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Find video protocols related to scientific articles indexed in Pubmed.
Development of Organometallic S6K1 Inhibitors.
J. Med. Chem.
PUBLISHED: 10-31-2014
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Aberrant activation of S6 kinase 1 (S6K1) is found in many diseases, including diabetes, aging, and cancer. We developed ATP competitive organometallic kinase inhibitors, EM5 and FL772, which are inspired by the structure of the pan-kinase inhibitor staurosporine, to specifically inhibit S6K1 using a strategy previously used to target other kinases. Biochemical data demonstrate that EM5 and FL772 inhibit the kinase with IC50 value in the low nanomolar range at 100 ?M ATP and that the more potent FL772 compound has a greater than 100-fold specificity over S6K2. The crystal structures of S6K1 bound to staurosporine, EM5, and FL772 reveal that the EM5 and FL772 inhibitors bind in the ATP binding pocket and make S6K1-specific contacts, resulting in changes to the p-loop, ?C helix, and ?D helix when compared to the staurosporine-bound structure. Cellular data reveal that FL772 is able to inhibit S6K phosphorylation in yeast cells. Together, these studies demonstrate that potent, selective, and cell permeable S6K1 inhibitors can be prepared and provide a scaffold for future development of S6K inhibitors with possible therapeutic applications.
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Indole alkaloids with new skeleton activating neural stem cells.
Org. Lett.
PUBLISHED: 10-29-2014
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Alstoscholarisines A-E (1-5), five unprecedented monoterpenoid indole alkaloids with 6/5/6/6/6 fused-bridge rings, were isolated from Alstonia scholaris. They promoted adult neuronal stem cells (NSCs) proliferation significantly, in which the most active one (1) functioned from a concentration of 0.1 ?g/mL in a dosage-dependent manner. Furthermore, 1 enhanced NSC sphere formation and neurogenic fate commitment through activation of a Wnt signaling pathway and promoted NSC differentiation but did not affect proliferation of neuroblastoma cells.
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Apigenin inhibits migration and invasion via modulation of epithelial mesenchymal transition in prostate cancer.
Mol Med Rep
PUBLISHED: 10-01-2014
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The mortality rate associated with prostate cancer is mainly due to metastases rather than primary organ?confined disease. Decreasing the incidence of metastasis is important in treating prostate cancer. 4',5,7?trihydroxyflavone (apigenin) has been demonstrated to be effective in inhibiting several types of cancer. The aim of this study was to investigate the effect and mechanism of apigenin on the movement of prostate cancer cells. In the present study, DU145 cells were treated with varying concentrations of apigenin for different time periods. Cell viability was evaluated using an MTT assay. Cell motility and invasiveness were assayed using wound healing assays and a Matrigel migration and invasion assay. Flow cytometric and western blot analyses were performed to examine the cell cycle and signaling pathways. The results demonstrated that apigenin suppressed the proliferation and inhibited the migration and invasive potential of the DU145 prostate cancer cells in a dose? and time?dependent manner, which was associated with epithelial mesenchymal transition. These findings suggested that apigenin may be effective in treating human prostate cancer.
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Analysis of the difference in the course of the lingual arteries caused by tongue position change.
Laryngoscope
PUBLISHED: 09-06-2014
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To explore the difference in the course of the lingual arteries between the tongue in the fully extended position and in the resting position in obstructive sleep apnea hypopnea syndrome (OSAHS) patients.
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[Combination of phage display and SEREX for screening early lung cancer associated antigens].
Zhejiang Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-05-2014
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To screen out effective lung cancer associated antigens for early diagnosis in order to improve the level of early diagnosis.
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Comparison of anomalous systemic artery to left lower lobe and pulmonary sequestration in left lower lobe by computed tomography.
Acta Radiol
PUBLISHED: 08-28-2014
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Differentiation of anomalous systemic artery to the left lower lobe (ASALLL) from pulmonary sequestration (PS) is essential, as ASALLL can be corrected by anastomosis, embolization, or ligation of the anomalous artery.
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Reduced immunogenicity of induced pluripotent stem cells derived from Sertoli cells.
PLoS ONE
PUBLISHED: 08-28-2014
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Sertoli cells constitute the structural framework in testis and provide an immune-privileged environment for germ cells. Induced pluripotent stem cells (iPS cells) resemble embryonic stem cells (ES cells) and are generated from somatic cells by expression of specific reprogramming transcription factors. Here, we used C57BL/6 (B6) Sertoli cells to generate iPS cells (Ser-iPS cells) and compared the immunogenicity of Ser-iPS cells with iPS cells derived from mouse embryonic fibroblast (MEF-iPS cells). Ser-iPS cells were injected into syngeneic mice to test for their in vivo immunogenicity in teratoma assay. Teratoma assay allows assessing in vivo immunogenicity of iPS cells and of their differentiated progeny simultaneously. We observed that early-passage Ser-iPS cells formed more teratomas with less immune cell infiltration and tissue damage and necrosis than MEF-iPS cells. Differentiating Ser-iPS cells in embryoid bodies (EBs) showed reduced T cell activation potential compared to MEF-iPS cells, which was similar to syngeneic ES cells. However, Ser-iPS cells lost their reduced immunogenicity in vivo after extended passaging in vitro and late-passage Ser-iPS cells exhibited an immunogenicity similar to MEF-iPS cells. These findings indicate that early-passage Ser-iPS cells retain some somatic memory of Sertoli cells that impacts on immunogenicity of iPS cells and iPS cell-derived cells in vivo and in vitro. Our data suggest that immune-privileged Sertoli cells might represent a preferred source for iPS cell generation, if it comes to the use of iPS cell-derived cells for transplantation.
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[The molecular mechanism of interaction of trivalent dimethylarsinous acid (DMA(III)) binding to rat hemoglobin].
Yao Xue Xue Bao
PUBLISHED: 08-26-2014
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In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.
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Cell fusion enhances mesendodermal differentiation of human induced pluripotent stem cells.
Stem Cells Dev.
PUBLISHED: 08-11-2014
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Human induced pluripotent stem cells (iPS cells) resemble embryonic stem cells and can differentiate into cell derivatives of all three germ layers. However, frequently the differentiation efficiency of iPS cells into some lineages is rather poor. Here, we found that fusion of iPS cells with human hematopoietic stem cells (HSCs) enhances iPS cell differentiation. Such iPS hybrids showed a prominent differentiation bias toward hematopoietic lineages but also toward other mesendodermal lineages. Additionally, during differentiation of iPS hybrids, expression of early mesendodermal markers-Brachyury (T), MIX1 Homeobox-Like Protein 1 (MIXL1), and Goosecoid (GSC)-appeared with faster kinetics than in parental iPS cells. Following iPS hybrid differentiation there was a prominent induction of NODAL and inhibition of NODAL signaling blunted mesendodermal differentiation. This indicates that NODAL signaling is critically involved in mesendodermal bias of iPS hybrid differentiation. In summary, we demonstrate that iPS cell fusion with HSCs prominently enhances iPS cell differentiation.
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Limonoid and Steroidal Saponin from Azadirachta indica.
Nat Prod Bioprospect
PUBLISHED: 08-07-2014
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A new limonoid, 17-(5-methoxy-2-oxofuran-3-yl)-28-deoxonimbolide (1), and a new C21 steroidal saponin, 2?,4?-dihydroxy-pregn-5-en-16-one-3?-O-D-glucopyranoside (2), together with 11 known compounds were isolated from the methanol extract of the leaves of Azadirachta indica. The structures were elucidated by means of spectroscopic analysis and putative biosynthetic origins. All the compounds were evaluated for their antibacterial activities against six bacterial strains.
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Identifying the role of microRNAs in spinal cord injury.
Neurol. Sci.
