Phosphoinositide 3-kinase activity leads to silica-induced NF-κB activation through interacting with tyrosine-phosphorylated IκB-α and contributing to tyrosine phosphorylation of p65 NF-κB

The role of the subunits of phosphoinositide (PI) 3-kinase in NF-B activation in silica-stimulated RAW 264.7 cells was investigated. Results indicate that PI3-kinase activity was increased in response to silica. The p85 subunit of PI3-kinase interacted with tyrosine-phosphorylated IB- in silica-stimulated cells. PI3-kinase specific inhibitors, such as wortmannin and LY294003, substantially blocked both silica-induced PI3-kinase and NF-B activation. The inhibition of NF-B activation by PI3-kinase inhibitors was also observed in pervanadate-stimulated but not in LPS-stimulated cells. Furthermore, tyrosine phosphorylation of NF-B p65 was enhanced in cells stimulated with silica, pervanadate or LPS, and wortmannin substantially inhibited the phosphorylation event induced by the first two stimulants but not LPS. Antioxidants, such as superoxide dismutase (SOD), N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), blocked silica-induced PI3-kinase activation, suggesting that reactive oxygen species may be important regulatory molecules in NF-B activation by mediating PI3-kinase activation. Our data suggest that p85 and p110 subunits of PI3-kinase play a role in NF-B activation through interaction with tyrosine-phosphorylated IB- and contributing to tyrosine phosphorylation of p65 NF-B.     

Cell cycle checkpoints and their impact on anticancer therapeutic strategies

Cells contain numerous pathways designed to protect them from the genomic instability or toxicity that can result when their DNA is damaged. The p53 tumor suppressor is particularly important for regulating passage through G1 phase of the cell cycle, while other checkpoint regulators are important for arrest in S and G2 phase. Tumor cells often exhibit defects in these checkpoint proteins, which can lead to hypersensitivity; proteins in this class include ataxia-telangiectasia mutatated (ATM), Meiotic recanbination 11 (Mre11), Nijmegen breakage syndrome 1 (Nbs 1), breast cancer susceptibility genes 1 and 2 (BRCA1), and (BRCA2). Consequently, tumors should be assessed for these specific defects, and specific therapy prescribed that has high probability of inducing response. Tumors defective in p53 are frequently considered resistant to apoptosis, yet this defect also provides an opportunity for targeted therapy. When their DNA is damaged, p53-defective tumor cells preferentially arrest in S or G2 phase where they are susceptible to checkpoint inhibitors such as caffeine and UCN-01. These inhibitors preferentially abrogate cell cycle arrest in p53-defective cells, driving them through a lethal mitosis. Wild type p53 can prevent abrogation of arrest by elevating levels of p21(waf1) and decreasing levels of cyclins A and B. During tumorigenesis, tumor cells frequently loose checkpoint controls and this facilitates the development of the tumor. However, these defects also represent an Achilles heel that can be targeted to improve current therapeutic strategies.     

Cathodic electrochemiluminescence of Ru(bpy)/Nafion coated on graphite oxide electrode in purely aqueous solution

Two cathodic electrochemiluminescence (ECL) peaks have been obtained at ?0.99 and ?1.80 V (vs. SCE), respectively, from Ru(bpy)/Na?on coated onto a graphite oxide electrode in purely aqueous solution under cyclic voltammetric (CV) conditions, without addition of any reducing or oxidative reagents. These two ECL peaks were found to correlate to initial scan direction, pH, and reversal potential. Na?on played an important role in the generation of these two ECL peaks because no cathodic emission was observed in the system without Na?on. It seems that a part of Ru(bpy) electrogenerated at positive potential can remain in the Na?on, even at negative potentials. It was con?rmed that Ru(bpy)⁺ was formed at ?1.80 V by addition of S₂O. The ECL peak at ?0.99 V is attributed to the reaction of Ru(bpy)³⁺ and OH^?. The ECL peak at ?1.80 V is probably due to the annihilation reaction of Ru(bpy)³⁺ and Ru(bpy)⁺. Copyright © 2003 John Wiley & Sons, Ltd.     

Possible role of GH/IGF-1 in the ovarian function of adult hypthyroid rats

We have monitored estrous cycle and measured serum estradiol, GH, IGF-1, T4 and T3 levels in adult hypothyroid female rats which were divided into four groups: H group, hypothyroid rats without treatment; H-T4 group, hypothyroid rats injected daily with T4; HT4-PTU group, hypothyroid rats injected daily with T4 plus PTU (propylthiouracil), and H-T4-IOP group, hypothyroid rats injected daily with T4 plus IOP (iopanoic acid); Euthyroid rats (E group) were used as control. Our results indicate that the lack of sexual cycle in H animals was associated with lower values of estradiol, GH and IGF-1 in comparison to E group; the restoration of sexual cycle in H-T4 group was associated with values of estradiol, GH and IGF-1 higher than those of H group, whereas in H-T4-PTU and H-T4IOP groups the restoration was associated with higher values of GH and IGF-1 and values of estradiol similar to those of H group. These data could suggest a potential role of GH/IGF-1 axis, at least in part, in the lack of sexual cycle in H group and in the ovulation induction in H-T4, H-T4-PTU and H-T4-IOP groups.     

