Yan Zhang
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Pubmed
Journal: Journal of hazardous materials
January/7/2016
Abstract
In this study, we provide a seed-induced solvothermal method to grow various TiO2 nanostructures on the surfaces of g-C3N4, such as 0D nanoparticles, 1D nanowires 2D nanosheets and 3D mesoporous nanocrystals. We show that the "seeding" endows g-C3N4 with anchoring sites toward the heterogeneous nucleation growth of TiO2, and the distribution of the loaded TiO2 can be controlled by tuning the amount of nucleation in the dispersion. Among synthesized nanostructures, seed-grown Meso-TiO2/g-C3N4 hybrids exhibit the highest photocatalytic activity upon visible light irradiation using methyl orange and phenol as probe organics, which are about 2-4 times and 29-37 times as high as those of direct-grown Meso-TiO2/g-C3N4 without seeding and bare g-C3N4 for degradation of MO and phenol, respectively. The enhancement of photocatalysis can be ascribed to the adequate separation of photogenerated electrons at the heterojunction interfaces and dominant contribution of photoinduced holes mainly caused by the well-constructed nano- architectures.
Pubmed
Journal: Annals of human genetics
April/26/2015
Abstract
T-helper cells that produce IL-17 (Th17 cells) are a subset of CD4(+) T-cells with pathological roles in autoimmune diseases including systemic lupus erythematosus (SLE), and ETS1 is a negative regulator of Th17 cell differentiation. Our previous work on genome-wide association study (GWAS) identified two variants in the ETS1 gene (rs10893872 and rs1128334) as being associated with SLE. However, like many other risk alleles for complex diseases, little is known on how these genetic variants might affect disease pathogenesis. In this study, we examined serum IL-17 levels from 283 SLE cases and observed a significant correlation between risk variants in ETS1 and serum IL-17 concentration in patients, which suggests a potential mechanistic link between these variants and the disease. Furthermore, we found that the two variants act synergistically in influencing IL-17 production, with evidence of significant genetic interaction between them as well as higher correlation between the haplotype formed by the risk alleles and IL-17 level in patient serum. In addition, the correlation between ETS1 variants and IL-17 level seems to be more significant in SLE patients manifesting renal involvement, dsDNA autoantibody production or early-onset.
Pubmed
Journal: Plant molecular biology
April/26/2009
Abstract
To investigate the possible mechanisms of glutathione reductase (GR) in protecting against oxidative stress, we obtained transgenic tobacco (Nicotiana tabacum) plants with 30-70% decreased GR activity by using a gene encoding tobacco chloroplastic GR for the RNAi construct. We investigated the responses of wild type and transgenic plants to oxidative stress induced by application of methyl viologen in vivo. Analyses of CO(2) assimilation, maximal efficiency of photosystem II photochemistry, leaf bleaching, and oxidative damage to lipids demonstrated that transgenic plants exhibited enhanced sensitivity to oxidative stress. Under oxidative stress, there was a greater decrease in reduced to oxidized glutathione ratio but a greater increase in reduced glutathione in transgenic plants than in wild type plants. In addition, transgenic plants showed a greater decrease in reduced ascorbate and reduced to oxidized ascorbate ratio than wild type plants. However, there were neither differences in the levels of NADP and NADPH and in the total foliar activities of monodehydroascorbate reductase and dehydroascorbate reductase between wild type and transgenic plant. MV treatment induced an increase in the activities of GR, ascorbate peroxidase, superoxide dismutase, and catalase. Furthermore, accumulation of H(2)O(2) in chloroplasts was observed in transgenic plants but not in wild type plants. Our results suggest that capacity for regeneration of glutathione by GR plays an important role in protecting against oxidative stress by maintaining ascorbate pool and ascorbate redox state.
Pubmed
Journal: Cellular and molecular life sciences : CMLS
September/15/2017
Abstract
When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique-Particle Image Velocimetry (PIV)-we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A particle-based compass (PBC) model suggests cellular interplay (which depends on cell-cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.
Pubmed
Journal: Methods in molecular biology (Clifton, N.J.)