PUBLISHED: 08-06-2014
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Spinal cord injury (SCI) is medically and socioeconomically debilitating, and effective treatments are lacking. The elucidation of the pathophysiological mechanisms underlying SCI is essential for developing effective treatments for SCI. MicroRNAs (miRNAs) are small non-coding RNA molecules (18-24 nucleotides long) that regulate gene expression by interacting with specific target sequences. Recent studies suggest that miRNAs can act as post-transcriptional regulators to inhibit mRNA translation. Bioinformatic analyses indicate that the altered expression of miRNAs has an effect on critical processes of SCI physiopathology, including astrogliosis, oxidative stress, inflammation, apoptosis, and neuroplasticity. Therefore, the study of miRNAs may provide new insights into the molecular mechanisms of SCI. Current studies have also provided potential therapeutic clinical applications that involve targeting mRNAs to treat SCI. This review summarizes the biogenesis and function of miRNAs and the roles of miRNAs in SCI. We also discuss the potential therapeutic applications of miRNA-based interventions for SCI.
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Antimicrobial steroidal saponin and oleanane-type triterpenoid saponins from Paullinia pinnata.
BMC Complement Altern Med
PUBLISHED: 07-25-2014
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Paullinia pinnata L. (Sapindaceae) is an African woody vine, which is widely used in traditional medicine for the treatment of human malaria, erectile dysfunction and bacterial infections. A phytochemical investigation of its methanol leaf and stem extracts led to the isolation of seven compounds which were evaluated for their antimicrobial properties.
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Clinical significance of methylation of E-cadherin and p14ARF gene promoters in skin squamous cell carcinoma tissues.
Int J Clin Exp Med
PUBLISHED: 07-15-2014
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Epigenetic regulation of genes by DNA methylation contributes to cancer. The present study sought to identify methylation changes in the promoters of E-cadherin and p14ARF, two genes with potential cancer roles promoting in skin squamous cell carcinoma. Skin squamous cell carcinoma specimens were collected from 40 patients and normal skin tissues were collected from 30 individuals as controls. Promoter methylation was detected for E-cadherin and p14ARF by methylation-specific PCR. Correlations between E-cadherin or p14ARF methylation and clinicopathological parameters were analyzed by the Spearman rank test. Methylation of E-cadherin (37.5%) and p14ARF (60.0%) was significantly more common in skin squamous cell carcinoma than in normal skin tissue (10.0 and 6.7%, respectively; P < 0.05). Additionally, E-cadherin and p14ARF methylation were positively correlated within skin squamous cell carcinoma (r = 0.422, P = 0.007). Furthermore, methylation of these gene promoters in skin squamous cell carcinoma was correlated with differentiation, lymph node metastasis, and clinical stage (P < 0.05). Aberrant methylation in promoters of E-cadherin and p14ARF may promote occurrence and progression of skin squamous cell carcinoma.
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Quantitative proteomics study of protective effects of grape seed procyanidin B2 on diabetic cardiomyopathy in db/db mice.
Biosci. Biotechnol. Biochem.
PUBLISHED: 06-26-2014
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Diabetic cardiomyopathy is one of the major complications of diabetes mellitus. Oxidative stress appears to play a substantial role in cardiomyopathy. Grape seed procyanidin B2 (GSPB2) has been known as an anti-oxidant in treating diabetes mellitus; however, little is known about its effects and underlying mechanisms on diabetic cardiomyopathy. The present study is to explore the molecular targets of GSPB2 responsible for the anti-oxidative effects in db/db mice by quantitative proteomics. GSPB2 (30?mg/kg body weight/day) were intragastric administrated to db/db mice for 10?weeks. Proteomics of the heart tissue extracts by isobaric tags for relative and absolute quantification analysis was obtained from db/db mice. Our study provides important evidence that GSPB2 protect against cardiomyopathy in diabetes mellitus, which are believed to result from regulating the expression of key proteins involving cardiac fibrosis and proliferation. GSPB2 could be expected to become novel clinical application in fighting against diabetic cardiomyopathy.
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Exploring redox-mediating characteristics of textile dye-bearing microbial fuel cells: thionin and malachite green.
Bioresour. Technol.
PUBLISHED: 05-08-2014
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Prior studies indicated that biodecolorized intermediates of azo dyes could act as electron shuttles to stimulate wastewater decolorization and bioelectricity generation (WD&BG) in microbial fuel cells (MFCs). This study tended to explore whether non-azo textile dyes (i.e., thionin and malachite green) could also own such redox-mediating capabilities for WD&BG. Prior findings mentioned that OH and/or NH2 substitute-containing auxochrome compounds (e.g., 2-aminophenol and 1,2-dihydroxybenzene) could effectively mediate electron transport in MFCs for simultaneous WD&BG. This work clearly suggested that the presence of electron-mediating textile dyes (e.g., thionin and malachite green (MG)) in MFCs is promising to stimulate color removal and bioelectricity generation. That is, using MFCs as operation strategy for wastewater biodecolorization is economically promising in industrial applications due to autocatalytic acceleration of electron-flux for WD&BG in MFCs.
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All-trans retinoic acid induces arginase-1 and inducible nitric oxide synthase-producing dendritic cells with T cell inhibitory function.
J. Immunol.
PUBLISHED: 04-30-2014
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Hepatic stellate cells (HSC) are a major source of the immunoregulatory metabolite all-trans retinoic acid (ATRA), which may contribute to the generation of tolerogenic dendritic cells (DCs) in the liver. The present study seeks to clarify the mechanism(s) through which ATRA promotes the development of tolerogenic DCs. Although bone marrow-derived ATRA-treated DCs (RA-DCs) and conventional DCs had comparable surface phenotype, RA-DCs had diminished stimulatory capacity and could directly inhibit the expansion of DC/OVA-stimulated OT-II T cells. Arginase-1 (Arg-1) was found promote suppression because 1) ATRA was a potent inducer of Arg-1 protein and activity, 2) the Arg-1 inhibitor N(w)-hydroxy nor-l-arginine partially reversed suppression, and 3) the suppressive function of RA-DCs was partially compromised using OT-II T cells from GCN2(-/-) mice, which are insensitive to Arg-1. Inducible NO synthase (iNOS), however, was found to be a more significant contributor to RA-DC function because 1) ATRA potentiated the expression of IFN-?-induced iNOS, 2) suppressive function in RA-DCs was blocked by the iNOS inhibitor N(G)-monomethyl-l-arginine, monoacetate salt, and 3) RA-DCs derived from iNOS(-/-) mice exhibited near complete loss of tolerogenic function, despite sustained Arg-1 activity. The expression of iNOS and the suppressive function of RA-DCs were dependent on both IFN-? and ATRA. Furthermore, the in vivo behavior of RA-DCs proved to be consistent with their in vitro behavior. Thus, we conclude that ATRA enhances both Arg-1 and iNOS expression in IFN-?-treated DCs, resulting in a tolerogenic phenotype. These findings elucidate mechanisms through which ATRA may contribute to liver immune tolerance.
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Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of esophageal cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-26-2014
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Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.
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Nasopharyngeal tube: a simple and effective tool to screen patients indicated for glossopharyngeal surgery.
J Clin Sleep Med
PUBLISHED: 04-16-2014
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The aim of this prospective controlled study was to explore the diagnostic value of repeated polysomnography (PSG) post-nasopharyngeal tube insertion in the setting of glossopharyngeal obstruction in obstructive sleep apnea hypopnea syndrome (OSAHS).
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Catalytic production of cyclic carbonates mediated by lanthanide phenolates under mild conditions.
Chem. Commun. (Camb.)
PUBLISHED: 04-14-2014
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Readily available lanthanide complexes stabilized by a bridged poly(phenolate) ligand have been used for the first time as efficient catalysts for the insertion of CO2 into epoxides to generate cyclic carbonates with high activity, high selectivity, and a wide substrate scope under mild conditions.