Population database of STRs in West Africa: a genetic study of TPOX, HUMVWA31/A, HUMTH01, and CYP19

Four tetrameric STRs (TPOX, HUMVWA31/A, HUMTH01, and CYP19) were analysed in a West African population (Cabo Verde). No significant deviations from Hardy–Weinberg proportions were observed, either in conventional or exact tests. Pairwise comparisons confirmed allelic independence for all the combinations of loci. Data is provided for the first time about CYP19 in Black populations. In comparisons between African and Afro‐American populations, significant frequency differences for several alleles at the TH01 and VWA31/A loci were observed. The allele frequencies provided in this study contribute to a better knowledge of the variability of these markers among the main human groups, especially in the context of Subsaharan African populations. This revised version was published online in July 2006 with corrections to the Cover Date.     

The catalysis of nucleotide polymerization by compounds of divalent lead

Summary Soluble lead salts and a number of lead-containing minerals catalyze the formation of oligonucleotides from nucleoside 5-phosphorimidazolides. The effectiveness of lead compounds correlates strongly with their solubility. Under optimal conditions we were able to obtain 18% of pentamer and higher oligomers from ImpA. Reactions involving ImpU gave smaller yields.Abbreviations A adenosine - U uridine - Im imidazole - MeIm 1-methyl-imidazole - EDTA ethylenediaminetetraacetic acid - pA adenosine 5-phosphate - pU uridine 5-phosphate - Ap adenosine cyclic 2:3-phosphate - ATP adenosine 5-triphosphate - AppA P₁,P₂-diadenosine 5-diphosphate - pNp (N = A,U) nucleotide 2(3), 5-diphosphate - ImpA adenosine 5-phosphoreimidazolide - ImpU uridine 5-phosphorimidazolide - A ²pA adenylyl-[25]-adenosine - A ³pA adenylyl-[35]-adenosine - pA ²pA 5-phospho-adenylyl-[25]-adenosine - pA ³pA 5-phospho-adenylyl-[35]-adenosine - pUpU 5-phospho-uridylyl-uridine - pApU 5-phospho-adenylyl-uridine - pUpA 5-phospho-uridylyladenine - (pA)n (n, 2,3,4,) oligoadenylates with 5 terminal phosphate - ImpApA 5-phosphorimidazolide of adenylyl adenosine - (pA) ₅₊ pentamer and higher oligoadenylates with 5 terminal phosphate - (Ap)nA (n = 2,3,4) oligoadenylates without terminal phosphates In the following we do not specify the nature of the internucleotide linkageIn the following we do not specify the nature of the internucleotide linkage     

5Fr Heartrail ST01导管在冠心病复杂病变介入治疗中的应用经验

目的:评价5Fr Heartrail ST01导管在冠心病复杂病变介入治疗中的输送支撑作用。方法:连续入选2012年10月至2014年02月南京市第一医院所有冠心病介入治疗过程中使用5Fr Heartrail ST01导管的病例,回顾性分析患者基线特征、病变特征和手术经过及器械成功率。结果:共有33例患者介入术中使用5Fr Heartrail ST01导管,剔除10例并非处理冠状动脉狭窄病变而使用5Fr Heartrail ST01导管的患者,共有23例冠心病患者采用5Fr Heartrail ST01导管增强支撑,协助球囊和/或支架通过病变。5Fr Heartrail ST01导管的器械成功率为86.96%。其中2例器械失败患者采用Tornus穿通导管补救成功;1例改用6F AL 1.0指引导管补救成功。手术成功率为91.30%,1例无法继续配合而手术失败;1例因出现非血流限制性夹层而失败。结论:5Fr Heartrail ST01导管为冠心病复杂病变介入治疗提供优秀的支撑,提高手术成功率。     

Validated methods for the quantification of biologically active constituents of poplar-type propolis

The validation of rapid, low-cost spectrophotometric procedures for the quantification of the three main groups of bioactive substances (flavones and flavonols, flavanones and dihydroflavonols, and total phenolics) in poplar-type propolis has been performed. A spectrophotometric assay based on the formation of an aluminium chloride complex was applied for the quantification of total flavones and flavonols using galangin as standard. Because of the high amount of flavanones and dihydroflavonols in "poplar type" propolis, the introduction of a distinct procedure for their quantification was considered of special significance and the DAB9 colorimetric method was applied for the purpose. Total phenolic content was measured by the Folin-Ciocalteu procedure using a mixture of pinocembrin and galangin as a reference. The procedures were validated using a model mixture of compounds representing the poplar-type propolis composition as found in previous studies. The accuracy (recovery) varied in the range 84-109%, and the relative standard deviation was 0.5-6.2%. The developed spectrophotometric procedures were applied to six poplar type propolis samples. The results were verified independently by a HPLC procedure. The two sets of results agreed satisfactory, as proven by Student's t-test.     

Effect of extraction method on the yield of furanocoumarins from fruits of Archangelica officinalis Hoffm

Optimal conditions for the extraction and analysis of furanocoumarins from fruits of Archangelica officinalis Hoffm. have been determined. The following extraction methods were used: exhaustive extraction in a Soxhlet apparatus, ultrasonication at 25 and 60 degrees C, microwave-assisted solvent extraction in open and closed systems, and accelerated solvent extraction (ASE). In most cases the yields of furanocoumarins were highest using the ASE method. The effects of extracting solvent, temperature and time of extraction using this method were investigated. The highest yield of furanocoumarins by ASE was obtained with methanol at 100-130 degrees C for 10 min. The extraction yields of furanocoumarins from plant material by ultrasonication at 60 degrees C and microwave-assisted solvent extraction in an open system were comparable to the extraction yields obtained in the time- and solvent-consuming exhaustive process involving the Soxhlet apparatus.