March/18/2009
Abstract
In recent years, immunochromatographic lateral flow test strips are used as a popular diagnostic tool. There are two formats (noncompetitive and competitive) in gold-based immunoassay. Noncompetitive gold-based immunoassay also called sandwich assay is applied for the detection of large molecular mass. For small molecular mass such as pesticide, competitive format of lateral flow colloidal gold-based immunoassay is described in this chapter. The preparation of gold colloidal and the conjugation between antibody and gold colloidal are described. Hi-flow plus nitrocellulose membranes are separately coated with goat anti-rabbit IgG (control line) and hapten-OVA conjugate (test line). Thus, the degree of intensity of color of the test line is the reverse of the concentration of pesticide in the sample and the visual result is immediately observable. Colloidal gold-based immunoassay can also be applied for multianalysis in one test strip if the detected targets show different physico-chemical properties and their haptens show great differences in chemical structure.
Pubmed
Journal: Journal of thoracic imaging
June/18/2012
Abstract
OBJECTIVE
The purpose of this study was to track and investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction in swine assessed by magnetic resonance imaging (MRI).
METHODS
Twenty-four Chinese mini-pigs (27±3 kg) were divided into 4 groups, including control groups (groups 1 and 3) and MSCs transplantation groups (group 2, super paramagnetic iron oxide labeled and group 4, 4',6-diamidino-2-phenylindole labeled). Super paramagnetic iron oxide-labeled and 4',6-diamidino-2-phenylindole-labeled MSCs (3.0×10⁶ cells/mL) with a volume of 10 mL were injected into the left anterior descending artery by a catheter at 1 week after acute myocardial infarction, respectively. Cell distribution, cardiac functions, and scar tissue were quantitatively assessed by MRI.
RESULTS
The reduction of the T2* value in the myocardium, spleen, and liver in group 2 was significantly greater than that in group 1. MRI showed that function and scar size at baseline and 3 days after cell infusion were not significantly different between groups 1 and 2. Six weeks later left ventricular ejection fraction (P<0.0001), end-systolic volume (P<0.05), the number of dyskinetic segments (P<0.0001), left ventricular weight index (P<0.0001), and the infarcted size (P<0.0001) in group 4 were all improved comparing with those in group 3.
CONCLUSIONS
The majority of MSCs entrapped by the extracardial organs were mainly in the spleen. Catheter-based delivery of autologous bone marrow-derived MSCs into infarcted myocardium is feasible and effective.
Pubmed
Journal: Optics letters
January/13/2009
Abstract
We proposed a novel architecture for optical image encryption based on interference. The encryption algorithm for this new method is quite simple and does not need iterative encoding. The parameters of the configuration can also serve as additional keys for encryption. Numerical simulation results demonstrate the flexibility of this new proposed method.
Pubmed
Journal: Journal of molecular modeling
October/18/2015
Abstract
Biopharmaceuticals are proteins with a crucial role in the treatment of many diseases. However, these protein medicines are often thermally labile and therefore unsuitable for long-term application and storage, as they tend to lose their activity under ambient conditions. Desiccation is one approach to improving protein stability, but the drying process itself can cause irreversible damage. In the current study, insulin was chosen as an example of a thermally sensitive biopharmaceutical to investigate whether the disaccharide, trehalose, can prevent loss of structural integrity due to drying. The experiment was performed using replica exchange molecular simulation and Gromacs software with a Gromos96 (53a6) force field. The results indicate that trehalose preserves the bioactive structure of insulin during drying, consistent with the use of trehalose as a protectant for thermally sensitive biopharmaceuticals. For instance, at the water content of 1.77%, insulin without any protectants yields the highest RMSD value as 0.451 nm, then the RMSD of insulin in presence of trehalose only ca. 0.100 nm.
Pubmed
Journal: Pharmaceutical biology
February/29/2016
Abstract
BACKGROUND
Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], shows neuroprotective and anti-inflammatory effects in vivo and in vitro.
OBJECTIVE
We hypothesized that MLB might exert antidepressant-like effects by targeting the neuroinflammatory signals.
METHODS
Sprague-Dawley rats were subjected to the chronic unpredictable stress (CUS) protocol. Rats in the control group received no CUS during the whole experiment. In the model group, rats were exposed to CUS for 7 weeks. From the beginning of the 5th week, model group rats were randomly grouped and subjected to different treatments. In the experiment, control and model group rats were intraperitoneally (i.p.) injected with saline. MLB was dissolved in saline to give a final concentration, and the rats were injected (i.p.) with 15, 30, or 60 mg/kg MLB once a day for 3 weeks.