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Matrine reduces proliferation of human lung cancer cells by inducing apoptosis and changing miRNA expression profiles.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-11-2014
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Matrine, a main active component extracted from dry roots of Sophora flavecens , has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and time- dependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.
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Chemical Constituents from the Stems of Ecdysanthera rosea.
Nat Prod Bioprospect
PUBLISHED: 04-10-2014
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One new eudesmane sesquiterpenoid (1) named ecdysantherol A and two new benzene derivatives ecdysantherols B (2) and C (3), together with five known benzene derivatives (4-8) were isolated from the stems of Ecdysanthera rosea. The structures of the new compounds were elucidated by extensive spectroscopic methods and X-ray diffraction. The known compounds were identified by the comparison of their spectroscopic data with reported literature data. Compound 1 showed moderate antibacterial activity against the Providensia smartii with MIC value of 12.5 ?g/mL.
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miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.
Molecules
PUBLISHED: 04-02-2014
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The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.
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Antidiabetic and antioxidative effect of jiang tang xiao ke granule in high-fat diet and low-dose streptozotocin induced diabetic rats.
Evid Based Complement Alternat Med
PUBLISHED: 03-28-2014
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Diabetes mellitus (DM), a kind of metabolic disease, is increasing over the last four decades in the world. The purpose of this study was to investigate the effect of Jiang Tang Xiao Ke (JTXK) granule, a naturally occurring ingredient from Chinese herbal medicines, on serum glucose, lipids, and oxidative stress in DM rats induced by high-fat diet and streptozotocin. JTXK granule 9?g/kg (based on crude herb equivalent) and pioglitazone 1.5?mg/kg (as a positive control for comparison) were orally administrated to DM rats for 4 weeks. Results showed that administration of JTXK granule reduced serum glucose, total cholesterol, triglyceride, and low density lipoprotein levels (by 12%, 33%, 57%, and 44%, resp.) but increased high-density lipoprotein level by 69%, compared with the drug-untreated DM rats. Serum malondialdehyde and nitric oxide levels were lowered (by 34% and 52%, resp.) associated with the elevation in serum superoxide dismutase levels (by 60%) after JTXK granule treatment. In addition, JTXK granule suppressed serum alanine aminotransferase activity (up to 50%) and alleviated pathological changes of pancreas and liver tissues in DM rats. The beneficial changes of pioglitazone on biomarkers were also found in DM rats. These findings suggested that JTXK granule may be an alternative medicine for the management of DM.
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Synthesis, crystal structures, and antibacterial evaluation of metal complexes based on functionalized 2-phenylquinoline derivatives.
Acta Chim Slov
PUBLISHED: 03-26-2014
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A series of dinuclear paddle-wheel like transition metal complexes based on 2-phenylquinoline-4-carboxylic derivative L have been synthesized and characterized by IR, elemental analysis, and X-ray diffraction single crystal analysis. The biological activities of L and its complexes were evaluated as assayed antibacterial activities, including Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The results indicated that these complexes showed better antibacterial activities than the free ligand or metal salts alone. Among them, the Zn(II) and Cd(II) complexes with IC50 of 0.57 µg/mL and 0.51 µg/mL, respectively, showed excellent antibacterial activity against Staphylococcus aureus.
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Lingua-epiglottis position predicts glossopharyngeal obstruction in patients with obstructive sleep apnea hypopnea syndrome.
Eur Arch Otorhinolaryngol
PUBLISHED: 03-24-2014
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The objective of the study was to investigate the relationship between lingua-epiglottis position and glossopharyngeal obstruction in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). One hundred and four patients with OSAHS diagnosed by polysomnography (PSG) were enrolled. Lingua-epiglottis position was visualized using endoscopy and classified into three types. Spiral CT imaging of the upper respiratory tract was performed to measure the cross-sectional area and inner diameter of the glossopharyngeal airway. The PSG was repeated after nasopharyngeal tube insertion (NPT-PSG). The NPT-PSG results, CT-measured data and incidence of stenosis were compared among the different lingua-epiglottis position groups. Obstructive sleep apnea hypopnea syndrome patients with different lingua-epiglottis positions had similar demographics. As lingua-epiglottis position type varied from type I to type III, cross-sectional area and inner diameter of the glossopharyngeal area decreased, glossopharyngeal airway stenosis rate increased, and apnea hypopnea index measured by NPT-PSG increased. The lowest oxygen saturation decreased. Lingua-epiglottis position was significantly related to glossopharyngeal obstruction. Lingua-epiglottis position should be used in clinical practice for the preliminary assessment of glossopharyngeal obstruction.
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Deciphering characteristics of bicyclic aromatics--mediators for reductive decolorization and bioelectricity generation.
Bioresour. Technol.
PUBLISHED: 03-21-2014
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This first-attempt study quantitatively assessed electron-mediating characteristics of bicyclic aromatics - 1-amino-2-naphthol, 4-amino-1-naphthol (i.e., decolorized intermediates of azo dyes - orange I and II) for color removal and power generation in MFCs. According to cyclic-voltammetric profiles, the presence of reduction and oxidation peak potentials clearly suggested a crucial role of these intermediates as electron-shuttling mediators. Shake-flask cultures also showed that appropriate accumulation of 1A2N, 4A1N apparently enhanced color-removal efficiencies of bacterial decolorization. This study clearly suggested that suitable supplementation of electrochemically active electron shuttle(s) to dye-bearing MFCs is a promising strategy to stimulate reductive decolorization and bioelectricity generation.
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Cotransplantation with myeloid-derived suppressor cells protects cell transplants: a crucial role of inducible nitric oxide synthase.
Transplantation
PUBLISHED: 03-20-2014
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Islet transplantation is an alternative to pancreas transplantation to cure type 1 diabetes, but both require chronic immunosuppression, which is often accompanied by deleterious side effects. The purpose of this study was to explore prolongation of islet allograft survival by cotransplantation with myeloid-derived suppressor cells (MDSCs) without requirement of immunosuppression and determine the role of inducible nitric oxide synthase (iNOS) produced by MDSCs in immune regulation.
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Enhanced efficacy of combination therapy with adeno?associated virus-delivered pigment epithelium-derived factor and cisplatin in a mouse model of Lewis lung carcinoma.
Mol Med Rep
PUBLISHED: 02-27-2014
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Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis, and the antitumor effect of adeno-associated virus (AAV)-mediated PEDF expression has been demonstrated in a range of animal models. The combined treatment of low-dose chemotherapy and gene therapy inhibits the growth of solid tumors more effectively than current traditional therapies or gene therapy alone. In the present study, the effect of treatment with an AAV2 vector harboring the human PEDF (hPEDF) gene in combination with low-dose cisplatin on the growth of Lewis lung carcinoma (LLC) in mice was assessed. LLC cells were infected with AAV-enhanced green fluorescent protein (EGFP) in the presence or absence of cisplatin, and then the effect of cisplatin on AAV-mediated gene expression was evaluated by image and flow cytometric analysis. Tumor growth, survival time, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD) and apoptotic index were analyzed in C57BL/6 mice treated with AAV-hPEDF, cisplatin or cisplatin plus AAV-hPEDF. The results of the present study provide evidence that cisplatin treatment is able to enhance AAV-mediated gene expression in LLC cells. In addition, the combined treatment of cisplatin plus AAV?hPEDF markedly prolonged the survival time of the mice and inhibited tumor growth, resulting in significant suppression of tumor angiogenesis and induction of tumor apoptosis in vivo, and also protected against cisplatin-related toxicity. These findings suggest that combination of AAV-hPEDF and cisplatin has potential as a novel therapeutic strategy for lung cancer.
