Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC...Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.展开更多
Vascular endothelial cell growth inhibitor （VEGI） is a member of the tumor necrosis factor superfamily and plays an important role in vascular homeostasis. In this study, to investigate the anticancer therapeutic po...Vascular endothelial cell growth inhibitor （VEGI） is a member of the tumor necrosis factor superfamily and plays an important role in vascular homeostasis. In this study, to investigate the anticancer therapeutic potential of this gene, a secreted isoform of VEGI （VEGI-251） was inserted into a selectively replicating adenovirus with E1B 55 kDa gene deletion （ZD55） to construct ZD55-VEGI-251. We report here that secreted VEGI-251 produced from ZD55- VEGI-251-infected cancer cells potently inhibits endothelial cell proliferation, tube formation in vitro and angiogen- esis of chick chorioallantoic membrane in vivo. Additionally, ZD55-VEGI-251 infection leads to a much more severe cytopathic effect than control viruses on several human cancer cell lines, including cervical cancer cell line HeLa, hepatoma cell line SMMC-7721 and colorectal cancer cell line SW620. Further study reveals that the increased cytotoxicity is a result of VEGI-251 autocrine-dependent, mitochondria-mediated apoptosis accompanied by caspase-9 activation, enhanced caspase-3 activation and PARP cleavage. Moreover, ZD55-VEGI-251-treatment of athymic nude mice bearing human cervical and colorectal tumor xenografts markedly suppressed tumor growth. Our findings indicate that the combined effect of antiangiogenesis and apoptosis-induction activity makes the VEGI-251-armed oncolytic adenovirus a promising therapeutic agent for cancer.展开更多
The aim of this study was to determine the effects of antioxidants,including α-ketoacids （α-ketoglutarate and pyruvate）,lactate and glutamate/malate combination,against oxidative stress on rat spermatozoa. Our res...The aim of this study was to determine the effects of antioxidants,including α-ketoacids （α-ketoglutarate and pyruvate）,lactate and glutamate/malate combination,against oxidative stress on rat spermatozoa. Our results showed that H2O2 （250 μmol L^-1）-induced damages,such as impaired motility,adenosine triphosphate （ATP） depletion,inhibition of sperm protein phosphorylation,reduced acrosome reaction and decreased viability,could be significantly prevented by incubation of the spermatozoa with α-ketoglutarate （4 mmol L^-1） or pyruvate （4 mmol L^-1）. Without exogenous H2O2 in the medium,the addition of pyruvate （4 mmol L^-1） significantly increased the superoxide anion （O2^-·） level in sperm suspension （P≤0.01）,whereas the addition of α-ketoglutarate （4 mmol L^-1） and lactate （4 mmol L^-1） significantly enhanced tyrosine-phosphorylated proteins with the size of 95 kDa （P≤0.04）. At the same time,α-ketoglutarate,pyruvate,lactate,glutamate and malate supplemented in media can be used as important energy sources and supply ATP for sperm motility. In conclusion,the present results show that α-ketoacids could be effective antioxidants for protecting rat spermatozoa from H2O2 attack and could be effective components to improve the antioxidant capacity ofBiggers,Whitten and Whittingham media.展开更多
AIM:To investigate the acetylcholinesterase（AChE）expression involved in retina pigment epithelial（RPE）apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 ...AIM:To investigate the acetylcholinesterase（AChE）expression involved in retina pigment epithelial（RPE）apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 was from ATCC（Rockville,MD）.Cultured ARPE-19 cells were treated with H2O2 at 0,250,500,1000,2 000μmol/L and cell viability was measured with MTT assay.AChE expression and DNA fragments were analyzed by immunocytochemistry,TUNEL and PARP-1Western blotting.RESULTS:Immunofluorescence detected AChE exist in the normal human retinal tissue.When H2O2】500μmol/L,AChE expression showed an increase after 2h,and this concentration was selected for the present study.RPE cell was induced with 1 000μmoI/L H2O2 for 2h,compared to the control group,cell activity decline detected by MTT,AChE and PARP-1 protein expression was significantly increased detected by Western blotting.AChE immunofluorescence staining was positive in RPE cell after HO2 incubate 2h.In addition,pretreatment with100|jmol/L epigallocatechin gallate（EGCG）,cell viability increased from 31.20%±3.90%to 70.23%±12.96%.CONCLUSION:AChE is weakly expressed in normal human RPE cells.Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells,which may indicate that AChE may be an important role in AMD.展开更多
The author affiliations were mixed up in the previous published version. The third fund number of National NaturalScience Foundation of China in the Acknowledgments was wrong, it should be "30270335". The Sh...The author affiliations were mixed up in the previous published version. The third fund number of National NaturalScience Foundation of China in the Acknowledgments was wrong, it should be "30270335". The Shanghai MunicipalCouncil for Science and Technology (No.06DZ22032) was missed in the Acknowledgments. There are some labelingand production errors in Figure 2A, Figure 3B and 3C, Figure 5C, Figure 6B and 6E, Figure 7B and 7D. In Figure 2A,left panel "A431" should be "Par3". In Figure 3B and 3C, "anti-Par3CT" should be "anti-Par3LCT", "GST-Par3CT"should be "GST-Par3LCT". In Figure 5C, the second arrow indicating "Lamin B" should be "[3-tubulin". In Figure 6Bright panel, the molecular weight for ?-actin should be "43" instead of"200". In Figure 6E, "Par3" should be "Par3i". Themolecular weight for the DNA-PKcs panel should be the same as the p-DNA-PKcs. In Figure 7B, the time point "240"in the left panel should be "120"; in the right panel of Figure 7B, the title for the y axis should be "DNA released (%)".In Figure 7D, the title for the y axis should be "Survival (%)", and the scale for the y axis should be "100, 10 and 1". These corrections do not affect the conclusions of the study. We apologize for any inconvenience this may havecaused.展开更多
基金Acknowledgment This research was supported by grants from the Ministry of Science and Technology of China （2006CB943901, 2007CB948003） the National Natural Science Foundation of China （30600306, 30623003） Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences （2007KIP 101,2007KIP401）, Chinese Academy of Sciences.