RESULTS
MLB administration significantly reduced: (1) the immobility time in the forced swimming test (19 s, p < 0.05); (2) the immobility time in the tail suspension test (76.3 s, p < 0.05); (3) the corticosterone (CORT) concentrations in the serum (21.7 nmol/L, p > 0.05); (4) the pro-inflammatory cytokine levels in the serum - TNF-α (92.1 pg/ml, p < 0.05), IL-1β (86.9 pg/ml, p < 0.05), and IL-6 (93.8 pg/ml, p < 0.05); (5) pro-inflammatory cytokine levels in tissue - TNF-α (3.2 pg/mg protein, p < 0.05), IL-1β (1.5 pg/mg protein, p > 0.05), and IL-6 (6.3 pg/mg protein, p < 0.05); and (6) phospho-NF-κB (1.6, p < 0.05) and phospho-IκB-α (0.4, p < 0.05) expression in tissue.
CONCLUSIONS
The results suggested that MLB might exert therapeutic actions on depression-like behavior and the HPA axis hyperactivity in CUS rats, and the mechanisms underlying the antidepressant-like effects of MLB might be mediated by regulation of the expression of NF-κB and IκB-α in rats.
Pubmed
Journal: Experimental eye research
September/19/2005
Abstract
We previously found that activation of purinergic receptors mobilizes Ca2+ and enhances bicarbonate transport in bovine corneal endothelial cells (BCEC). Since transient receptor potential channel 4 (TRPC) has been reported to be a candidate for capacitative calcium entry (CCE) and receptor operated calcium entry (ROC), we examined the expression of TRPC4 and evaluated the potential involvement of TRPC4 in CCE or ROC in BCEC. The C-terminus of TRPC4 was fused into the glutathione S-transferase (GST) expression vector. The fusion protein GST-TRPC4c was induced in bacteria and purified by affinity chromatography. An antibody was raised in rabbit by using the purified GST-TRPC4c antigen. In Western blotting, the TRPC4 antibody recognized the fusion protein while the pre-immune IgG did not. The TRPC4 antibody recognized a band at around 80 kD for membrane proteins from both the fresh and cultured BCEC. The pre-immune IgG could not detect bands at the same size. Incubation with the TRPC4c antigen abolished the 80 kD band. Immunofluorescence using the TRPC4 antibody stained both fresh and cultured BCEC, while pre-immune IgG did not. RNAi knocked down the expression of TRPC4 in cultured BCEC. Ca2+ entry induced by the purinergic receptor agonist ATP, was increased in TRPC4-siRNA transfected cells compared with the scrambled siRNA control, while Ca2+ entry induced by store depletion through blocking the endoplasmic reticulum Ca2+ pump, did not differ between the siRNA and scrambled siRNA-treated cells. Taken together, these results show that TRPC4 protein is expressed in the bovine corneal endothelial cells and may be a negative regulator in ROC stimulated by purinergic activation, but not by store depletion itself.
Pubmed
Journal: Acta oto-laryngologica
December/12/2016
Abstract
OBJECTIVE
To investigate the relationship between hearing loss and vestibular dysfunction in patients with sudden sensorineural hearing loss (SSHL).
METHODS
Clinical data including the symptom of vertigo of 149 SSHL patients were investigated retrospectively. Pure tone audiometry, ocular vestibular-evoked myogenic potential (oVEMP) and cervical vestibular-evoked myogenic potential (cVEMP) evoked by air-conducted sound (ACS), and caloric test were employed for cochlear and vestibular function assessment. The relationship between hearing level and vestibular dysfunction was analyzed.
RESULTS
The pure tone averages (PTAs) (mean ± SD) of SSHL patients with and without vertigo were 88.81 ± 21.74 dB HL and 72.49 ± 21.88 dB HL (Z = -4.411, p = 0.000), respectively. The PTAs of SSHL patients with abnormal and normal caloric test were 84.71 ± 22.54 dB HL and 70.41 ± 24.07 dB HL (t = -2.665, p = 0.009), respectively. Conversely, vertigo and abnormal caloric results also happened more frequently in patients with profound hearing loss. However, no consistent tendency could be found among vestibular evoked myogenic potentials (VEMPs) responses or hearing loss.