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Induction of dedifferentiated male mouse adipose stromal vascular fraction cells to primordial germ cell-like cells.
Cell Biol. Int.
PUBLISHED: 02-25-2014
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The adipose stromal vascular fraction (SVF) contains abundant mesenchymal stem cell populations that have a limited ability to self-renew and differentiate. Male mouse adipose SVF cells were dedifferentiated by reprogramming factors (c-Myc, Oct4, Sox2, and Klf4) to form embryonic stem cell-like cells (ESCLCs), which upgraded their limited differentiation potential. The ESCLCs were induced to differentiate toward epiblast-like cells (EpiLCs) and primordial germ cell-like cells (PGCLCs) by culturing in media supplied with activin A and BMP-4, respectively. The derived ESCLCs possess embryonic stem cell features and can automatically form embryonic bodies. After culture in EpiLC induction medium for 2-3 days, ESCLCs formed flattened epithelial structures that were different from their original water drop-like colonies, and the expression of pluripotency-related genes decreased. When the cells that had been cultured in EpiLC induction medium for 2 days were isolated and cultured in PGCLC induction medium for 4-6 days, they formed typical water drop-like colonies again. Moreover, expression of the pluripotency-related genes and the primordial germ cell (PGC) specification-related genes increased. During progression from ESCLCs toward EpiLCs and PGCLCs, the levels of histone methylases H3K9me2 and H3K27me3 kept changing, which resembled those seen in PGC specification. The derived PGCLCs expressed SSEA-1, Blimp-1, and Stella. Furthermore, methylation of Igf2r and Snrpn was retained, but H19 and Kcnq1ot1 methylation levels were slightly reduced compared to non-PGCLCs, suggesting that the derived PGCLCs may have initiated the process of imprint erasure.
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Expressional difference, distributions of TGF-?1 in TGF-?1 knock down transgenic mouse, and its possible roles in injured spinal cord.
Exp. Biol. Med. (Maywood)
PUBLISHED: 02-17-2014
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Transforming growth factor ?1 (TGF-?1) is a multi-functional cytokine implicated in many aspects of mammalian wound healing and scar tissue formation. However, few experiments have so far addressed the potential biological effects of TGF-?1 in the nervous system after injury, in addition to the immune system. In the present study, expressional silencing TGF-?1 was achieved by selecting predesigning hairpins targeting mouse TGF-?1 genes. Four homozygous transgenic offspring were generated and designed as Founder 90, Founder 12, Founder 41 and Founder 46. The down-regulated rates of TGF-?1 in different transgenic mice were also determined. To investigate the potential roles of TGF-?1, we observed changes in the neurological behavior of TGF-?1-knockdown (TGF-?1-kd) mice after spinal cord transection (SCT). Moreover, mRNA levels of inflammatory cytokines, including IL-1, IL-6, IL-10, NF-?B and TNF, were also detected in nucleate cells from blood by real-time PCR. Consequently, different TGF-?1 expressions were detected in multiple tissues, and protein levels of TGF-?1 decreased at different rates relative to that of wild type (WT) ones. The levels of TGF-?1 proteins in TGF-?1-kd mice decreased at most by 57% in Founder 90, which showed a significant recovery in Basso, Beattie, Bresnahan (BBB) scores after SCT compared with that of WT. However, expressions of immune relative genes showed no dramatic difference compared with WT ones. This study is the first to generate TGF-?1 down regulated mice and determine the possible roles of TGF-?1 in vivo in different conditions.
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The combined treatment of amyloid-?1-42-stimulated bone marrow-derived dendritic cells plus splenocytes from young mice prevents the development of Alzheimer's disease in APPswe/PSENldE9 mice.
Neurobiol. Aging
PUBLISHED: 02-13-2014
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Anti-amyloid-? (A?) immunotherapy is a potential therapeutic strategy to reduce amyloid plaques and amyloid-associated pathologies in Alzheimer's disease (AD). Immune senescence with aging has also played a crucial role in AD pathogenesis and influences the effect of anti-A? immunotherapy. In this study, a combined treatment of A?1-42-bone marrow-derived dendritic cells (BMDCs) with intraperitoneal injection of splenocytes from young mice was designed as a novel immunotherapy for AD in APPswe/PSEN1de9 transgenic mice models. The results showed that the combined treatment not only elevated the level of anti-A? antibodies but also reduced amyloid plaques in brain and finally ameliorated deterioration of spatial learning and memory in AD mice. Additionally, the results revealed an increase of CD68 positive microglial cells in the vicinity of amyloid plaques in the mouse brain, which was responsible for the enhanced phagocytosis of A? plaques. In conclusion, the A?1-42-BMDCs plus splenocytes treatment improved the phagocytosis of microglia and prevented AD pathology more effectively. This combined immunotherapy provided a promising treatment in preventing the progression of AD in clinical studies in the near future.
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Genotype-phenotype correlation in a cohort of paroxysmal kinesigenic dyskinesia cases.
J. Neurol. Sci.
PUBLISHED: 02-07-2014
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Recently, PRRT2 gene mutations have been identified as a causative factor of paroxysmal kinesigenic dyskinesia (PKD). However, evidence is still lacking with respect to the genotype to phenotype correlation in PKD patients.
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Dynamics of interstitial calcium in rat myocardial ischemia reperfusion injury in vivo.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 02-06-2014
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Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury (IR). However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium dynamics in rat myocardial IR model in vivo. A microdialysis system was involved, and the time delay of the system and recovery time was introduced and tested with a fluids switching method. Twelve SD rats were divided into IR or control group. Myocardial IR was induced by ligating (20 min) then releasing (60 min) the suture underlying left anterior descending branch. Mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area for occlusion. Dialysate samples were collected every 10 min. Dialysate calcium concentration was detected with an atomic absorption spectrophotometer. Recovery time for the microdialysis system was 20 min, and recovery rate was 16%. Dialysate calcium concentration showed no changes during ischemia, descended immediately after reperfusion, reached the lowest level (67% of baseline value) 20 min after reperfusion, then escalated slowly. Recovery time was an important parameter for mycrodialysis technique, and it should not be neglected and needed to be tested. Our data suggest that interstitial calcium concentration in rats with myocardial IR in vivo kept steady in ischemia, descended rapidly at the initial reperfusion, then rebounded slowly. In conclusion, we introduced the concept of recovery time for microdialysis and provided a simple testing method.
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Tea consumption and prostate cancer: an updated meta-analysis.
World J Surg Oncol
PUBLISHED: 01-31-2014
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Tea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis.
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Molecular cloning and expression analysis of inhibitor of growth protein 3 (ING3) in the Manila clam, Ruditapes philippinarum.
Mol. Biol. Rep.
PUBLISHED: 01-28-2014
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Inhibitor of growth protein 3 (ING3), a new member of ING family, is involved in the regulation of various processes. In this study, a full-length cDNA of ING3 (named as RpING3) was cloned from the gill of Ruditapes philippinarum by rapid amplification of cDNA ends method for the first time. The cDNA obtained was 1442 bp exclusive of poly (A) residues with a 1248 bp open reading frame encoding 415 amino acids. The RpING3 protein has a calculated molecular weight of 46.59 kDa and isoelectric point of 6.62. Two conserved motif and some functional sites were found. Tissue distribution analysis of the RpING3 mRNA revealed that the RpING3 expression level was much higher in gill and digestive gland while lower in mantle, foot and adductor muscle. The temporal expression of RpING3 in digestive gland after lead exposure was recorded by quantitative real-time PCR. The result showed that RpING3 was rapidly up-regulated at 6 h post-exposure and reached tenfold of the control group. These results suggest that RpING3 dependent signaling pathway is present in Manila clam and RpING3 may play important roles in protecting cells from heavy metal damage in R. philippinarum.
