目的:采用Meta分析评价TERT启动子突变和膀胱癌临床病理特征的关系。方法:检索Cochrane Library、Embase、PubMed、Web of Science、万方全文数据库、中国知网数据库,搜索与TERT启动子突变相关的膀胱癌的病例对照研究,检索截至2024年11...目的:采用Meta分析评价TERT启动子突变和膀胱癌临床病理特征的关系。方法:检索Cochrane Library、Embase、PubMed、Web of Science、万方全文数据库、中国知网数据库,搜索与TERT启动子突变相关的膀胱癌的病例对照研究,检索截至2024年11月。两名研究人员独立筛选文献、提取信息、整理数据、评估纳入研究的偏倚风险,然后使用Review Manager 5.3进行汇总分析。结果:经数据库检索后,共检索到1575篇文献,排除综述论文、会议论文和无关研究等文献后,最终共纳入8篇文献,共1130例患者。Meta分析结果表明,TERT启动子突变与性别之间存在关联,男性患者比女性患者更易发生TERT启动子突变。结论:与女性膀胱癌患者相比,男性膀胱癌患者更容易出现TERT启动突变,这暗示了膀胱癌中存在与性别相关的潜在分子机制,为实验室和临床肿瘤研究提供了新的方向。Objective: To evaluate the relationship between TERT promoter mutations and clinical pathological features of bladder cancer using a Meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases for case-control studies on TERT promoter mutations in bladder cancer, with data up to November 2024. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was conducted using Review Manager 5.3. Results: A total of 1575 studies were identified through database searches. After excluding review articles, conference papers, and irrelevant studies, 8 studies with a total of 1130 patients were included. The Meta-analysis results showed that TERT promoter mutations are somewhat related to gender, with males being more likely to have TERT promoter mutations than females. Conclusion: Male bladder cancer patients are more likely to experience TERT promoter mutations compared to female bladder cancer patients. This suggests the presence of gender-related potential molecular mechanisms in bladder cancer, providing new insights for laboratory and clinical cancer research.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,su...BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.展开更多
Aim： To characterize the coexpression of survivin, an inhibitor of apoptosis （IAF）, and human telomerase reverse transcriptase （hTERT） in human testes with varying spermatogenic function. Methods： Transcript lev...Aim： To characterize the coexpression of survivin, an inhibitor of apoptosis （IAF）, and human telomerase reverse transcriptase （hTERT） in human testes with varying spermatogenic function. Methods： Transcript levels of survivin mRNA and hTERT mRNA were determined in normal testes （n = 11） and testes with defective spermatogenesis （n = 28） using real-time reverse-transcription polymerase chain reaction （RT-PCR）. The histological work-up was performed according to a modified Johnsen score. Results： Expressions of both survivin and hTERT were highest at median levels of 96.8 and 709 in normal spermatogenesis and dropped to 53.3 and 534 in testes with postmeiotic spermatogenic arrest （n = 10）. In severe spermatogenic failure （n = 18）, survivin expression was lacking in most specimens （n = 16）, whereas at least low levels of testicular hTERT expression were largely detectable with a normalized expression of 73 in premeiotic spermatogenic arrest （n = 7） and 45 in patients with Sertoli cell-only syndrome （SCOS） （n = 3）. Both survivin and hTERT expressions increased with a progressing Johnsen score （P for trend = 0.001）. Conclusion： Although both survivin and hTERT are correlated with spermatogenic function, they show different expression patterns in testes of infertile patients. These findings substantiate results from studies in the rodent testis suggesting a predominant expression of survivin in meiotically dividing germ cells. （Asian J Andro12006 Jan; 8： 95-100）展开更多