CONCLUSIONS
SSHL patients with vertigo or abnormal caloric test displayed worse hearing loss; and vice versa, vertigo and abnormal caloric results happened more frequently in SSHL patients with profound hearing loss.
Pubmed
Journal: Journal of immunology (Baltimore, Md. : 1950)
November/5/2013
Abstract
Neutrophils are critically involved in host defense and inflammatory injury. However, intrinsic signaling mechanisms controlling neutrophil recruitment and activities are poorly defined. In this article, we showed that protein kinase AKT1 (also known as PKBα) is the dominant isoform expressed in neutrophils and is downregulated upon bacterial infection and neutrophil activation. AKT1 deficiency resulted in severe disease progression accompanied by recruitment of neutrophils and enhanced bactericidal activity in the acute inflammatory lung injury (ALI) and the Staphylococcus aureus infection mouse models. Moreover, the depletion of neutrophils efficiently reversed the aggravated inflammatory response, but adoptive transfer of AKT1(-/-) neutrophils could potentiate the inflammatory immunity, indicating an intrinsic effect of the neutrophil in modulating inflammation in AKT1(-/-) mice. In the ALI model, the infiltration of neutrophils into the inflammatory site was associated with enhanced migration capacity, whereas inflammatory stimuli could promote neutrophil apoptosis. In accordance with these findings, neutralization of CXCR2 attenuated neutrophil infiltration and delayed the occurrence of inflammation. Finally, the enhanced bactericidal activity and inflammatory immunity of AKT-deficient neutrophils were mediated by a STAT1-dependent, but not a mammalian target of rapamycin-dependent, pathway. Thus, our findings indicated that the AKT1-STAT1 signaling axis negatively regulates neutrophil recruitment and activation in ALI and S. aureus infection in mice.
Pubmed
Journal: Journal of cellular biochemistry
December/12/2002
Abstract
The rapid synthesis of heat shock proteins (Hsps) in cells subjected to environmental challenge is controlled by heat shock transcription factor-1 (Hsf1). Regulation of Hsps by Hsf1 is highly complex and, in the whole organism, remains largely unexplored. In this study, we have used mouse embryo fibroblasts and bone marrow progenitor cells from hsf1-/- mice as well as hsp70.3-lacZ knock-in mice bred on the hsf1deficient genetic background (hsf1-/--hsp70.3+/--lacZ), to further elucidate the function of Hsf1 and its participation as a transcriptional activator of Hsp70 synthesis under normal or heat-induced stress conditions in vitro and in vivo. The results revealed that heat-induced Hsp70 expression in mouse tissue is entirely controlled by Hsf1, whereas its activity is not required for tissue-specific constitutive Hsp70 expression. We further demonstrate that Hsf1 is critical for maintaining cellular integrity after heat stress and that cells from hsf1-/- mice lack the ability to develop thermotolerance. This deficiency is explained by the elimination of stress-inducible Hsp70 and Hsp25 response in the absence of Hsf1 activity, leading to a lack of Hsp-mediated inhibition of apoptotic cell death via both caspase-dependent and caspase-independent pathways. The pivotal role of the Hsf1 transactivator in regulating rapid synthesis of Hsps as a critical cellular defense mechanism against environmental stress-induced damage is underlined.
Pubmed
Journal: Zhonghua xin xue guan bing za zhi
August/12/2009
Abstract
OBJECTIVE
To evaluate the therapeutic effects of stem cell transplantation in heart failure patients with old myocardial infarction (OMI) by MRI.
METHODS
Heart failure patients [NYHA 2.7 +/- 0.7, male = 18, mean age (59.5 +/- 10.1) y] with OMI were randomly divided into 2 groups (group A: CABG + stem cell transplantation, group B: CABG; n = 10 each). Left ventricular (LV) function was measured by MRI, viable myocardium was detected by (18)F-FDG myocardial metabolism imaging and late contrast-enhanced at baseline and 6 months post intervention.