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Observation of the middle intestinal tight junction structure, cloning and studying tissue distribution of the four Claudin genes of the grass carp (Ctenopharyngodon idellus).
Fish Physiol. Biochem.
PUBLISHED: 01-20-2014
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To confirm the existence of the tight junction (TJ) in middle intestine and obtain the genetic information of Claudin-3, Claudin-15a, Claudinb and Claudinc of grass carp, we observed the physical structure of TJ by transmission electron microscopy and cloned the partial cDNAs of the four Claudins using reverse transcriptase PCR technique. The four partial cDNAs consist of 1,261, 490, 776 and 662 bp encoded 131, 150, 195 and 171 amino acids, respectively. Homology analysis showed that the grass carp Claudin shared high homology with other teleost species, especially with Danio rerio and Carassius auratus. Multi-alignments of the four Claudin amino acid sequences have seen the two conserved cysteines existing in the first extracellular loop of Claudin-15a, Claudinb and Claudinc, and the sequence diversity of the four Claudins mainly lies within the C-terminal tails, which usually end with the -Y-V motif, except the -F-V motif in Claudinb. Tissue distributions of the four Claudins were measured by applying quantitative real-time PCR technique. Results showed that Claudin-3 was mainly expressed in liver and middle intestine and Claudinb was ubiquitously expressed with a higher expression in middle intestine while Claudin-15a and Claudinc were mainly expressed in middle intestine. Our study revealed the existence of the TJ in the middle intestinal and obtained the genetic information of Claudin-3, Claudin-15a, Claudinb and Claudinc of grass carp, aiming to found the molecular biology basis for the further study of the intestinal barrier function of grass carp.
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Green tea extract treatment alleviates ocular inflammation in a rat model of endotoxin-induced uveitis.
PLoS ONE
PUBLISHED: 01-01-2014
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Green tea extract (GTE) ingested by rats exerted anti-oxidative activities in various ocular tissues as shown in our previous studies. The present work investigated anti-inflammatory effects of GTE on endotoxin-induced uveitis (EIU). EIU was generated in adult rats by a footpad injection of 1 mg/kg lipopolysaccharide (LPS). Oral administration of GTE (550 mg/kg) was given one, two or four times after LPS injection. Twenty-four hours later, LPS produced severe hyperemia and edema in the iris. Immunocytochemical examinations showed an accumulation of infiltrating cells in the aqueous humor that were immunopositive for cluster of differentiation 43 (CD43) and CD68, markers for leucocytes and macrophages, respectively. Analyses of the aqueous humor showed an increase in pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). GTE treatments improved the clinical manifestations and reduced infiltrating cells and protein exudation in the aqueous humor, which were not observed under half dose of GTE (275 mg/kg). The number of CD68 positive macrophages residing in the iris and ciliary was also reduced. GTE suppressed production of TNF-?, IL-6 and MCP-1 in the aqueous humor, which was associated with a down-regulation of LPS receptor complex subunits, Toll-like receptor 4 (TLR-4) and CD14, and suppression of nuclear factor-kappa Bp65 (NF-?Bp65) in the iris and ciliary body. Our findings show that GTE is a potent anti-inflammatory agent against the inflammation of EIU, and suggest a potential use in treatment of acute uveitis.
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Prevention of postsurgical cauterization-induced peritoneal adhesions by biodegradable and thermosensitive micelles.
J Biomed Nanotechnol
PUBLISHED: 11-26-2013
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Postsurgical peritoneal adhesion is a major concern in clinical practice which causes significant morbidity and mortality. In this study, we investigated the efficacy of biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) micelles in preventing postsurgical cauterization-induced peritoneal adhesion. The biodegradable PEG-PCL-PEG copolymer could form nano-sized micelles in water, which instantly turned into a non-flowing gel at body temperature due to micellar aggregation. Moreover, a novel sidewall and cecum cauterization rat model was developed and the micelles were assigned for adhesion prevention tests. The PEG-PCL-PEG micelles could be administered by an ordinary syringe and provided unrestricted coverage of the cauterized peritoneum. The micelles instantly formed a gel in situ at body temperature and the formed gel could adhere to the cauterized sites as a durable barrier during critical time of adhesion formation. All rats from the control group (n = 10) developed score 5 adhesion, whereas, eight out of ten rats in the micelle-treated group showed no adhesion at all. Besides, cauterization-induced adhesion formation, adhesiveness and degradation of micelles, remesothelization of peritoneum, and restoration of cauterized tissue were investigated in detail. Our results thus indicated that, it was feasible to use biodegradable and injectable thermosensitive PEG-PCL-PEG micelles for prevention of peritoneal adhesions after surgery.
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The supramolecular interaction mediated chiral 1D cyanide-bridged metamagnet: synthesis, crystal structures and magnetic properties.
Dalton Trans
PUBLISHED: 11-25-2013
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Two cyanide-bridged enantiopure one-dimensional single chain complexes, [Mn((R,R)-Salcy)Fe(pcq)(CN)3]2n·1.5nDMF (1) and [Mn((S,S)-Salcy)Fe(pcq)(CN)3]2n·1.5nDMF (2), have been synthesized and structurally characterized. Systematically magnetic investigations show the antiferromagnetic coupling between the cyanide-bridged Mn(iii)-Fe(iii) centers and the interesting metamagnetic behavior at about 5.0 K resulted from the intermolecular ?-? interaction.
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Antibacterial prenylbenzoic acid derivatives from Anodendron formicinum.
Fitoterapia
PUBLISHED: 10-12-2013
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A phytochemical investigation on the stems of Anodendron formicinum led to the isolation of eight prenylbenzoic acid derivatives. Three of these were new compounds, designated as formicinuosides A (1), B (2), and C (3). Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. This is the first report of chemical constituents from A. formicinum and their antimicrobial activities. Among the isolated compounds, compounds 4, 6 and 8 showed significant antibacterial activities against Providensia smartii with MIC values of 0.781?g/mL. Moreover, compound 8 showed remarkable antibacterial activity against Escherichia coli with MIC value of 0.781?g/mL.
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Therapeutic effect of autologous bone marrow-derived liver stem cells transplantation in hepatitis B virus-induced liver cirrhosis.
Hepatogastroenterology
PUBLISHED: 09-26-2013
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To determine the safety, feasibility and therapeutic effect of in vitro-expanded autologous bone marrow-derived liver stem cells (BMDLSC) transplantation in cirrhotic patients following chronic hepatitis B virus infection.
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Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis.
Neurology
PUBLISHED: 09-18-2013
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To perform a meta-analysis on the effect of lowering homocysteine levels via B vitamin supplementation on cerebrovascular disease risk.
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A novel Cs-(129)Xe atomic spin gyroscope with closed-loop Faraday modulation.
Rev Sci Instrum
PUBLISHED: 09-07-2013
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We report a novel Cs-(129)Xe atomic spin gyroscope (ASG) with closed-loop Faraday modulation method. This ASG requires approximately 30 min to start-up and 110 °C to operate. A closed-loop Faraday modulation method for measurement of the optical rotation was used in this ASG. This method uses an additional Faraday modulator to suppress the laser intensity fluctuation and Faraday modulator thermal induced fluctuation. We theoretically and experimentally validate this method in the Cs-(129)Xe ASG and achieved a bias stability of approximately 3.25?°?h.
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Two novel MOF-74 analogs exhibiting unique luminescent selectivity.
Chem. Commun. (Camb.)
PUBLISHED: 08-27-2013
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Two MOF-74 analogs with OH groups on 1D channel surfaces have been synthesized through multi-component self-assembly at room temperature. Their guest-free forms demonstrate a potential luminescent probe or sensor for small molecules, and OH-MOF-74 (2a) also showed exceptional fluorescence quenching and enhancement behavior for different types of aromatic molecules.
