INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced b...INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).展开更多
BACKGROUND: Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was re...BACKGROUND: Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was regarded as a poor prognosis sign of SAP, but the pathogenesis of PE in SAP still has not been clarified in the past decade. The purpose of this review is to elucidate the possible pathogenesis of PE in SAP. DATA SOURCES: The English-language literature concerning PE in this review came from the Database of MEDLINE (period of 1991-2005), and the keywords of severe acute pancreatitis and pancreatic encephalopathy were used in the searching. RESULTS: Many factors were involved in the pathogenesis of PE in SAP. Pancreatin activation, excessive release of cytokines and oxygen free radicals, microcirculation abnormalities of hemodynamic disturbance, ET-1/NO ratio, hypoxemia, bacterial infection, water and electrolyte imbalance, and vitamin B1 deficiency participated in the development of PE in SAP. CONCLUSIONS: The pathogenesis of PE in SAP has not yet been fully understood. The development of PE in SAP may be a multi-factor process. To find out the possible inducing factor is essential to the clinical management of PE in SAP.展开更多
高迁移率族蛋白B1(high-mobility group box 1,HMGB1)是一种保守的核蛋白,对维持核小体稳定、DNA重组、复制、修复及转录有重要作用。其可由坏死的细胞被动释放,或在适宜刺激下主动分泌至胞外。近年的研究显示:HMGB1信号的活化与肺损伤...高迁移率族蛋白B1(high-mobility group box 1,HMGB1)是一种保守的核蛋白,对维持核小体稳定、DNA重组、复制、修复及转录有重要作用。其可由坏死的细胞被动释放,或在适宜刺激下主动分泌至胞外。近年的研究显示:HMGB1信号的活化与肺损伤、肺纤维化、肺癌等肺部疾病的发展密切相关,而阻断HMGB1信号可抑制其病理进程,说明HMGB1的抑制对这类疾病有潜在治疗价值。该文就HMGB1在呼吸系统疾病中的作用及其机制作一综述,以期为上述疾病的诊断和治疗提供新的理论依据。展开更多
p34cdc2 and Cyclin B1 are key components of cell cycle controlling machine and are believed to play a fundamental role in gametogenesis. It is also well known that, in scrotal mammals, spermatogenesis depends greatly ...p34cdc2 and Cyclin B1 are key components of cell cycle controlling machine and are believed to play a fundamental role in gametogenesis. It is also well known that, in scrotal mammals, spermatogenesis depends greatly on the maintenance of comparatively low temperature in the scrotum. To investigate whether the expression of cdc2 and Cyclin B1 in spermatogenic cells during spermatogenesis is actually a temperature dependent event, in situ hybridization, Western blotting and immunohistochemistry analysis were used to study the expression of cdc2 and Cyclin B1 in normal and cryptorchid testis. Results showed that the abdominal temperature had no significant influence on the transcription of cdc2 and Cyclin B1 in the spermatogonia and pachytene/diplotene primary spermatocytes, but it blocked the translation of them. Due to the deficiency of p34cdc2 and Cyclin B1, the spermatogonia and pachytene/diplotene primary spermatocytes were unable to form MPF, hence, they couldn’t undergo karyokinesis. The development of primary spermatocytes was arrested at the G2 to M phase transition. We also found that testosterone could regulate the Cyclin B1 expression in spermatogenic cells. Muscular injection of testosterone could recover spermatogenesis in the unilateral scrotal testis which was influenced by the contralateral cryptorchid testis, but it could not salvage the spermatogenesis block in the cryptorchid testis.展开更多
Sphingolipids have been suggested to act as second messengers for an array of cellular signaling activities in plant cells, including stress responses and programmed cell death （PCD）. However, the mechanisms underpi...Sphingolipids have been suggested to act as second messengers for an array of cellular signaling activities in plant cells, including stress responses and programmed cell death （PCD）. However, the mechanisms underpinning these processes are not well understood. Here, we report that an Arabidopsis mutant, fumonisin B1 r_esistant11-1 （/br11-1）, which fails to generate reactive oxygen intermediates （ROIs）, is incapable of initiating PCD when the mutant is challenged by fumonisin B l （FB0, a specific inhibitor of ceramide synthase. Molecular analysis indicated that FBR11 encodes a long-chain base 1 （LCB 1） subunit of serine palmitoyltransferase （SPT）, which catalyzes the first rate-limiting step of de novo sphingolipid synthesis. Mass spectrometric analysis of the sphingolipid concentrations revealed that whereas the fbr11-1 mutation did not affect