RESULTS
LVEF and LVEDV at baseline for group A were (20.71 +/- 6.09)% and (172.73 +/- 32.74) ml, and for group B were (27.59 +/- 2.31)% and (155.13 +/- 28.36) ml, respectively (P > 0.05). The LVEF was equally improved in group A and B (mean 8.63% vs. 10.37%, P > 0.05) while DeltaLVEDV was significant higher in group A than that in group B [(9.91 +/- 39.50) ml vs. (-22.34 +/- 31.35) ml, P < 0.05]. Ventricular wall thickening ratio at 6 months post intervention was significantly higher in group A than that in group B [(11.40 +/- 11.53)% vs. (2.27 +/- 7.20)%, P < 0.05]. Late contrast-enhanced MRI results correlated with (18)F-FDG myocardial metabolism imaging SPECT well in assessment of myocardial viability (kappa value: 0.446, P < 0.001; sensitivity: 68.3% and specificity: 92.5%).
CONCLUSIONS
Stem cell therapy on top of CABG aggravated LV remodeling in heart failure patients with old myocardial infarction. The specificity of MRI is similar to (18)F-FDG SPECT while the sensitivity is inferior to (18)F-FDG SPECT on detecting viable myocardium.
Pubmed
Journal: Analytical and bioanalytical chemistry
July/21/2016
Abstract
We report the design and fabrication of a new type of nanohybrid microelectrode based on a hierarchical nanostructured Au/MnO2/graphene-modified carbon fiber (CF) via in situ electrochemical synthesis, which leads to better structural integration of different building blocks into the CF microelectrode. Our finding demonstrates that wrapping CF with graphene nanosheets has dramatically increased the surface area and electrical conductivity of the CF microelectrode. The subsequent template-free electrodeposition of MnO2 on graphene-wrapped CF gives rise to a porous nanonest architecture built up from twisted and intersectant MnO2 nanowires, which serves as an ideal substrate for the direct growth of Au nanoparticles. Owing to the structural merit and synergy effect between different components, the hierarchical nanostructured noble metal/metal oxide/graphene-coated CF demonstrates dramatically enhanced electrocatalytic activity. When used for nonenzymatic H2O2 sensing, the resultant modified microelectrode exhibits acceptable sensitivity, reproducibility, stability, and selectivity, which enable it to be used for real-time tracking H2O2 secretion in human cervical cancer cells. Graphical abstract A schematic illustration of preparation of hierarchical Au/MnO2/ERGO/CF nanohybrid electrode for real-time molecular detection of cancer cells.
Pubmed
Journal: Neuroreport
July/14/2008
Abstract
Identical comparison stimuli were induced to be recognized as schematic faces or the figures with three English letters 'O' (EngO) by verbal bias and two different contextual priming conditions. Our findings confirmed that there might be a coarse visual categorization around 40-100 ms at mid-parietal site. Larger P1 responses to schematic faces compared with EngO definitely revealed that P1 at occipito-temporal sites should be thought to represent an earlier face-specific processing stage, as early as around 100-120 ms after stimulus onset rather than simply reflect the low-level visual difference. A significant difference of N170/vertex positive potential between the identical comparison stimuli reinforced the evidence that they were early markers of face processing and corroborated the unequivocal influence of contextual effect.
Pubmed
Journal: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
June/1/2011
Abstract
Coagulation factor IX/coagulation factor X binding protein from the venom of Agkistrodon halys Pallas (AHP IX/X-bp) is a unique coagulation factor IX/coagulation factor X binding protein (IX/X-bp). Among all IX/X-bps identified, only AHP IX/X-bp is a Ca(2+)- and Zn(2+)-binding protein. The binding properties of Ca(2+) and Zn(2+) ions binding to apo-AHP IX/X-bp and their effects on the stability of the protein have been investigated by isothermal titration calorimetry, fluorescence spectroscopy, and differential scanning calorimetry. The results show that AHP IX/X-bp has two metal binding sites, one specific for Ca(2+) with lower affinity for Zn(2+) and one specific for Zn(2+) with lower affinity for Ca(2+). The bindings of Ca(2+) and Zn(2+) in the two sites are entropy- and enthalpy-driven. The binding affinity of AHP IX/X-bp for Zn(2+) is 1 order of magnitude higher than for Ca(2+) for either high-affinity binding or low-affinity binding, which accounts for the existence of one Zn(2+) in the purified AHP IX/X-bp. Guanidine hydrochloride (GdnHCl)-induced and thermally induced denaturations of Ca(2+)-Ca(2+)-AHP IX/X-bp, Zn(2+)-Zn(2+)-AHP IX/X-bp, and Ca(2+)-Zn(2+)-AHP IX/X-bp are all a two-state processes with no detectable intermediate state(s), indicating the Ca(2+)/Zn(2+)-induced tight packing of the protein. Ca(2+) and Zn(2+) increase the structural stability of AHP IX/X-bp against GdnHCl or thermal denaturation to a similar extent. Although Ca(2+) and Zn(2+) have no obvious effect on the secondary structure of AHP IX/X-bp, they induce different rearrangements in local conformation. The Zn(2+)-stabilized specific conformation of AHP IX/X-bp may be helpful to its recognition of the structure of coagulation factor IX. This work suggests that in vitro, Ca(2+) plays a structural rather than an active role in the anticoagulation of AHP IX/X-bp, whereas Zn(2+) plays both structural and active roles in the anticoagulation. In blood, Ca(2+) binds to AHP IX/X-bp and stabilizes its structure, whereas Zn(2+) cannot bind to AHP IX/X-bp owing to the low Zn(2+) concentration. AHP IX/X-bp prolongs the clotting time in vivo through its binding only with coagulation factor X/activated coagulation factor X.