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Overexpression of cyclooxygenase-1 correlates with poor prognosis in renal cell carcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-27-2013
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The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognostic value. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative real- time polymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and 91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1 expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 in RCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemical assays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated high expression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p = 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients with high expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. This is the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affected patients.
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Combination of SLC administration and tregs depletion is an attractive strategy for targeting hepatocellular carcinoma.
Mol. Cancer
PUBLISHED: 07-23-2013
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Secondary lymphoid tissue chemokine (SLC) is a key CC chemokine for chemotaxis of immune cells and has been an attractive candidate for anti-tumor treatments. However, among the immune cells recruited by SLC to tumors, the CD25+ Foxp3+ regulatory T cells (Tregs) compromise the anti-tumor effects. In this study, we proposed the combination therapy of intratumoral co-administration of SLC and anti-CD25 monoclonal antibodies (mAbs). We hypothesized that the intratumoral injections of SLC and depletion of Tregs would have stronger inhibition effects for the progression of hepatocellular carcinoma (HCC) in mice.
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A let-7 KRAS rs712 polymorphism increases colorectal cancer risk.
Tumour Biol.
PUBLISHED: 07-19-2013
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Growing evidence has indicated that polymorphism present in the miRNA binding site of target gene can alter the ability of miRNAs to bind its target gene and modulate the development and progression of cancer. We aimed to investigate the association between let-7 KRAS rs712 polymorphism and the risk of colorectal cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study, including 339 CRC patients and 313 age- and sex-matched controls; the relationship between the polymorphism and the clinicopathological features of CRC was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T allele had an increased risk of developing CRC (TT vs. GG, adjusted OR?=?2.18; 95 % CI, 1.00-4.77; T vs. G, adjusted OR?=?1.50; 95 % CI, 1.15-1.96). Stratified analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were more likely to have clinical stage III or IV disease (OR?=?3.29, 95 % CI, 1.32-8.20) and distant metastasis (OR?=?4.70, 95 % CI, 1.81-12.25). These findings provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in the etiology of CRC.
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Functional recovery after transplantation of induced pluripotent stem cells in a rat hemorrhagic stroke model.
Neurosci. Lett.
PUBLISHED: 07-10-2013
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Transplantation of induced pluripotent stem cells (iPSCs) has shown promising therapeutic effects for ischemic stroke. However, it is not clear if this treatment would promote recovery after intracerebral hemorrhage (ICH). In this study, we investigated the functional outcome of iPSCs transplantation in experimental ICH in rats. IPSCs were derived from an ICH patients fibroblasts and were injected into the ipsilateral side of ICH in rats. IPSCs transplantation significantly improved the neurological functions after ICH as compared to vehicle and fibroblast injection. The grafted iPSCs migrated into brain tissue around the hematoma, survived after 4 weeks of transplantation, and exhibited the neural cell-specific biomarkers nestin, ?-tubulin, and GFAP. Immunohistochemical staining showed that the densities of brain derived neurophic factors (BDNF)-positive cells and vascular endothelial growth factor (VEGF)-positive cells were significantly increased around the hemorrhagic brain tissues of iPSCs-treated rats. In addition, iPSCs treatment increased the protein expression of BDNF and VEGF in the surrounding region of hematoma. These findings demonstrate that the transplantation of ICH patient-derived iPSCs contributes toward the improved neurological function in experimental ICH rats. The mechanisms are possibly due to neuronal replacement and enhanced secretion of neurophic factors. Our data suggest that transplantation of ICH patient-derived iPSCs may be a therapeutic strategy for hemorrhagic stroke.
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Homologous recombination-based adenovirus vector system for tumor cell-specific gene delivery.
Cancer Biol. Ther.
PUBLISHED: 06-12-2013
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Cancer gene therapy requires tumor-specific delivery and expression of a transgene to maximize antitumor efficacy and minimize side effects. In this study, we developed a new tumor-targeting, homologous recombination-based adenovirus vector system, HRAVS. HRAVS is composed of two adenovirus vectors, Ad.CMV.IR containing reverse sequence (IR) and a CMV promoter and Ad.IR.EGFP comprising the report gene EGFP and IR. For improved viral DNA replication and transgene expression, the E1a gene was added to HRAVS to generate the enhanced HRAVS, EHRAVS, which consists of Ad.CMV.IR and Ad.IR.EGFP/E1a. The optimal vector composition ratio of Ad.CMV.IR to Ad.IR.EGFP or Ad.IR.EGFP/E1a was identified as 30:70 based on EGFP expression efficiency in tumor cells. The transgene expression of HRAVS and EHRAVS was efficiently and specifically activated in tumor cells only and not in normal cells. Moreover, compared with HRAVS, EHRAVS infection led to higher virus yields and transgene expression and higher toxicity to tumor cells, and these results could be related to the involvement of E1a genes. The results in present study suggest the need for in vivo antitumor study using these new dual-Ad vector systems based on the homologous recombination.
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[Research on quality standards of zhuang medicine Lonicerae dasystylae flos].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 06-04-2013
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To establish quality standard of Zhuang medicine Lonicera dasystyla, and provide scientific basis for the quality control of L. dasystyla.
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Engineering the soil bacterium Pseudomonas putida for arsenic methylation.
Appl. Environ. Microbiol.
PUBLISHED: 05-03-2013
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Accumulation of arsenic has potential health risks through consumption of food. Here, we inserted the arsenite [As(III)] S-adenosylmethionine methyltransferase (ArsM) gene into the chromosome of Pseudomonas putida KT2440. Recombinant bacteria methylate inorganic arsenic into less toxic organoarsenicals. This has the potential for bioremediation of environmental arsenic and reducing arsenic contamination in food.
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Primary pleomorphic rhabdomyosarcoma of the adrenal gland in an adult: A case report.
Oncol Lett
PUBLISHED: 04-10-2013
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A 61-year-old female was referred to The First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, China) due to a right adrenal tumor. A pre-operative transcutaneous fine-needle aspiration biopsy and right adrenalectomy were performed, and pathological analysis resulted in the diagnosis of pleomorphic rhabdomyosarcoma (RMS). Primary pleomorphic RMS of the adrenal gland in an adult is a rare condition. To the best of our knowledge, this is the first case of pleomorphic RMS of the adrenal gland in an adult diagnosed by light microscopy and immunohistochemical stains.
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Promoter-targeted double-stranded small RNAs activate PAWR gene expression in human cancer cells.
Int. J. Biochem. Cell Biol.
PUBLISHED: 03-09-2013
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RNA activation is a promising discovery that promoter-targeted double-stranded small RNAs, termed small activating RNAs (saRNAs), can induce gene expression, which represents a novel approach to gene over-expression without traditional vector-based systems. PAWR is a tumor suppressing gene essential for apoptosis and a cancer-selective target for cancer therapeutics. Here our study identified synthetic saRNAs that could activate the expression of PAWR in human cancer cells. Functional analysis of PAWR induction revealed that saRNA treatment induced growth inhibition and apoptosis of cancer cells, and predictably modulated the expression of known downstream target gene Bcl-2. New functional saRNAs can also be harvested by one or two-base shifting of the original target sites. Chromatin immunoprecipitation assays indicated that activation of PAWR is accompanied by reduced dimethylation at histone H3K9 and increased dimethylation at histone H3K4. Moreover, the existence of transcripts in PAWR promoter was detected but its relationship with RNA activation needs more lucubration. These data have enlarged the gene pool of RNAa and hold great promise as an alternative for PAWR-targeted therapeutics.
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Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells.
Cancer Cell Int.
PUBLISHED: 02-17-2013
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Apigenin (4,5,7-trihydroxyflavone) was recently shown effective in inhibiting several cancers. The aim of this study was to investigate the effect and mechanism of apigenin in the human bladder cancer cell line T24 for the first time.