文摘Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.
基金Acknowledgments We thank Drs Hua Gu （Columbia University, USA）, Weiguo Zhang （Duke University Medical Center, USA）, and Youhai H Chen （University of Pennsylvania, USA） for reviewing the manuscript and for suggestions, and Dr Ilia Voskoboinik （Peter MacCallum Cancer Centre, Australia） for providing the mouse perforin cDNA in pKS（＋） Bluescript. Ragl^-/- mice were gifts from Xiaolong Liu （Shanghai Institutes for Biological Sciences, China）. This work was supported by grants from the National Natural Science Foundation of China （30325018, 30530700, 30623003, and 30421005） and CAS project （KSCX1-YW-R-43）, grants from the National Key Project 973 （2006CB504300 and 2007CB512404）, grants from the Technology Commission of Shanghai Municipality （04DZ14902, 04DZ19108, 06DZ22032, 04DZ19112, 07XD14033, and 07DZ22916）, 863 key project （2006AA02A247）, and a grant from the E-institutes of Shanghai Universities Immunology Division.
文摘Perforin 是主要从事调停的形成毛孔的蛋白质目标 T 房间死亡并且被细胞毒素的 T 淋巴细胞(CTL ) 和自然漂亮房间采用。然而，它是否也在常规 CD4+ T 房间功能起一个作用，仍然保持不清楚。这里，我们报导那在 perforin 缺乏(PKO ) 老鼠， CD4+ T 房间是响应 T 的 hyperproliferative 房间受体(TCR ) 刺激。hyperproliferation 的这个特征被改进在房间分割并且在 IL-2 分泌物伴随。看起来， perforin 缺乏不在胸腺怒气和淋巴节点影响 T 房间开发。在 vivo， perforin 缺乏导致增加的抗原特定的 T 房间增长和抗体生产。而且， PKO 老鼠更产生试验性的自体免疫的眼色素层炎。探讨分子的机制，我们发现在 TCR 刺激以后，从 PKO 老鼠的 CD4+ T 房间显示增加的细胞内部的钙流动并且随后提高抄写因素 NFAT1 的激活。我们的结果显示 perforin 在由影响 TCR 依赖的 Ca2+ 发信号调整 CD4+ T 房间激活和有免疫力的反应起一个否定作用。
基金We thank Drs J Zhao, DS Li, L Xiao （Chinese Academy of Sciences, China）, Drs B Leo and H Wang （Agilent Technologies, USA） for helpful discussions and technical assistance, and Drs HK Mei and Y Qiu （GlaxoSmithKline, UK） for the DAVID analysis. This research was supported by the Ministry of Science and Technology （2005CB522406, 2006CB943900, 2007CB947904, 2007CB947100, 2009CB941100, and 2007CB948000）, National Natural Science Foundation of China （30621091, 30625014, 30623003, and 90713047）, Shanghai Municipal Commission for Science and Technology （07PJ14099, 06ZR14098, and 06DZ22032）, and the Chinese Academy of Sciences （KSCX2-YW-R-56 and 2007KIP204）.
基金We thank Lanying Sun, Yang Xiao, Yuelei Chen, Hua Zhou and Cell Analysis Center （Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences） for professional technical assistance. This work was supported in part by grants from Hi-Tech Research Development Program of China （863 Program, No. 2007AA021006） the Key Project of the Chinese Academy of Sciences （No. KSCX2-YW- R-09）+1 种基金 the 973 Project （No. 2004CB518804） Grant 30623003 from National Nature Science Foundation of China and Grant 06DZ22032 from Science and Technology Commission of Shang- hai Municipality.