basal levels of sphingoid bases, the mutant showed attenuated formation of sphingoid bases in response to FBl. By a direct feeding experiment, we show that the free sphingoid bases dihydrosphingosine, phytosphingosine and sphingosine efficiently induce ROI generation followed by cell death. Conversely, ROI generation and cell death induced by dihydrosphingosine were specifically blocked by its phosphorylated form dihydrosphingosine- 1-phosphate in a dosedependent manner, suggesting that the maintenance of homeostasis between a free sphingoid base and its phosphorylated derivative is critical to determining the cell fate. Because alterations of the sphingolipid level occur prior to the ROI production, we propose that the free sphingoid bases are involved in the control of PCD in Arabidopsis, presumably through the regulation of the ROI level upon receiving different developmental or environmental cues.展开更多
Hepatocellular carcinoma(HCC)occurs commonly and with increasing frequency in developing countries,where it also carries an especially grave prognosis.The major risk factor for HCC in these regions is chronic hepatiti...Hepatocellular carcinoma(HCC)occurs commonly and with increasing frequency in developing countries,where it also carries an especially grave prognosis.The major risk factor for HCC in these regions is chronic hepatitis B virus(HBV)infection,although dietary exposure to aflatoxin B1 also plays an important etio-logical role.Prevention of HCC in developing regions is unlikely in the foreseeable future.Although an effec-tive vaccine against HBV is available,the percentage of babies born in developing countries that receive the full course of immunization remains low.Moreover,the usually long interval between infection with HBV and the development of HCC means that 30 to 50 years will elapse before the full effect of the vaccine will be realized.Practical measures to prevent aflatoxin B1 ex-posure are not in place.Serumα-fetoprotein levels are a useful pointer to the diagnosis of HCC in low-income countries,but definitive diagnosis is hampered both by the lack of the sophisticated imaging equipment now available in developed countries and by obstacles to obtaining histological proof.In the majority of patients in low-income regions,the tumor is inoperable by the time the patient presents.Hepatic resection is seldom possible in sub-Saharan Africa,although the tumor is successfully resected in a larger number of patients in China.Liver transplantation for HCC is rarely performed in either region.Sophisticated new radiotherapy tech-niques are not available in developing countries.The beneficial effects of the multikinase inhibitor,sorafenib,are encouraging,although financial considerations may restrict its use in low-income countries.展开更多
OBJECTIVE： To investigate the effects of ophiopogonin D on human breast cancer MCF-7 cells METHODS： Cell viability was assessed by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide and colony formation ...OBJECTIVE： To investigate the effects of ophiopogonin D on human breast cancer MCF-7 cells METHODS： Cell viability was assessed by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide and colony formation experiments. Cell cycle was measured with cell cycle flow cytometry and a living cell assay. Apoptosis and terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling assays were performed to detect the apoptosis of MCF-7 cells induced by ophiopogonin D. Finally, Western blotting was used to explore the mechanism. RESULTS： Exposure of cells to ophiopogonin D resulted in marked decreases in viable cells and colony formation with a dose-dependent manner. Treatment of these cells with ophiopogonin D also resulted in cell cycle arrest at the G2/M phase, and increased apoptosis. Mechanistically, ophiopogonin D-induced G2/M cell cycle arrest was associated with down-regulation of cyclin BI. Furthermore, activation of caspase-8 and caspase-9 was involved in ophiopogonin D-induced apoptosis. CONCLUSION： The data suggested that ophiopogonin D inhibits MCF-7 cell growth via the induction of cell cycle arrest at the G2/M phase.展开更多
The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activator...The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction.展开更多
基金the National Natural Science Foundation of China,No.39260033.
文摘INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).
