Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk....Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.展开更多
背景与目的骨代谢标志物是一类源于骨基质或骨细胞的代谢指标,可反映骨代谢情况。本研究旨在探讨血清骨代谢生化指标I型胶原交联羧基端肽(cross-linked telopeptide of type I collage,ICTP)和骨特异性碱性磷酸酶(bone-specific alkalin...背景与目的骨代谢标志物是一类源于骨基质或骨细胞的代谢指标,可反映骨代谢情况。本研究旨在探讨血清骨代谢生化指标I型胶原交联羧基端肽(cross-linked telopeptide of type I collage,ICTP)和骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BAP)在肺癌骨转移诊断中的意义及其临床应用价值。方法采用前瞻性对照方法,共入组110例,分为3组。初治肺癌患者共90例,临床分期为IV期,分为骨转移组50例和非骨转移组40例,健康对照组20例,采用酶联免疫法和电化学发光免疫测定法检测所有入组者治疗前的血清骨代谢生化指标ICTP和BAP水平,对骨转移的各因素与血清ICTP和BAP的相关性进行统计学分析。结果骨转移组的血清ICTP和BAP水平显著高于非骨转移组和健康对照组(P<0.05)。多发性骨转移组(骨转移数≥3)的血清BAP水平显著高于少发性骨转移组(骨转移数<3)(P<0.05)。混合性骨转移组的血清BAP水平显著高于溶骨性骨转移组(P<0.05)。ICTP和BAP在肺癌骨转移诊断中的敏感性分别为18%和40%,特异性分别为98.3%和95%,准确度分别为61.8%和70%。联合检测血清ICTP和BAP可提高其敏感性和准确度(分别为52%和74.5%)。结论由于检测方便、无创性、成本较低,血清骨代谢生化指标ICTP和BAP在肺癌骨转移的临床诊断中有一定的实用价值。展开更多
背景与目的肺癌易发生骨转移,I型胶原羧基端肽β特殊序列(β isomer of C-terminal telopeptide of type I collagen,β-CTX)和骨源性碱性磷酸酶(bone-specific alkaline phosphates,BAP)在骨质代谢中是重要的生化标记物,本研究旨在探...背景与目的肺癌易发生骨转移,I型胶原羧基端肽β特殊序列(β isomer of C-terminal telopeptide of type I collagen,β-CTX)和骨源性碱性磷酸酶(bone-specific alkaline phosphates,BAP)在骨质代谢中是重要的生化标记物,本研究旨在探讨骨代谢生化指标和肺癌骨转移进展程度的相关性,有助于早期判断是否有肺癌骨转移的发生。方法天津市人民医院2009年7月-2012年7月共收治92例肺癌并发生骨转移患者,全部病例其原发灶均经细胞学检查证实,骨转移灶的数目及类型经ECT结合X线片、CT证实,采用ELISA方法检测血β-CTX、BAP的浓度水平。结果收集的92例肺癌伴骨转移的患者中,转移灶<3处为58例,≥3处为34例;溶骨型68例,成骨型9例,混合型15例。血β-CTX、BAP水平在不同的骨转移数目组间差异有统计学意义(P<0.05),β-CTX在肺癌溶骨型骨转移患者中具有较高的敏感性。结论骨代谢生化指标β-CTX、BAP对肺癌骨转移具有辅助诊断意义,是判断转移进展程度的良好指标。展开更多
为了解膜下滴灌土壤硝化、反硝化作用的变化规律,应用气压过程分离(Barometric process separation,BaPS)方法,研究了施氮肥、有机肥与氮肥配施和不施肥3种不同施肥处理的土壤硝化、反硝化速率在覆膜与裸地条件下的动态变化。结果显示,...为了解膜下滴灌土壤硝化、反硝化作用的变化规律,应用气压过程分离(Barometric process separation,BaPS)方法,研究了施氮肥、有机肥与氮肥配施和不施肥3种不同施肥处理的土壤硝化、反硝化速率在覆膜与裸地条件下的动态变化。结果显示,不同处理下土壤硝化、反硝化作用随着玉米生育期的推移有明显的变化。相同栽培措施不同施肥处理间土壤硝化、反硝化速率差异均达极显著水平,且大小顺序为氮+有机肥配施处理>施氮肥处理>不施肥处理(对照);相同施肥处理不同栽培措施间土壤硝化、反硝化速率大小顺序均为覆膜处理>裸地处理。展开更多
文摘Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.