文摘Vascular endothelial cell growth inhibitor （VEGI） is a member of the tumor necrosis factor superfamily and plays an important role in vascular homeostasis. In this study, to investigate the anticancer therapeutic potential of this gene, a secreted isoform of VEGI （VEGI-251） was inserted into a selectively replicating adenovirus with E1B 55 kDa gene deletion （ZD55） to construct ZD55-VEGI-251. We report here that secreted VEGI-251 produced from ZD55- VEGI-251-infected cancer cells potently inhibits endothelial cell proliferation, tube formation in vitro and angiogen- esis of chick chorioallantoic membrane in vivo. Additionally, ZD55-VEGI-251 infection leads to a much more severe cytopathic effect than control viruses on several human cancer cell lines, including cervical cancer cell line HeLa, hepatoma cell line SMMC-7721 and colorectal cancer cell line SW620. Further study reveals that the increased cytotoxicity is a result of VEGI-251 autocrine-dependent, mitochondria-mediated apoptosis accompanied by caspase-9 activation, enhanced caspase-3 activation and PARP cleavage. Moreover, ZD55-VEGI-251-treatment of athymic nude mice bearing human cervical and colorectal tumor xenografts markedly suppressed tumor growth. Our findings indicate that the combined effect of antiangiogenesis and apoptosis-induction activity makes the VEGI-251-armed oncolytic adenovirus a promising therapeutic agent for cancer.
文摘The aim of this study was to determine the effects of antioxidants,including α-ketoacids （α-ketoglutarate and pyruvate）,lactate and glutamate/malate combination,against oxidative stress on rat spermatozoa. Our results showed that H2O2 （250 μmol L^-1）-induced damages,such as impaired motility,adenosine triphosphate （ATP） depletion,inhibition of sperm protein phosphorylation,reduced acrosome reaction and decreased viability,could be significantly prevented by incubation of the spermatozoa with α-ketoglutarate （4 mmol L^-1） or pyruvate （4 mmol L^-1）. Without exogenous H2O2 in the medium,the addition of pyruvate （4 mmol L^-1） significantly increased the superoxide anion （O2^-·） level in sperm suspension （P≤0.01）,whereas the addition of α-ketoglutarate （4 mmol L^-1） and lactate （4 mmol L^-1） significantly enhanced tyrosine-phosphorylated proteins with the size of 95 kDa （P≤0.04）. At the same time,α-ketoglutarate,pyruvate,lactate,glutamate and malate supplemented in media can be used as important energy sources and supply ATP for sperm motility. In conclusion,the present results show that α-ketoacids could be effective antioxidants for protecting rat spermatozoa from H2O2 attack and could be effective components to improve the antioxidant capacity ofBiggers,Whitten and Whittingham media.
基金This work was supported by grants from the Chinese Ministry of Science ＆ Technology （No. 2004AA221130）, the Shanghai Metropolitan Fund for Research and Development （No. 07DJ14005）, the National Natural Science Foundation of China （Nos. 30525041, 30721004）, and the State Key Program for Basic Research of China （No. 2006CB500704）.
基金National Natural Science Foundation of China(No.31071213,81101479,30971481,81260148,81271425 and 81160118)Clinical Medicine Research Special-purpose Foundation of China(No.L2012052)+3 种基金Natural Science Foundation of Jiangxi Province,China(No.20114BAB215029)Technology Foundation of Jiangxi Province,China(No 20111BBG70026-2)Health Department Science and Technology Foundation of Jiangxi Province,China(No.20121026)Education Department Youth Scientific Research Foundation of Jiangxi Province,China(No.GJJ12158)
文摘AIM:To investigate the acetylcholinesterase（AChE）expression involved in retina pigment epithelial（RPE）apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 was from ATCC（Rockville,MD）.Cultured ARPE-19 cells were treated with H2O2 at 0,250,500,1000,2 000μmol/L and cell viability was measured with MTT assay.AChE expression and DNA fragments were analyzed by immunocytochemistry,TUNEL and PARP-1Western blotting.RESULTS:Immunofluorescence detected AChE exist in the normal human retinal tissue.When H2O2】500μmol/L,AChE expression showed an increase after 2h,and this concentration was selected for the present study.RPE cell was induced with 1 000μmoI/L H2O2 for 2h,compared to the control group,cell activity decline detected by MTT,AChE and PARP-1 protein expression was significantly increased detected by Western blotting.AChE immunofluorescence staining was positive in RPE cell after HO2 incubate 2h.In addition,pretreatment with100|jmol/L epigallocatechin gallate（EGCG）,cell viability increased from 31.20%±3.90%to 70.23%±12.96%.CONCLUSION:AChE is weakly expressed in normal human RPE cells.Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells,which may indicate that AChE may be an important role in AMD.