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Diabetes mellitus and risk of bladder cancer: a meta-analysis of cohort studies.
PLoS ONE
PUBLISHED: 01-31-2013
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Diabetes is associated with increased risk of cancer at several sites, but its association with risk of bladder cancer is still controversial. We examined this association by conducting a systematic review and meta-analysis of cohort studies.
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Transplantation of human neuro-epithelial-like stem cells derived from induced pluripotent stem cells improves neurological function in rats with experimental intracerebral hemorrhage.
Neurosci. Lett.
PUBLISHED: 01-13-2013
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Specific targeted therapy for intracerebral hemorrhage (ICH), which has high disability and case-fatality rate, is currently not available. Induced pluripotent stem cells (iPSCs) generated from somatic cells of ICH patients have therapeutic potential for individualized cerebral protection. While, whether ICH patient-originated iPSCs could differentiate into neuro-epithelial-like stem (NES) cells and whether such NES cells could improve functional recovery in the hemorrhage-injured brain are unclear. Here, we showed that fibroblasts from an ICH patient can be efficiently reprogrammed to iPSCs by lentiviral vectors carrying defined transcription factors (OCT4, SOX2, KLF4, and c-MYC). These iPSCs have the typical morphology, surface antigens, capability of self-renewal and differentiating into cell types of all three embryonic germ layers that are similar to human embryonic stem cells (hESCs). Using defined serum-free neural differentiation medium, we induced the iPSCs differentiate into NES cells. Subsequently, the NES cells from ICH patient-originated iPSCs were transplanted into the perihematoma of rats with experimental ICH injury. Intriguingly, recovery of neurological dysfunction in experimental ICH rats was observed post-NES cells graftage. Transplanted NES cells migrated to the surrounding area of hematoma, survived and differentiated into neuron-like cells. Our study demonstrates that the transplantation of human iPS-originated NES cells is an effective approach of treating ICH injury and the improvement of neural function is partially due to neuronal replacement and regeneration.
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Sesquiterpenoids from Chloranthus multistachys.
Phytochemistry
PUBLISHED: 01-08-2013
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An 8,9-seco-lindenane disesquiterpenoid, chloramultiol G, four eudesmane sesquiterpenoids, ent-(3R)-3-hydroxyatractylenolide III and multistalactones A-C, and four guaiane sesquiterpenoids, (1R,4S,5R,8S,10S)-zedoalactone A and multistalactones D-F, along with 14 known compounds, were isolated from whole plant tissues of Chloranthus multistachys. Their structures were established by extensive NMR experiments in conjunction with mass spectrometry. Except for chloramultiol G, the absolute stereochemistries of the other eight were confirmed by single-crystal X-ray crystallography and CD spectra. Nine compounds were tested for cytotoxicity against five human tumor cell lines and for antifungal activity against four microorganisms in vitro, but all were inactive.
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The role of complement component 3 (C3) in differentiation of myeloid-derived suppressor cells.
Blood
PUBLISHED: 01-08-2013
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Myeloid-derived suppressor cells (MDSCs) play an important role in the regulation of the immune response. MDSC expansion occurs in many circumstances, including cancer, inflammation, stresses, and transplant tolerance. Liver transplants in mice are spontaneously accepted, but hepatocyte transplants are acutely rejected, suggesting the immunoregulatory activities of liver nonparenchymal cells. We have reported that hepatic stellate cells (HpSCs), the stromal cells in the liver, are immensely immunosuppressive and can effectively protect islet transplants via induction of MDSCs. The present study shows that the addition of HpSCs into dendritic cell (DC) culture promoted development of MDSCs, instead of DCs, which was highly dependent on complement component 3 (C3) from HpSCs. The C3(-/-) HpSCs lost their ability to induce MDSCs and, consequently, failed to protect the cotransplanted islet allografts. HpSCs produced complement activation factor B and factor D which then enhanced C3 cleavage to activation products iC3b and C3d. Addition of exogenous iC3b, but not C3d, into the DC culture led to the differentiation of MDSCs with potent immune-inhibitory function. These findings provide novel mechanistic insights into the differentiation of myeloid cells mediated by local tissue cells, and may assist in the development of MDSC-based therapy in clinical settings.
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CCR7 expression and intratumoral FOXP3+ regulatory T cells are correlated with overall survival and lymph node metastasis in gastric cancer.
PLoS ONE
PUBLISHED: 01-01-2013
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The aim of this study was to investigate the prognostic value of chemokine receptor CCR7 expression and intratumoral FOXP3(+) regulatory T cells (Tregs) in gastric cancer. CCR7(+) tumor cells and FOXP3(+) Tregs were assessed by immunohistochemistry in tissue microarrays containing gastric cancer from 133 patients. Prognostic effects of low or high CCR7 and FOXP3 expression were evaluated by Cox regression and Kaplan-Meier analysis, as well as the correlation between CCR7 positive score and intratumoral FOXP3(+) cell number in a longitudinal assessment. The analysis showed that the high expression levels of CCR7 and FOXP3 were detected in 69.9% and 65.4% of cases, respectively. High CCR7 expression in gastric cancer cells was significantly associated with poor overall survival (OS) (P = 0.010) and lymph node metastasis (P = 0.009), and was an independent factor for worse OS (P = 0.023) by multivariate analysis. High numbers of intratumoral FOXP3(+) Tregs significantly correlated with shorter OS (P = 0.021) and lymph node metastasis (P = 0.024), and was also an independent factor for adverse OS (P = 0.035). Furthermore, there was a significantly positive correlation between CCR7 positive score and intratumoral FOXP3(+) cell number (r = 0.949, P<0.001). These results revealed that CCR7 expression in gastric cancer cells and intratumoral FOXP3(+) Tregs could be considered as a co-indicator of clinical prognosis of gastric cancer.
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Depletion of CD4+ CD25+ regulatory T cells promotes CCL21-mediated antitumor immunity.
PLoS ONE
PUBLISHED: 01-01-2013
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CCL21 is known to attract dendritic cells (DCs) and T cells that may reverse tumor-mediated immune suppression. The massive infiltration of tumors by regulatory T cells (Tregs) prevents the development of a successful helper immune response. In this study, we investigated whether elimination of CD4(+) CD25(+) Tregs in the tumor microenvironment using anti-CD25 monoclonal antibodies (mAbs) was capable of enhancing CCL21-mediated antitumor immunity in a mouse hepatocellular carcinoma (HCC) model. We found that CCL21 in combination with anti-CD25 mAbs (PC61) resulted in improved antitumor efficacy and prolonged survival, not only inhibited tumor angiogenesis and cell proliferation, but also led to significant increases in the frequency of CD4(+), CD8(+) T cells and CD11c(+) DCs within the tumor, coincident with marked induction of tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) at the local tumor site. The intratumoral immune responses were accompanied by the enhanced elaboration of IL-12 and IFN-?, but reduced release of the immunosuppressive mediators IL-10 and TGF-?1. The results indicated that depletion of Tregs in the tumor microenvironment could enhance CCL21-mediated antitumor immunity, and CCL21 combined with anti-CD25 mAbs may be a more effective immunotherapy to promote tumor rejection.
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To clone or not to clone? Induced pluripotent stem cells can be generated in bulk culture.