基金This work was supported by grants from the Technology Foundation of Traditional Chinese Medicine Science of Zhejiang Province (No.2003C130 No.2004C142)+4 种基金the Foundation of Medical Sciences and Technology of Zhejiang Province (No.2003B134)the Grave Foundation for Technological Development of Hangzhou (2003123B19)the Intensive Foundation for Technology of Hangzhou (No.2004Z006)the Foundation for Medical Sciences and Technology of Hangzhou (No.2003A004)the Foundation for Technology of Hangzhou (No.2005224).
文摘BACKGROUND: Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was regarded as a poor prognosis sign of SAP, but the pathogenesis of PE in SAP still has not been clarified in the past decade. The purpose of this review is to elucidate the possible pathogenesis of PE in SAP. DATA SOURCES: The English-language literature concerning PE in this review came from the Database of MEDLINE (period of 1991-2005), and the keywords of severe acute pancreatitis and pancreatic encephalopathy were used in the searching. RESULTS: Many factors were involved in the pathogenesis of PE in SAP. Pancreatin activation, excessive release of cytokines and oxygen free radicals, microcirculation abnormalities of hemodynamic disturbance, ET-1/NO ratio, hypoxemia, bacterial infection, water and electrolyte imbalance, and vitamin B1 deficiency participated in the development of PE in SAP. CONCLUSIONS: The pathogenesis of PE in SAP has not yet been fully understood. The development of PE in SAP may be a multi-factor process. To find out the possible inducing factor is essential to the clinical management of PE in SAP.
文摘高迁移率族蛋白B1(high-mobility group box 1,HMGB1)是一种保守的核蛋白,对维持核小体稳定、DNA重组、复制、修复及转录有重要作用。其可由坏死的细胞被动释放,或在适宜刺激下主动分泌至胞外。近年的研究显示:HMGB1信号的活化与肺损伤、肺纤维化、肺癌等肺部疾病的发展密切相关,而阻断HMGB1信号可抑制其病理进程,说明HMGB1的抑制对这类疾病有潜在治疗价值。该文就HMGB1在呼吸系统疾病中的作用及其机制作一综述,以期为上述疾病的诊断和治疗提供新的理论依据。
基金National Natural Science FOundation of China.Grant! Nos: 39770370, 39630160We are grateful to Dr. A. Koff and Dr. J. Pines f
文摘p34cdc2 and Cyclin B1 are key components of cell cycle controlling machine and are believed to play a fundamental role in gametogenesis. It is also well known that, in scrotal mammals, spermatogenesis depends greatly on the maintenance of comparatively low temperature in the scrotum. To investigate whether the expression of cdc2 and Cyclin B1 in spermatogenic cells during spermatogenesis is actually a temperature dependent event, in situ hybridization, Western blotting and immunohistochemistry analysis were used to study the expression of cdc2 and Cyclin B1 in normal and cryptorchid testis. Results showed that the abdominal temperature had no significant influence on the transcription of cdc2 and Cyclin B1 in the spermatogonia and pachytene/diplotene primary spermatocytes, but it blocked the translation of them. Due to the deficiency of p34cdc2 and Cyclin B1, the spermatogonia and pachytene/diplotene primary spermatocytes were unable to form MPF, hence, they couldn’t undergo karyokinesis. The development of primary spermatocytes was arrested at the G2 to M phase transition. We also found that testosterone could regulate the Cyclin B1 expression in spermatogenic cells. Muscular injection of testosterone could recover spermatogenesis in the unilateral scrotal testis which was influenced by the contralateral cryptorchid testis, but it could not salvage the spermatogenesis block in the cryptorchid testis.
基金Acknowledgments We would like to thank the Arabidopsis Biological Resources Center （Ohio State University, USA） for providing seeds and Dr Teresa Dunn （Uniformed Services University of the Health Sciences, USA） for providing yeast strains. We are grateful to Drs Weicai Yang, Yongbiao Xue （Institute of Genetics and Developmental Biology, Chinese Academy of Sciences） and De Ye （China Agriculture University） for critical reading of the manuscript. This work was supported by grants from the National Natural Science Foundation of China （30330360, 30125025 and 30221002） and the Chinese Academy of Sciences to Jianru Zuo.