Pubmed
Journal: Molecular biology reports
July/11/2012
Abstract
As transient expression systems are effective methods for the functional characterization of genes, a transient gene expression and silencing system was developed for Betula platyphylla Suk (Chinese Birch). Firstly, the cinnamoyl-CoA reductase (CCR) gene and its promoter were isolated from Chinese Birch. The vectors for overexpression of CCR and RNAi-based silence of CCR were constructed and transformed into Agrobacterium, respectively. Overexpression and silence of the CCR gene were respectively, performed on Birch seedlings using an Agrobacterium-mediated transient expression system. The expression levels of CCR were determined using real-time PCR. The results showed that the transcripts of CCR notably increased in the Birch plants transformed with the CCR overexpression construct, and notably decreased in plants transformed with the silencing construct when compared with nontransgenic plants. These studies confirmed that this transient genetic transformation system works well on Birch plants, and can be used for the functional characterization of genes and protein production in Birch.
Pubmed
Journal: Fitoterapia
April/20/2015
Abstract
Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM.
Pubmed
Journal: Bioorganic & medicinal chemistry
September/7/2005
Abstract
The synthesis and evaluation of 10-methanesulfonyl-DDACTHF (1), 10-methanesulfonyl-5-DACTHF (2), and 10-methylthio-DDACTHF (3) as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are reported. The compounds 10-methanesulfonyl-DDACTHF (1, K(i) = 0.23 microM), 10-methanesulfonyl-5-DACTHF (2, K(i) = 0.58 microM), and 10-methylthio-DDACTHF (3, K(i) = 0.25 microM) were found to be selective and potent inhibitors of recombinant human GAR Tfase. Of these, 3 exhibited exceptionally potent, purine sensitive growth inhibition activity (3, IC50 = 100 nM) against the CCRF-CEM cell line being 3-fold more potent than Lometrexol and 30-fold more potent than the parent, unsubstituted DDACTHF, whereas 1 and 2 exhibited more modest growth inhibition activity (1, IC50 = 1.0 microM and 2, IC50 = 2.0 microM).
Pubmed
Journal: Zhongguo shi yan xue ye xue za zhi
December/17/2007
Abstract
Loss of transforming growth factor (TGF)-beta signaling has been implicated in malignant transformation of various tissues. Smad4 plays a central role in the signal transduction of TGF-beta. Deletion or mutation of Smad4 has been described in a number of cancers. This study was aimed to investigate a potential role of Smad4 in leukemia including its expression and location in blast cells. The mononuclear cells were separated from bone marrow of leukemia patients. The samples, blast cells of which were more than 90% in mononuclear cells, were selected. The expression and location of Smad4 protein were analyzed by immunohistochemistry methods. The results showed that the Smad4 protein located mainly in nucleus, part of this protein located in cytoplasma, the expressions of Smad4 were not detected in 6 out of 9 ALL patients, in 7 out of 24 AML patients and in 1 out of 2 CML patients; these leukemia patients, in whose cells the expression of Smad4 was not detected, included one L1 and one L3, four L2, one M0, one M1, two M2a, one M3a, one M4b, one M6 and one CML. In conclusion, the Smad4 protein was mainly in nucleus, the deletion or functional change of Smad4 may related with the pathogenesis of human AML.