文摘背景与目的骨代谢标志物是一类源于骨基质或骨细胞的代谢指标,可反映骨代谢情况。本研究旨在探讨血清骨代谢生化指标I型胶原交联羧基端肽(cross-linked telopeptide of type I collage,ICTP)和骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BAP)在肺癌骨转移诊断中的意义及其临床应用价值。方法采用前瞻性对照方法,共入组110例,分为3组。初治肺癌患者共90例,临床分期为IV期,分为骨转移组50例和非骨转移组40例,健康对照组20例,采用酶联免疫法和电化学发光免疫测定法检测所有入组者治疗前的血清骨代谢生化指标ICTP和BAP水平,对骨转移的各因素与血清ICTP和BAP的相关性进行统计学分析。结果骨转移组的血清ICTP和BAP水平显著高于非骨转移组和健康对照组(P<0.05)。多发性骨转移组(骨转移数≥3)的血清BAP水平显著高于少发性骨转移组(骨转移数<3)(P<0.05)。混合性骨转移组的血清BAP水平显著高于溶骨性骨转移组(P<0.05)。ICTP和BAP在肺癌骨转移诊断中的敏感性分别为18%和40%,特异性分别为98.3%和95%,准确度分别为61.8%和70%。联合检测血清ICTP和BAP可提高其敏感性和准确度(分别为52%和74.5%)。结论由于检测方便、无创性、成本较低,血清骨代谢生化指标ICTP和BAP在肺癌骨转移的临床诊断中有一定的实用价值。
文摘背景与目的肺癌易发生骨转移,I型胶原羧基端肽β特殊序列(β isomer of C-terminal telopeptide of type I collagen,β-CTX)和骨源性碱性磷酸酶(bone-specific alkaline phosphates,BAP)在骨质代谢中是重要的生化标记物,本研究旨在探讨骨代谢生化指标和肺癌骨转移进展程度的相关性,有助于早期判断是否有肺癌骨转移的发生。方法天津市人民医院2009年7月-2012年7月共收治92例肺癌并发生骨转移患者,全部病例其原发灶均经细胞学检查证实,骨转移灶的数目及类型经ECT结合X线片、CT证实,采用ELISA方法检测血β-CTX、BAP的浓度水平。结果收集的92例肺癌伴骨转移的患者中,转移灶<3处为58例,≥3处为34例;溶骨型68例,成骨型9例,混合型15例。血β-CTX、BAP水平在不同的骨转移数目组间差异有统计学意义(P<0.05),β-CTX在肺癌溶骨型骨转移患者中具有较高的敏感性。结论骨代谢生化指标β-CTX、BAP对肺癌骨转移具有辅助诊断意义,是判断转移进展程度的良好指标。
文摘为了解膜下滴灌土壤硝化、反硝化作用的变化规律,应用气压过程分离(Barometric process separation,BaPS)方法,研究了施氮肥、有机肥与氮肥配施和不施肥3种不同施肥处理的土壤硝化、反硝化速率在覆膜与裸地条件下的动态变化。结果显示,不同处理下土壤硝化、反硝化作用随着玉米生育期的推移有明显的变化。相同栽培措施不同施肥处理间土壤硝化、反硝化速率差异均达极显著水平,且大小顺序为氮+有机肥配施处理>施氮肥处理>不施肥处理(对照);相同施肥处理不同栽培措施间土壤硝化、反硝化速率大小顺序均为覆膜处理>裸地处理。