Aim:To evaluate the quantitative detection of human telomerase RNA(hTR)and human telomerase reverse tran-scriptase(hTERT)mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients present...Aim:To evaluate the quantitative detection of human telomerase RNA(hTR)and human telomerase reverse tran-scriptase(hTERT)mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients presentingwith non-obstructive azoospermia.Methods:hTR and hTERT mRNA expression were quantified in 38 cryopre-served testicular tissue specimens by fluorescence real-time reverse transcription-polymerase chain reaction(RT-PCR)in a LightCycler(r).This was paralleled by conventional histological workup in all tissue specimens and additionalsemithin sectioning preparation in cases with maturation arrest(n=12)and Sertoli-cell-only syndrome(n=12).Re-sults;The average normalized hTERT expression(N_(hTERT))was 131.9±48.0 copies(mean±SD)in tissue speci-mens with full spermatogenesis,N_(hTERT)=51.2±17.2 copies in those with maturation arrest and N_(hTERT)=2.7±2.4copies in those with Sertoli-cell-only syndrome(SCOS).The discriminant analysis showed that detection of N_(hTERT)(N_(hTR))had a predictive value of 86.8%(55.3%)for correct classification in one of the three histological subgroups.Conclusion;Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue en-ables a molecular-diagnostic classification of gametogenesis.Quantitative detection of hTERT in testicular biopsies isthus well suited for supplementing the histopathological evaluation.展开更多
文摘目的:采用Meta分析评价TERT启动子突变和膀胱癌临床病理特征的关系。方法:检索Cochrane Library、Embase、PubMed、Web of Science、万方全文数据库、中国知网数据库,搜索与TERT启动子突变相关的膀胱癌的病例对照研究,检索截至2024年11月。两名研究人员独立筛选文献、提取信息、整理数据、评估纳入研究的偏倚风险,然后使用Review Manager 5.3进行汇总分析。结果:经数据库检索后,共检索到1575篇文献,排除综述论文、会议论文和无关研究等文献后,最终共纳入8篇文献,共1130例患者。Meta分析结果表明,TERT启动子突变与性别之间存在关联,男性患者比女性患者更易发生TERT启动子突变。结论:与女性膀胱癌患者相比,男性膀胱癌患者更容易出现TERT启动突变,这暗示了膀胱癌中存在与性别相关的潜在分子机制,为实验室和临床肿瘤研究提供了新的方向。Objective: To evaluate the relationship between TERT promoter mutations and clinical pathological features of bladder cancer using a Meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases for case-control studies on TERT promoter mutations in bladder cancer, with data up to November 2024. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was conducted using Review Manager 5.3. Results: A total of 1575 studies were identified through database searches. After excluding review articles, conference papers, and irrelevant studies, 8 studies with a total of 1130 patients were included. The Meta-analysis results showed that TERT promoter mutations are somewhat related to gender, with males being more likely to have TERT promoter mutations than females. Conclusion: Male bladder cancer patients are more likely to experience TERT promoter mutations compared to female bladder cancer patients. This suggests the presence of gender-related potential molecular mechanisms in bladder cancer, providing new insights for laboratory and clinical cancer research.
基金Supported by National Natural Science Foundation of China,No.82000792General Project of Chongqing Natural Science Foundation,No.CSTB2023NSCQ-MSX0246 and No.CSTB2022NSCQ-MSX1271+1 种基金Research Project of the State Administration of Traditional Chinese Medicine on Collaborative Chronic Disease Management of Traditional Chinese Medicine and Western Medicine,No.CXZH2024087Science and Health Joint Project of Dazu District Science and Technology Bureau,No.DZKJ2024JSYJ-KWXM1002.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.