Pubmed
Journal: Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology
August/9/2004
Abstract
OBJECTIVE
To explore the countermeasure to reduce fatality in patients with intrathoracic oesophageal perforation caused by foreign body.
METHODS
Exploratory pleuracotomy were operated on all the 12 cases with intrathoracic esophageal perforation caused by foreign body. According to the different pathological morbids, one of following surgical procedures was operated: 1. esophagoscopy was used to fetch the foreign body and the oesophageal perforation was repaired (3 cases), 2. esophagotomy was adopted to fetch the foreign body and to had the oesophageal a drainage using "T" tube (5 cases), 3. esophagotomy was adopted to fetch the foreign body and to had the oesophageal a drainage using "T" tube as well jejunostomy (3 cases). Occlusive drainage were used on all the cases and pleuroclysis with flagyl soloution and normal saline were used on some cases.
RESULTS
Four of 12 cases (33.3%) were cured, the others (66.7%) died, among them 7 cases died of breaks of thoracaorta and hematorrhoea afterwards.
CONCLUSIONS
An esophagoscopy to fetch the foreign body, the pleuracotomy to protect thoracaorta in time, preventing infection and hematorrhoea post-operation are keys in reduce the fatality in patients with intrathoracic oesophageal perforation caused by foreign body.
Pubmed
Journal: Applied and environmental microbiology
March/27/2002
Abstract
Neurospora crassa osmosensitive (os) mutants are sensitive to high osmolarity and therefore are unable to grow on medium containing 4% NaCl. We found that os-2 and os-5 mutants were resistant to the phenylpyrrole fungicides fludioxonil and fenpiclonil. To understand the relationship between osmoregulation and fungicide resistance, we cloned the os-2 gene by using sib selection. os-2 encodes a putative mitogen-activated protein (MAP) kinase homologous to HOG1 and can complement the osmosensitive phenotype of a Saccharomyces cerevisiae hog1 mutant. We sequenced three os-2 alleles and found that all of them were null with either frameshift or nonsense point mutations. An os-2 gene replacement mutant also was generated and was sensitive to high osmolarity and resistant to phenylpyrrole fungicides. Conversely, os-2 mutants transformed with the wild-type os-2 gene could grow on media containing 4% NaCl and were sensitive to phenylpyrrole fungicides. Fludioxonil stimulated intracellular glycerol accumulation in wild-type strains but not in os-2 mutants. Fludioxonil also caused wild-type conidia and hyphal cells to swell and burst. These results suggest that the hyperosmotic stress response pathway of N. crassa is the target of phenylpyrrole fungicides and that fungicidal effects may result from a hyperactive os-2 MAP kinase pathway.
Pubmed
Journal: PloS one
August/31/2016
Abstract
Ewing sarcoma (ES) is the second most common malignant bone and soft tissue tumor in children and adolescents. Despite advances in comprehensive treatment, patients with ES metastases still suffer poor outcomes, thus, emphasizing the need for detailed genetic profiles of ES patients to identify suitable molecular biomarkers for improved prognosis and development of effective and targeted therapies. In this study, the next generation sequencing Ion AmpliSeq™ Cancer Hotspot Panel v2 was used to identify cancer-related gene mutations in the tissue samples from 20 ES patients. This platform targeted 207 amplicons of 2800 loci in 50 cancer-related genes. Among the 20 tissue specimens, 62 nonsynonymous hotspot mutations were identified in 26 cancer-related genes, revealing the molecular heterogeneity of ES. Among these, five novel mutations in cancer-related genes (KDR, STK11, MLH1, KRAS, and PTPN11) were detected in ES, and these mutations were confirmed with traditional Sanger sequencing. ES patients with KDR, STK11, and MLH1 mutations had higher Ki-67 proliferation indices than the ES patients lacking such mutations. Notably, more than half of the ES patients harbored one or two possible 'druggable' mutations that have been previously linked to a clinical cancer treatment option. Our results provided the foundation to not only elucidate possible mechanisms involved in ES pathogenesis but also indicated the utility of Ion Torrent sequencing as a sensitive and cost-effective tool to screen key oncogenes and tumor suppressors in order to develop personalized therapy for ES patients.
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