PLoS ONE
PUBLISHED: 01-01-2013
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Induced pluripotent stem cells (iPSCs) are usually clonally derived. The selection of fully reprogrammed cells generally involves picking of individual colonies with morphology similar to embryonic stem cells (ESCs). Given that fully reprogrammed cells are highly proliferative and escape from cellular senescence, it is conceivable that they outgrow non-pluripotent and partially reprogrammed cells during culture expansion without the need of clonal selection. In this study, we have reprogrammed human dermal fibroblasts (HDFs) with episomal plasmid vectors. Colony frequency was higher and size was larger when using murine embryonic fibroblasts (MEFs) as stromal support instead of HDFs or human mesenchymal stromal cells (MSCs). We have then compared iPSCs which were either clonally derived by manual selection of a single colony, or derived from bulk-cultures of all initial colonies. After few passages their morphology, expression of pluripotency markers, and gene expression profiles did not reveal any significant differences. Furthermore, clonally-derived and bulk-cultured iPSCs revealed similar in vitro differentiation potential towards the three germ layers. Therefore, manual selection of individual colonies does not appear to be necessary for the generation of iPSCs - this is of relevance for standardization and automation of cell culture procedures.
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Identification and synthesis of N-(thiophen-2-yl) benzamide derivatives as BRAF(V600E) inhibitors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-01-2013
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The V600E BRAF kinase mutation, which activates the downstream MAPK signaling pathway, commonly occurs in about 8% of all human malignancies and about 50% of all melanomas. In this study, we employed virtual screening and chemical synthesis to identify a series of N-(thiophen-2-yl) benzamide derivatives as potent BRAF(V600E) inhibitors. Structure-activity relationship studies of these derivatives revealed that compounds b40 and b47 are the two most potent BRAF(V600E) inhibitors in this series.
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[Mouse-induced pluripotent stem cells have the potential to differentiate into induced primordial germ cells].
Zhonghua Nan Ke Xue
PUBLISHED: 12-07-2011
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To investigate whether mouse-induced pluripotent stem (iPS) cell line IP14D-1 has the potential to differentiate into induced primordial germ cells (iPGCs), and to explore the changes in the expression of iPGCs-differentiation associated genes and their possible mechanisms.
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Asymmetric hydrogenation of 2- and 2,3-substituted quinoxalines with chiral cationic ruthenium diamine catalysts.
Org. Lett.
PUBLISHED: 11-18-2011
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The enantioselective hydrogenation of 2-alkyl- and 2-aryl-subsituted quinoxalines and 2,3-disubstituted quinoxalines was developed by using the cationic Ru(?(6)-cymene)(monosulfonylated diamine)(BArF) system in high yields with up to 99% ee. The counteranion was found to be critically important for the high enantioselectivity and/or diastereoselectivity.
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Milk consumption and bladder cancer risk: a meta-analysis of published epidemiological studies.
Nutr Cancer
PUBLISHED: 11-01-2011
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Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of milk intake using fixed- or random-effect models depending on the heterogeneity of effects among studies. Nineteen cohort and case-control studies were eligible for inclusion. High milk intake was significantly associated with decreased risk of bladder cancer (OR, 0.84; 95% CI, 0.71-0.97) when comparing the highest with the lowest category of milk intake. The inverse association was stronger in Asia (OR, 0.60; 95% CI, 0.40-0.81) than North America (OR, 0.89; 95% CI, 0.76-1.03), and no association was observed in Europe (OR, 1.05; 95% CI, 0.85-1.26). This relationship also varied significantly by specific dairy products. Our results suggest that milk may be related to the reduction of bladder cancer risk. Further studies need to clarify the biological mechanisms.
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[Effects of di-n-butyl phthalate on the antioxidant enzyme activities and lipid peroxidation level of Perna viridis].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 10-20-2011
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A laboratory experiment was conducted to examine the superoxide dismutase (SOD) and catalase (CAT) activities and the lipid peroxidation (LPO) level presented by malondialdehyde (MDA) in visceral mass and mantle of green mussel (Perna viridis) after exposure to 0.5- 62.5 mg x L(-1) of di-n-butyl phthalate (DBP) for 15 days, and to study the change characteristics of these biochemical indicators after the green mussel released into DBP-free seawater for 10 days. During exposure period, the SOD activity in visceral mass was inhibited first and then reached the level of the control at 0.5 and 2.5 mg x L(-1) of DBP, but inhibited significantly (P< 0.01) at 12.5 and 62.5 mg L(-1) of DBP. The CAT activity in visceral mass was inhibited at all test concentrations of DBP, while the LPO level was obviously induced. During the chronic DBP exposure, the SOD and CAT activities in the mantle were induced significantly but had no regular pattern, and the LPO level was also obviously induced. After the exposed green mussel was released into clean seawater, the SOD and CAT activities in the visceral mass in 12.5 and 62.5 mg DBP x L(-1) groups recovered much slowly, but the LPO level gradually recovered to control level. During the recovery period, the SOD activity in the mantle showed an increasing trend with time, but the CAT activity and LPO level reached gradually to the level of the control.
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A novel vaccine delivery system: biodegradable nanoparticles in thermosensitive hydrogel.
Growth Factors
PUBLISHED: 10-10-2011
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In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature. The in vitro release profile showed that bFGF could be released from bFGF-NPs or bFGF-NPs/hydrogel at an extended period, but the release rate of bFGF-NPs/hydrogel was much lower. In vivo experiments suggested that immunogenicity of bFGF improved significantly after being incorporated into the NPs/hydrogel composite, and strong humoral immunity was maintained for longer than 12 weeks. Furthermore, an in vivo protective anti-tumor immunity assay indicated that immunization with bFGF-NPs/hydrogel could induce significant suppression of the growth and metastases of tumors. Thus, the NPs/hydrogel composite may have great potential application as a novel vaccine delivery system.
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Self-Assembly Pluronic and ?-Cyclodextrin to Hollow Nanospheres for Enhanced Gene Delivery.
Macromol Rapid Commun
PUBLISHED: 07-26-2011
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This paper studies a kind of hollow nanospheres prepared by self-assembly ?-cyclodextrins (?-CDs) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (pluronic F127) for gene delivery. It was found that this kind of hollow nanospheres enable load PEI10K/DNA and the resulting F127?NH(2) ??CD/(PEI10K/DNA) with 0.08?µg/well DNA display equal or higher gene delivery capability compared to PEI10K/DNA with 1?µg/well DNA in the absence or presence of serum. The cytotoxicity of the nanospheres was over 100 times lower than that of PEI10K.
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Formic acid catalyzed gas-phase reaction of H2O with SO3 and the reverse reaction: a theoretical study.
Chemphyschem
PUBLISHED: 07-19-2011
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The formic acid catalyzed gas-phase reaction between H(2)O and SO(3) and its reverse reaction are respectively investigated by means of quantum chemical calculations at the CCSD(T)//B3LYP/cc-pv(T+d)z and CCSD(T)//MP2/aug-cc-pv(T+d)z levels of theory. Remarkably, the activation energy relative to the reactants for the reaction of H(2)O with SO(3) is lowered through formic acid catalysis from 15.97 kcal? mol(-1) to -15.12 and -14.83 kcal? mol(-1) for the formed H(2)O???SO(3) complex plus HCOOH and the formed H(2)O???HCOOH complex plus SO(3), respectively, at the CCSD(T)//MP2/aug-cc-pv(T+d)z level. For the reverse reaction, the energy barrier for decomposition of sulfuric acid is reduced to -3.07 kcal? mol(-1) from 35.82 kcal? mol(-1) with the aid of formic acid. The results show that formic acid plays a strong catalytic role in facilitating the formation and decomposition of sulfuric acid. The rate constant of the SO(3)+H(2)O reaction with formic acid is 10(5) times greater than that of the corresponding reaction with water dimer. The calculated rate constant for the HCOOH+H(2)SO(4) reaction is about 10(-13) cm(3) ?molecule(-1) ?s(-1) in the temperature range 200-280 K. The results of the present investigation show that formic acid plays a crucial role in the cycle between SO(3) and H(2)SO(4) in atmospheric chemistry.
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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.