目的探讨COX-2和surv iv in在B细胞非霍奇金淋巴瘤(B-NHL)中的表达及临床意义。方法采用免疫组化S-P法检测43例B-NHL和10例良性淋巴结病变组织中COX-2和surv iv in的表达。结果COX-2和surv iv in在B-NHL中的阳性表达率分别为55.8%(24/43...目的探讨COX-2和surv iv in在B细胞非霍奇金淋巴瘤(B-NHL)中的表达及临床意义。方法采用免疫组化S-P法检测43例B-NHL和10例良性淋巴结病变组织中COX-2和surv iv in的表达。结果COX-2和surv iv in在B-NHL中的阳性表达率分别为55.8%(24/43)和69.8%(30/43),与对照组相比差异具有显著性(P<0.05)。Ⅲ/Ⅳ期B-NHL患者COX-2蛋白的表达高于Ⅰ/Ⅱ期患者(P<0.05)。surv iv in的表达与B-NHL的组织病理学等级和国际预后指数(IP I)具有相关性(P<0.05)。Spearm an相关分析表明COX-2的表达与surv iv in的表达呈正相关(r=1.000,P=0.030)。结论COX-2和surv iv in在B-NHL中表达上调以及两者之间的阳性表达密切相关,表明COX-2和surv iv in在B-NHL的发生和发展中具有协同作用。展开更多
Aromatic compounds (ACs) in soil can induce competitive inhibition for soil NH3 oxidation, and nitrification inhibitors can be used to this end. A laboratory incubation experiment was performed with 12 nitroaromatic c...Aromatic compounds (ACs) in soil can induce competitive inhibition for soil NH3 oxidation, and nitrification inhibitors can be used to this end. A laboratory incubation experiment was performed with 12 nitroaromatic compounds (NACs), 15 amidoaromatic compounds (AACs) and 20 hydroxyaromatic compounds (HACs) to assess the inhibitory effects of ACs on soil nitrification. Based on these results, the critical and optimal concentrations of ACs were determined for better inhibitory effects. Most of the test ACs were able to inhibit soil nitrification; the effectiveness differed with soil type. Among the ACs, the NACs with m-nitryl, amino or hydroxyl and the AACs with a nitro group or a chlorine atom on aromatic ring or with a p-hydroxyl were more effective. 3-nitroaniline, 4-aminophenol and 3-nitrophenol showed the greatest potential as nitrification inhibitors. The critical concentration of these compounds in brown soil and cinnamon soil was found to be 0.5 mg kg-1 soil. Due to the toxicity, carcinogenicity and mutagenicity of ACs, further toxicological and ecotoxicological research is necessary before ACs are used as nitrification inhibitors in agricultural and horticultural practices.展开更多
Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been...Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been produced and are widely used in clinical treatment. However, because of their flaws in the structure of peptide, the clinical efficacy is limited. In this review, we summarize the structure, pharmacological effects and the potential clinical value of non-peptide SST analogs. We focus on the research and development of non-peptide SST analogs since 1998, and discuss the problems and potential prospects for non-peptide SST analogs. We believe that as more non-peptide somatostatin analogs are successfully developed, the extensive clinical application of SSTs will contribute a great deal to medical science.展开更多
The tumor suppressor p53 is a multifunctional, highly regulated, and promoter-specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling. The mechanisms by which p53 directs...The tumor suppressor p53 is a multifunctional, highly regulated, and promoter-specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling. The mechanisms by which p53 directs a damaged cell down either a cell growth arrest or an apoptotic pathway remain poorly understood. Evidence suggests that the in vivo functions of p53 seem to balance the cell-fate choice with the type and severity of damage that occurs. The concept of antirepression, or inhibition of factors that normally keep p53 at bay, may help explain the physiological mechanisms for p53 activation. These factors also provide novel chemotherapeutic targets for the reactivation of p53 in tumors harboring a wild-type copy of the gene.展开更多
Objective To clarify the actions of somatostatin （SST） on the hepatic fibrogenesis in experimental rats. Methods Seventy five Sprague-Dawley rats were divided into 5 groups at random, including normal control, model...Objective To clarify the actions of somatostatin （SST） on the hepatic fibrogenesis in experimental rats. Methods Seventy five Sprague-Dawley rats were divided into 5 groups at random, including normal control, model control, SST-treated model groups of high, medium and low doses （200 μg·kg^-1·d^-1 , 100μg·kg^ 1 ·d^-1and 50 μg·kg^ 1 ·d^-1, respectively） （ n = 15, in each group）. All rats, except for the normal controls, were injected with 40% carbon tetrachloride （ CCI4 ） subcutaneously for 8 weeks to establish hepatic fibrosis. Meanwhile, rats of SST-treated model groups were given different doses of SST twice a day in the same way. Then the liver function, serum levels of hyaluronic acid （HA）, laminin （ LM） , and collagen type IV （CIV） were tested. The collagen types I and III, and pathological changes in liver tissue were assessed. Results Being compared with the model control