BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
中国科学院深圳先进技术研究院计算机辅助药物设计中心袁曙光研究员团队参与的研究在嗅觉受体蛋白Olfr73分子活性机制取得进展。相应成果为“Yuan SG,Dahoun T,Brugarolas M,et al.Computational modeling of the olfactory receptor Ol...中国科学院深圳先进技术研究院计算机辅助药物设计中心袁曙光研究员团队参与的研究在嗅觉受体蛋白Olfr73分子活性机制取得进展。相应成果为“Yuan SG,Dahoun T,Brugarolas M,et al.Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compounds[J].Communication Biology,2019,2:141(通过嗅觉受体蛋白Olfr73的计算机模拟阐明低活性嗅觉受体激活化合物的分子作用机制)”。展开更多
[目的]分析1992—2021年中国40~74岁结直肠癌筛查人群的疾病负担变化趋势,为优化结直肠癌筛查策略和降低疾病负担提供科学依据。[方法]基于2021年全球疾病负担(Global Burden of Disease,GBD)数据,选取1992—2021年中国40~74岁结直肠癌...[目的]分析1992—2021年中国40~74岁结直肠癌筛查人群的疾病负担变化趋势,为优化结直肠癌筛查策略和降低疾病负担提供科学依据。[方法]基于2021年全球疾病负担(Global Burden of Disease,GBD)数据,选取1992—2021年中国40~74岁结直肠癌的发病、死亡、伤残调整寿命年(disability-adjusted life years,DALY)等数据,采用Joinpoint和年龄-时期-队列模型分析发病和死亡趋势并计算平均年度变化百分比(average annual percentage change,AAPC)及其95%置信区间(confidence interval,CI),并进行分解分析。[结果] 1992—2021年,筛查人群结直肠癌发病、死亡和DALY数量均呈上升趋势,男性上升幅度超过女性。发病粗率和男性死亡、DALY粗率均呈上升趋势,而女性死亡和DALY粗率均呈下降趋势。发病标化率男性(AAPC=2.25%,95%CI:2.17%~2.32%)增长高于女性(AAPC=1.03%,95%CI:0.97%~1.07%);男女性死亡和DALY标化率均呈现下降趋势,男性(AAPC=-0.13%,95%CI:-0.18%~-0.09%)下降低于女性(AAPC=-1.41%,95%CI:-1.47%~-1.36%),男性(AAPC=-0.10%,95%CI:-0.14%~-0.06%)DALY标化率下降幅度也低于女性(AAPC=-1.47%,95%CI:-1.52%~-1.43%)。年龄-时期-队列分析显示,结直肠癌风险随年龄增长呈上升趋势,男性各年龄组发病和死亡风险均显著高于女性。2007年后男女性发病风险均持续升高,而女性死亡和DALY风险持续下降。男性发病风险从1920—1924年的0.50(95%CI:0.46~0.54)增加到1975—1979年2.25(95%CI:2.03~2.49)。分解分析表明,人口增长和老龄化是发病率增长的主要原因,流行病学变化对发病率呈正向贡献,占37.27%,而对死亡率和DALY率呈负向贡献,分别占-30.13%和-31.63%。[结论]我国结直肠癌筛查人群结直肠癌疾病负担呈现“发病数、死亡数及DALY数、发病率持续攀升而标化死亡率、DALY显著下降”的双重特征,且存在明显的性别、年龄和出生队列差异。展开更多
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.
文摘中国科学院深圳先进技术研究院计算机辅助药物设计中心袁曙光研究员团队参与的研究在嗅觉受体蛋白Olfr73分子活性机制取得进展。相应成果为“Yuan SG,Dahoun T,Brugarolas M,et al.Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compounds[J].Communication Biology,2019,2:141(通过嗅觉受体蛋白Olfr73的计算机模拟阐明低活性嗅觉受体激活化合物的分子作用机制)”。
