The G-quadruplexes formed from G-rich strands in the telomere and oncogene-promoter regions are regarded as new promising targets in the cancer therapy.A G-quadruplex in the downstream flanking region of the signal transducer and activator of transcription 3（STAT3） gene was explored.Its folding patterns were proposed to be 3：2：2 and 3：3：1 loop isomers by the mutation analysis by CD spectroscopy.The structures were constructed and refined by molecular modeling method.
Background Central nervous system leukemia （CNSL） is an important relapse in children with acute lymphoblastic leukemia （ALL）. We investigated the possible role of endogenous hydrogen sulfide （H2S） of cerebrospinal fluid （CSF） in predicting CNSL. Methods From August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group （7 cases）, a leukemia group （307 cases）, a non-leukemia group （26 cases） and a healthy group （40 children）. CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H2S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction （RT-PCR）, and H2S levels in serum were also measured. The receiver operating characteristic （ROC） curve and area under curve （AUC） were used to assess the predictive diagnosis role of CSF H2S in children with ALL and CNSL. Results The serum H2S contents of the CNSL and leukemia groups were （96.98±15.77） pmol/L and （93.35±17.16） μmol/L respectively, much higher than those of healthy, （44.29±2.15） pmol/L, and non-leukemia, （46.32±6.54） μmol/L, groups （P 〈0.01）. Compared with the leukemia group, CSF H2S content of the CNSL group was significantly high （P 〈0.01）. Meanwhile, in contrast to the non-leukemia group, CSF H2S contents of the CNSL and leukemia groups were both significantly increased （P 〈0.01）. In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 （95% CI： 0.857-1.000）, and the optimum cut-off value of CSF H2S was 12.08μmol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively. Conclusions CSF H2S contents were significantly increased in children with CNSL. Afte
DU Shu-xuXIAO JiangGUAN FengSUN Li-mingWU Wan-shuiTANG HongDU Jun-baoTANG Chao-shuJIN Hong-fang
Background Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation. Methods Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na＋-K＋-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student＇s ttest for two groups or analysis of variances （ANOVA） for multiple groups were used to compare the differences of the changes. Results Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta-mercaptopyruvate also increased mean arterial pressure （P 〈0.01）, whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure （P 〈0.01）. Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and di
REN Yong-shengWU Sheng-yingWANG Xing-junYU FangZHAO JingTANG Chao-shuOUYANG Jing-pingGENG Bin
目的:利用心肌肥大病理过程中基因表达谱的变化,构建基因/蛋白质调控网络。方法:以苯肾上腺素诱导新生大鼠心肌细胞肥大为模型,在分析肥大心肌细胞基因表达谱变化的基础上,进一步利用Pathwaystudio和Agilent Literature Search软件结合文献挖掘方法,构建基因/蛋白质相互作用网络。结果:构建的网络包含450个相互作用的基因/蛋白质(节点)以及592个它们之间相互作用的关系(边)。拓扑分析表明该网络具有无尺度特性,同时分析确定14个基因/蛋白质是网络的关键节点。通过GO(gene ontology)分析,发现在苯肾上腺素诱导新生大鼠心肌细胞肥大的过程中,与物质代谢、细胞信号转导及细胞骨架等密切相关的基因可能发挥了重要作用。结论:构建基因/蛋白质网络为研究心肌肥大的分子机制提供了有用的信息和方法。
Objective To review the vasorelaxant effects of hydrogen sulfide （H2S） in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved. Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms ＂hydrogen sulfide＂ and ＂vascular relaxation＂. Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected. Results H2S plays an important role in the regulation of cardiovascular tone. The vasomodulatory effects of H2S depend on factors including concentration, species and tissue type. The H2S donor, sodium hydrosulfide （NariS）, causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner. This effect was more pronounced than that observed in pulmonary arterial rings. The expression of KATp channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings. H2S is involved in the pathogenesis of a variety of cardiovascular diseases. Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases. The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the Cr/HCO3 exchanger. It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation. Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.