group, SST-treated groups, especially the medium and low dose ones, exhibited significantly improved indices of liver function, including alanine minotransferase （ALT）, aspartate aminotrans- ferase （AST）, albumin （ALB）, total bilirubin （TBIL） and alkaline phosphatase （ALP）. Markedly lowered expres- sion of serum HA, LM and tissular collagen types I, III were also detected radioimmunologically and immunohisto- chemically in the low dose SST-treated model group. Moreover, pathological findings, such as lessened fibrous septa, decreased hepatic stellate cells （HSCs）, alleviated hepatic steatosis and attenuated inflammation, confirmed the significant improvement in fibrotic degree under the treatment of low dose rather than other doses of SST. Conclusion SST exerts the negative modulatory effect on hepatic fibrosis with a pathophysiological basis of extra- cellular matrixes （ECM） decreasing and hepatocyte protection. Low dose of SST （50 μg·kg^ 1 ·d^-1 ） maY be the optimum one among all doses.展开更多
Gamma-aminobutyric acid(GABA) contributes substantially to neurocognitive function as an important inhibitory neurotransmitter in the human cerebral cortex. However, the pathophysiology of disorders such as epilepsy a...Gamma-aminobutyric acid(GABA) contributes substantially to neurocognitive function as an important inhibitory neurotransmitter in the human cerebral cortex. However, the pathophysiology of disorders such as epilepsy are not well understood, since GABA agonists are not quite effective in treating epilepsy. Knowledge of the mechanism of action of GABA would contribute to review previously proposed anti-epileptic processes by GABA agonists. In this study based on recent experiments on GABAergic astrocytes, we developed a modified GABAergic astrocyte model, and successfully simulated a long-lasting Ca^(2+) oscillation in astrocytes after 0.5-s stimulation of GABAergic transmission. We then incorporated this GABAergic astrocyte model into a classical Ullah-Schiff seizure model and surprisingly found that this GABAergic astrocyte model functions to hinder the anti-epileptic action of GABA agonists, thereby explaining their low efficiency in previous experiments. These results also update our knowledge of the mechanism of action of GABA and the effects of astrocytes on physiological and pathological functions of the brain.展开更多
RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP ki...RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP kinase can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is a good protein substrate for calcineurin. In addition, we found that unphosphorylated RCANI noncompetitively inhibits calcineurin protein phosphatase activity and that the phosphorylation of RCAN1 by p38a MAP kinase decreases the binding affinity of RCAN1 for calcineurin. These findings reveal the molecular mechanism by which p38a MAP kinase regulates the function of RCAN1/calcineurin through phosphorylation.展开更多
文摘目的探讨COX-2和surv iv in在B细胞非霍奇金淋巴瘤(B-NHL)中的表达及临床意义。方法采用免疫组化S-P法检测43例B-NHL和10例良性淋巴结病变组织中COX-2和surv iv in的表达。结果COX-2和surv iv in在B-NHL中的阳性表达率分别为55.8%(24/43)和69.8%(30/43),与对照组相比差异具有显著性(P<0.05)。Ⅲ/Ⅳ期B-NHL患者COX-2蛋白的表达高于Ⅰ/Ⅱ期患者(P<0.05)。surv iv in的表达与B-NHL的组织病理学等级和国际预后指数(IP I)具有相关性(P<0.05)。Spearm an相关分析表明COX-2的表达与surv iv in的表达呈正相关(r=1.000,P=0.030)。结论COX-2和surv iv in在B-NHL中表达上调以及两者之间的阳性表达密切相关,表明COX-2和surv iv in在B-NHL的发生和发展中具有协同作用。
基金Supported by the National Basic Research Program (973 Program) of China (No.2007CB109307)the National Science & Technology Pillar Program (No.2006BAD10B01)
文摘Aromatic compounds (ACs) in soil can induce competitive inhibition for soil NH3 oxidation, and nitrification inhibitors can be used to this end. A laboratory incubation experiment was performed with 12 nitroaromatic compounds (NACs), 15 amidoaromatic compounds (AACs) and 20 hydroxyaromatic compounds (HACs) to assess the inhibitory effects of ACs on soil nitrification. Based on these results, the critical and optimal concentrations of ACs were determined for better inhibitory effects. Most of the test ACs were able to inhibit soil nitrification; the effectiveness differed with soil type. Among the ACs, the NACs with m-nitryl, amino or hydroxyl and the AACs with a nitro group or a chlorine atom on aromatic ring or with a p-hydroxyl were more effective. 3-nitroaniline, 4-aminophenol and 3-nitrophenol showed the greatest potential as nitrification inhibitors. The critical concentration of these compounds in brown soil and cinnamon soil was found to be 0.5 mg kg-1 soil. Due to the toxicity, carcinogenicity and mutagenicity of ACs, further toxicological and ecotoxicological research is necessary before ACs are used as nitrification inhibitors in agricultural and horticultural practices.