文摘目的检测子痫前期孕妇血清中人端粒酶反转录酶(human telomerase reverse transcriptase,hTERT)、沉默信息调节因子6(silent information regulator 6,Sirt6)表达,并探究hTERT,Sirt6水平表达与疾病严重程度及妊娠结局评估中的价值。方法选取2018年1月~2022年12月在陕西省人民医院进行诊治的300例子痫前期孕妇作为子痫前期组,孕妇均符合《妊娠期高血压疾病诊治指南(2015)》中子痫前期诊断标准,选取同时期孕检的300例健康孕妇为对照组,根据病情严重程度将子痫前期组分为轻症子痫前期组(n=180)和重症子痫前期组(n=120),根据是否发生不良妊娠结局将子痫前期组分为正常妊娠组(n=165)和不良妊娠组(n=135)。酶联免疫吸附实验(enzyme-linked immunosorbnent assay,ELISA)法检测血清中hTERT和Sirt6水平,Spearman相关性分析血清中hTERT和Sirt6水平与子痫前期孕妇病情严重程度的相关性,利用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清hTERT和Sirt6水平在子痫前期诊断及妊娠结局预测中的价值。结果与对照组比较,子痫前期组血清hTERT(22.15±5.82 ng/ml vs 30.12±9.56 ng/ml),Sirt6(5.26±1.62 ng/ml vs 7.06±2.29 ng/ml)水平降低,差异具有统计学意义(t=12.334,11.114,均P<0.001)。与轻症子痫前期组比较,重症子痫前期组孕妇血清hTERT(18.28±4.11 ng/ml vs 24.73±6.96 ng/ml),Sirt6(4.03±1.17 ng/ml vs 6.08±1.92 ng/ml)水平降低,差异具有统计学意义(t=9.142,10.469,均P<0.001)。与正常妊娠组比较,不良妊娠组子痫前期孕妇血清中hTERT(17.75±4.61 ng/ml vs 25.75±6.81 ng/ml),Sirt6(4.06±0.96 ng/ml vs 6.24±2.16 ng/ml)水平降低,差异具有统计学意义(t=11.639,10.878,均P<0.001)。Spearman相关性分析显示,血清hTERT,Sirt6水平与子痫前期孕妇疾病严重程度均呈负相关(r=-0.562,-0.604,均P<0.001)。ROC曲线分析结果显示,血清hTERT,Sirt6诊断子痫前期的曲线下面积(95%置信区间)[AUC(95%CI)]分别为0.711(0.673~0.747),0.727(0.689~0.762),两者联合诊断子痫前期的AUC(95%CI)为0.788(0.753~0.820),高于两者单独诊断(Z=2.719,2.154,P=0.007,0.031);血清hTERT,Sirt6预测子痫前期不良妊娠结局的AUC(95%CI)分别为0.786(0.735~0.831),0.783(0.732~0.829),两者联合预测子痫前期不良妊娠结局的AUC(95%CI)为0.849(0.804~0.888),高于两者单独预测(Z=1.855,1.861,P=0.032,0.031)。结论hTERT和Sirt6在子痫前期孕妇血清中水平较低,与子痫前期孕妇疾病严重程度均呈负相关,并对妊娠结局具有一定的评估价值。
文摘Aim： To characterize the coexpression of survivin, an inhibitor of apoptosis （IAF）, and human telomerase reverse transcriptase （hTERT） in human testes with varying spermatogenic function. Methods： Transcript levels of survivin mRNA and hTERT mRNA were determined in normal testes （n = 11） and testes with defective spermatogenesis （n = 28） using real-time reverse-transcription polymerase chain reaction （RT-PCR）. The histological work-up was performed according to a modified Johnsen score. Results： Expressions of both survivin and hTERT were highest at median levels of 96.8 and 709 in normal spermatogenesis and dropped to 53.3 and 534 in testes with postmeiotic spermatogenic arrest （n = 10）. In severe spermatogenic failure （n = 18）, survivin expression was lacking in most specimens （n = 16）, whereas at least low levels of testicular hTERT expression were largely detectable with a normalized expression of 73 in premeiotic spermatogenic arrest （n = 7） and 45 in patients with Sertoli cell-only syndrome （SCOS） （n = 3）. Both survivin and hTERT expressions increased with a progressing Johnsen score （P for trend = 0.001）. Conclusion： Although both survivin and hTERT are correlated with spermatogenic function, they show different expression patterns in testes of infertile patients. These findings substantiate results from studies in the rodent testis suggesting a predominant expression of survivin in meiotically dividing germ cells. （Asian J Andro12006 Jan; 8： 95-100）
文摘Aim:To evaluate the quantitative detection of human telomerase RNA(hTR)and human telomerase reverse tran-scriptase(hTERT)mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients presentingwith non-obstructive azoospermia.Methods:hTR and hTERT mRNA expression were quantified in 38 cryopre-served testicular tissue specimens by fluorescence real-time reverse transcription-polymerase chain reaction(RT-PCR)in a LightCycler(r).This was paralleled by conventional histological workup in all tissue specimens and additionalsemithin sectioning preparation in cases with maturation arrest(n=12)and Sertoli-cell-only syndrome(n=12).Re-sults;The average normalized hTERT expression(N_(hTERT))was 131.9±48.0 copies(mean±SD)in tissue speci-mens with full spermatogenesis,N_(hTERT)=51.2±17.2 copies in those with maturation arrest and N_(hTERT)=2.7±2.4copies in those with Sertoli-cell-only syndrome(SCOS).The discriminant analysis showed that detection of N_(hTERT)(N_(hTR))had a predictive value of 86.8%(55.3%)for correct classification in one of the three histological subgroups.Conclusion;Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue en-ables a molecular-diagnostic classification of gametogenesis.Quantitative detection of hTERT in testicular biopsies isthus well suited for supplementing the histopathological evaluation.
