.7?(2)°]. In the crystal, multiple N-H?O hydrogen-bond inter-actions are found between the ammonium and sulfate groups.
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2-Amino-6-nitro-1,3-benzothia-zol-3-ium hydrogen sulfate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 07-08-2011
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In the title molecular salt, C(7)H(6)N(3)O(2)S(+)·HSO(4) (-), the 2-amino-6-nitro-1,3-benzothia-zole ring system is essentially planar [mean deviation = 0.0605?(4)?Å]. In the crystal, N-H?O and O-H?O hydrogen-bonding inter-actions result in a layer motif.
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Assessment of groundwater vulnerability in the Yinchuan Plain, Northwest China using OREADIC.
Environ Monit Assess
PUBLISHED: 06-30-2011
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Groundwater vulnerability assessments provide a measure of the sensitivity of groundwater quality to an imposed contaminant load and are globally recognized as an essential element of all aquifer management and protection plans. In this paper, the vulnerability of groundwaters underlying the Yinchuan Plain of Northwest China is determined using OREADIC, a GIS-based assessment tool that incorporates the key characteristics of the universally popular DRASTIC approach to vulnerability assessment but has been modified to consider important additional hydrogeological factors that are specific to the region. The results show that areas of high vulnerability are distributed mainly around Qingtongxia City, Wuzhong City, Lingwu City, and Yongning County and are associated with high rates of aquifer recharge, shallow depths to the water table, and highly permeable aquifer materials. The presence of elevated NO (3) (-) in the high vulnerability areas endorses the OREADIC approach. The vulnerability maps developed in this study have become valuable tools for environmental planning in the region and will be used for predictive management of the groundwater resource.
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5-Azacytidine induces cardiac differentiation of human umbilical cord-derived mesenchymal stem cells by activating extracellular regulated kinase.
Stem Cells Dev.
PUBLISHED: 06-01-2011
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5-Azacytidine (5-Aza) induces differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes. However, the underlying mechanisms are not well understood. Our previous work showed that 5-Aza induces human bone marrow-derived MSCs to differentiate into cardiomyocytes. Here, we demonstrated that 5-Aza induced cardiac differentiation of human umbilical cord-derived MSCs (hucMSCs) and explored the potential signaling pathway. Our results showed that hucMSCs had cardiomyocyte phenotypes after 5-Aza treatment. In addition, myogenic cells differentiated from hucMSCs were positive for mRNA and protein of desmin, ?-myosin heavy chain, cardiac troponin T, A-type natriuretic peptide, and Nkx2.5. Human diploid lung fibroblasts treated with 5-Aza expressed no cardiac-specific genes. 5-Aza did not induce hucMSCs to differentiate into osteoblasts. Further study revealed that 5-Aza treatment activated extracellular signal related kinases (ERK) in hucMSCs, but protein kinase C showed no response to 5-Aza administration. U0126, a specific inhibitor of ERK, could inhibit 5-Aza-induced expression of cardiac-specific genes and proteins in hucMSCs. Increased phosphorylation of signal transducers and activators of transcription 3, and up-regulation of myocyte enhancer-binding factor-2c and myogenic differentiation antigen in 5-Aza-treated hucMSCs were also suppressed by U0126. Taken together, these results suggested that sustained activation of ERK by 5-Aza contributed to the induction of the differentiation of hucMSCs into cardiomyocytes in vitro.
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Mesenchymal stem cells isolated from human uterine cervix cancer tissues.
Cell Biol. Int.
PUBLISHED: 05-04-2011
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In the present study, MSCs (mesenchymal stem cells) were successfully isolated and identified from hUCC (human uterine cervix cancer) tissues. The morphological appearance, immunophenotype, growth curve, cell cycle, cytogenetic features and differentiation potential of these cells were investigated. Results showed that cells isolated from the uterine cervix cancer tissues displayed fibroblast-like morphology and grew into colonies. Immunophenotyping by flow cytometry revealed that the isolated cells were positive for CD13, CD29, CD44, CD105 and HLA-I, while negative for CD10, CD14, CD31, CD34, CD38 and HLA-DR. The cells kept a normal karyotype by chromosome analysis. At the third passage, the percentages of cells in G0-/G1-, 2-/M- and S-phase were 84.94, 8.36 and 6.71%, respectively. Under appropriate induction conditions, these cells can differentiate into osteogenic, adipogenic cells and hepatocytes. Taken together, MSCs were confirmed to exist in hUCC tissues, which may provide a new target for clinical cancer therapy.
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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.

How does it work?

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

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

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