基金This work was supported by the grants from National Natural Science Foundation of China(Nos.30170208,30623003 and 30170208)from the Ministry of Science and Technology,China(No.2001AA233031 and No.2001CB510205)from US NIH(CA50519)(to DJ Chen).
基金Acknowledgments We thank X Wu （Fudan University） for LckCre mouse and K Wong （Dana-Farber Cancer Institute） for LKB1 mouse, R Bosselut （National Institutes of Health） and D Li （Shanghai Institutes for Biological Sciences） for instructive comments on the manuscript We are grateful to our colleagues F Liu for animal husbandry, W Bian for cell sorting and X Wang for real-time PCR analysis. This research was supported in part by the National Natural Science Foundation of China （30872290, 30925031）, the Ministry of Science and Technology （2006CB504303, 2007CB815802, 2009ZX 10004-105）, the Hi-Tech Research and Development Program of China （2007AA02Z167）, the National Basic Research Program of China （2007CB914504） and the Chinese Academy of Sciences （KSCX 1-YW-R-43, KSCX2-YW-R-10）.
基金Acknowledgments We thank ProfYongjun Liu, Dangsheng Li and Yangxin Fu for helpful comments and Dr Sheri Skinner for reviewing the manuscript and for constructive suggestions. This work was supported by grants from the National Natural Science Foundation of China （30530700, 30623003, 30600568, 30721065, 90713044, 30600308, 30801011, 30870126） and CAS project （KSCX1-YW-R-43）, grant from SIBS project （2007KIP301）, grants from the Ministry of Science and Technology （2006CB504300, 2007CB512404, 2006AA02A247, 20072714）, the Technology Commission of Shanghai Municipality （88014199, 07DZ22916, 07XD14033, 064319034, 08431903004, 2008ZX10206, 08DZ2291703）, EU project （FP6-2005-SSP-5-B, SP5B-CT-2006-044161） and from the E-institutes of Shanghai Universities Immunology Division.
基金We thank Dr Bin Zhang （University of Michigan, USA） for providing the MCFD2 antibodies. This work was supported in part by the Life Science Special Fund of the Chinese Academy of Sciences for Human Genome Research （KJ95T-06 and KSCX1-Y02 to BML, NHJ and MLJ）, the National Natural Science Foundation of China （30225023 and 30430240 to BML and 90208011, 30300174, 30470856, 30421005 and 30623003 to NHJ）, the National Key Basic Research and Development Program of China （2006CB500807 to BML and 2002CB713802, 2005CB522704 and 2006CB943902 to NHJ）, the National High-Tech Research and Development Program of China （2006AA02ZI99 to BML and 2006AA02Z186 to NHJ）, the Shanghai Key Project of Basic Science Research （04DZ14005 to BML and 04DZ14005, 04DZ05608, 06DJI4001 and 06DZ22032 to NHJ）, the Council of the Shanghai Municipal for Science and Technology （05814578 to NHJ）, and the US National Institutes of Health （DA013471 and DA020555 to LY）.
基金supported by the grants from National Natural Science Foundation of China(No.30170208,30623003 and 30270335)from the Ministry of Science and Technology,China(No.2001AA233031 and No.2001CB510205)+1 种基金from the Shanghai Municipal Council for Science and Technology(No.06DZ22032)from US NIH(CA50519)(to DJ Chen).
文摘The author affiliations were mixed up in the previous published version. The third fund number of National NaturalScience Foundation of China in the Acknowledgments was wrong, it should be "30270335". The Shanghai MunicipalCouncil for Science and Technology (No.06DZ22032) was missed in the Acknowledgments. There are some labelingand production errors in Figure 2A, Figure 3B and 3C, Figure 5C, Figure 6B and 6E, Figure 7B and 7D. In Figure 2A,left panel "A431" should be "Par3". In Figure 3B and 3C, "anti-Par3CT" should be "anti-Par3LCT", "GST-Par3CT"should be "GST-Par3LCT". In Figure 5C, the second arrow indicating "Lamin B" should be "[3-tubulin". In Figure 6Bright panel, the molecular weight for ?-actin should be "43" instead of"200". In Figure 6E, "Par3" should be "Par3i". Themolecular weight for the DNA-PKcs panel should be the same as the p-DNA-PKcs. In Figure 7B, the time point "240"in the left panel should be "120"; in the right panel of Figure 7B, the title for the y axis should be "DNA released (%)".In Figure 7D, the title for the y axis should be "Survival (%)", and the scale for the y axis should be "100, 10 and 1". These corrections do not affect the conclusions of the study. We apologize for any inconvenience this may havecaused.