文摘Sphingolipids have been suggested to act as second messengers for an array of cellular signaling activities in plant cells, including stress responses and programmed cell death （PCD）. However, the mechanisms underpinning these processes are not well understood. Here, we report that an Arabidopsis mutant, fumonisin B1 r_esistant11-1 （/br11-1）, which fails to generate reactive oxygen intermediates （ROIs）, is incapable of initiating PCD when the mutant is challenged by fumonisin B l （FB0, a specific inhibitor of ceramide synthase. Molecular analysis indicated that FBR11 encodes a long-chain base 1 （LCB 1） subunit of serine palmitoyltransferase （SPT）, which catalyzes the first rate-limiting step of de novo sphingolipid synthesis. Mass spectrometric analysis of the sphingolipid concentrations revealed that whereas the fbr11-1 mutation did not affect basal levels of sphingoid bases, the mutant showed attenuated formation of sphingoid bases in response to FBl. By a direct feeding experiment, we show that the free sphingoid bases dihydrosphingosine, phytosphingosine and sphingosine efficiently induce ROI generation followed by cell death. Conversely, ROI generation and cell death induced by dihydrosphingosine were specifically blocked by its phosphorylated form dihydrosphingosine- 1-phosphate in a dosedependent manner, suggesting that the maintenance of homeostasis between a free sphingoid base and its phosphorylated derivative is critical to determining the cell fate. Because alterations of the sphingolipid level occur prior to the ROI production, we propose that the free sphingoid bases are involved in the control of PCD in Arabidopsis, presumably through the regulation of the ROI level upon receiving different developmental or environmental cues.
文摘Hepatocellular carcinoma(HCC)occurs commonly and with increasing frequency in developing countries,where it also carries an especially grave prognosis.The major risk factor for HCC in these regions is chronic hepatitis B virus(HBV)infection,although dietary exposure to aflatoxin B1 also plays an important etio-logical role.Prevention of HCC in developing regions is unlikely in the foreseeable future.Although an effec-tive vaccine against HBV is available,the percentage of babies born in developing countries that receive the full course of immunization remains low.Moreover,the usually long interval between infection with HBV and the development of HCC means that 30 to 50 years will elapse before the full effect of the vaccine will be realized.Practical measures to prevent aflatoxin B1 ex-posure are not in place.Serumα-fetoprotein levels are a useful pointer to the diagnosis of HCC in low-income countries,but definitive diagnosis is hampered both by the lack of the sophisticated imaging equipment now available in developed countries and by obstacles to obtaining histological proof.In the majority of patients in low-income regions,the tumor is inoperable by the time the patient presents.Hepatic resection is seldom possible in sub-Saharan Africa,although the tumor is successfully resected in a larger number of patients in China.Liver transplantation for HCC is rarely performed in either region.Sophisticated new radiotherapy tech-niques are not available in developing countries.The beneficial effects of the multikinase inhibitor,sorafenib,are encouraging,although financial considerations may restrict its use in low-income countries.
基金Financial assistance was provided by grants from the National Natural Science Foundation of China(No.81173141)
文摘OBJECTIVE： To investigate the effects of ophiopogonin D on human breast cancer MCF-7 cells METHODS： Cell viability was assessed by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide and colony formation experiments. Cell cycle was measured with cell cycle flow cytometry and a living cell assay. Apoptosis and terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling assays were performed to detect the apoptosis of MCF-7 cells induced by ophiopogonin D. Finally, Western blotting was used to explore the mechanism. RESULTS： Exposure of cells to ophiopogonin D resulted in marked decreases in viable cells and colony formation with a dose-dependent manner. Treatment of these cells with ophiopogonin D also resulted in cell cycle arrest at the G2/M phase, and increased apoptosis. Mechanistically, ophiopogonin D-induced G2/M cell cycle arrest was associated with down-regulation of cyclin BI. Furthermore, activation of caspase-8 and caspase-9 was involved in ophiopogonin D-induced apoptosis. CONCLUSION： The data suggested that ophiopogonin D inhibits MCF-7 cell growth via the induction of cell cycle arrest at the G2/M phase.
文摘The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction.