文摘Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been produced and are widely used in clinical treatment. However, because of their flaws in the structure of peptide, the clinical efficacy is limited. In this review, we summarize the structure, pharmacological effects and the potential clinical value of non-peptide SST analogs. We focus on the research and development of non-peptide SST analogs since 1998, and discuss the problems and potential prospects for non-peptide SST analogs. We believe that as more non-peptide somatostatin analogs are successfully developed, the extensive clinical application of SSTs will contribute a great deal to medical science.
文摘The tumor suppressor p53 is a multifunctional, highly regulated, and promoter-specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling. The mechanisms by which p53 directs a damaged cell down either a cell growth arrest or an apoptotic pathway remain poorly understood. Evidence suggests that the in vivo functions of p53 seem to balance the cell-fate choice with the type and severity of damage that occurs. The concept of antirepression, or inhibition of factors that normally keep p53 at bay, may help explain the physiological mechanisms for p53 activation. These factors also provide novel chemotherapeutic targets for the reactivation of p53 in tumors harboring a wild-type copy of the gene.
基金Supported by Scientific Development Programs of Science and Technology Commission of Shanghai(004119047)
文摘Objective To clarify the actions of somatostatin （SST） on the hepatic fibrogenesis in experimental rats. Methods Seventy five Sprague-Dawley rats were divided into 5 groups at random, including normal control, model control, SST-treated model groups of high, medium and low doses （200 μg·kg^-1·d^-1 , 100μg·kg^ 1 ·d^-1and 50 μg·kg^ 1 ·d^-1, respectively） （ n = 15, in each group）. All rats, except for the normal controls, were injected with 40% carbon tetrachloride （ CCI4 ） subcutaneously for 8 weeks to establish hepatic fibrosis. Meanwhile, rats of SST-treated model groups were given different doses of SST twice a day in the same way. Then the liver function, serum levels of hyaluronic acid （HA）, laminin （ LM） , and collagen type IV （CIV） were tested. The collagen types I and III, and pathological changes in liver tissue were assessed. Results Being compared with the model control group, SST-treated groups, especially the medium and low dose ones, exhibited significantly improved indices of liver function, including alanine minotransferase （ALT）, aspartate aminotrans- ferase （AST）, albumin （ALB）, total bilirubin （TBIL） and alkaline phosphatase （ALP）. Markedly lowered expres- sion of serum HA, LM and tissular collagen types I, III were also detected radioimmunologically and immunohisto- chemically in the low dose SST-treated model group. Moreover, pathological findings, such as lessened fibrous septa, decreased hepatic stellate cells （HSCs）, alleviated hepatic steatosis and attenuated inflammation, confirmed the significant improvement in fibrotic degree under the treatment of low dose rather than other doses of SST. Conclusion SST exerts the negative modulatory effect on hepatic fibrosis with a pathophysiological basis of extra- cellular matrixes （ECM） decreasing and hepatocyte protection. Low dose of SST （50 μg·kg^ 1 ·d^-1 ） maY be the optimum one among all doses.
基金supported by the National Natural Science Foundation of China(Grant No.11472202)
文摘Gamma-aminobutyric acid(GABA) contributes substantially to neurocognitive function as an important inhibitory neurotransmitter in the human cerebral cortex. However, the pathophysiology of disorders such as epilepsy are not well understood, since GABA agonists are not quite effective in treating epilepsy. Knowledge of the mechanism of action of GABA would contribute to review previously proposed anti-epileptic processes by GABA agonists. In this study based on recent experiments on GABAergic astrocytes, we developed a modified GABAergic astrocyte model, and successfully simulated a long-lasting Ca^(2+) oscillation in astrocytes after 0.5-s stimulation of GABAergic transmission. We then incorporated this GABAergic astrocyte model into a classical Ullah-Schiff seizure model and surprisingly found that this GABAergic astrocyte model functions to hinder the anti-epileptic action of GABA agonists, thereby explaining their low efficiency in previous experiments. These results also update our knowledge of the mechanism of action of GABA and the effects of astrocytes on physiological and pathological functions of the brain.
基金supported in part by Ministry of Science and Technology of China (Grant 2011CB910803)
文摘RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP kinase can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is a good protein substrate for calcineurin. In addition, we found that unphosphorylated RCANI noncompetitively inhibits calcineurin protein phosphatase activity and that the phosphorylation of RCAN1 by p38a MAP kinase decreases the binding affinity of RCAN1 for calcineurin. These findings reveal the molecular mechanism by which p38a MAP kinase regulates the function of RCAN1/calcineurin through phosphorylation.
