目的:探讨miR-2355-3p对口腔鳞状细胞癌放射敏感性的影响及其机制。方法:回顾性收集20例口腔鳞状细胞癌和20例正常口腔黏膜组织,qRT-PCR法检测miR-2355-3p的表达,分析miR-2355-3p表达与患者临床病理特征的关系。利用TCGA数据分析miR-235...目的:探讨miR-2355-3p对口腔鳞状细胞癌放射敏感性的影响及其机制。方法:回顾性收集20例口腔鳞状细胞癌和20例正常口腔黏膜组织,qRT-PCR法检测miR-2355-3p的表达,分析miR-2355-3p表达与患者临床病理特征的关系。利用TCGA数据分析miR-2355-3p在口腔鳞状细胞癌中的表达、预后及诊断价值。qRT-PCR检测细胞中miR-2355-3p、丝氨酸蛋白酶抑制剂家族A成员3(serpin family A member 3,SERPINA3)的相对表达情况,CCK-8、EdU和流式细胞术检测细胞活力、增殖和凋亡。TargetScan 8.0预测miR-2355-3p潜在的下游靶基因及结合位点。双荧光素酶报告基因实验验证miR-2355-3p与SERPINA3的相关性。qRT-PCR和Western blot检测FADU细胞中SERPINA3 mRNA和蛋白的表达。结果:miR-2355-3p在口腔麟状细胞癌中高表达。高水平miR-2355-3p的口腔鳞状细胞癌患者预后较差。miR-2355-3p预测口腔鳞癌的AUC为0.864(95%CI:0.798~0.931)。miR-2355-3p inhibitor下调miR-2355-3p表达。电离辐射(ionizing radiation, IR)处理抑制FADU细胞活性和增殖,促进细胞凋亡。转染miR-2355-3p inhibitor后,miR-2355-3p inhibitor进一步抑制FADU细胞活性和增殖,促进细胞凋亡。miR-2355-3p可直接靶向SERPINA3。miR-2355-3p inhibitor促进FADU细胞SERPINA3 mRNA和蛋白的表达。结论:miR-2355-3p通过靶向SERPINA3增强口腔鳞状细胞癌细胞的放射敏感性。展开更多
目的:丝氨酸蛋白酶抑制剂A3(SerpinA3)在急性肾损伤(AKI)中的诊断及其预后价值。方法:前瞻性纳入广东省人民医院重症监护病房(ICU)收治的AKI患者(AKI组)93例和同期ICU非AKI患者(对照组)89例,用ELISA法检测患者的血液和尿液SerpinA3。收...目的:丝氨酸蛋白酶抑制剂A3(SerpinA3)在急性肾损伤(AKI)中的诊断及其预后价值。方法:前瞻性纳入广东省人民医院重症监护病房(ICU)收治的AKI患者(AKI组)93例和同期ICU非AKI患者(对照组)89例,用ELISA法检测患者的血液和尿液SerpinA3。收集患者临床资料及实验室检测数据。采用Spearman法分析血SerpinA3、尿SerpinA3与临床指标的相关性。对AKI患者随访28 d,用受试者工作曲线(ROC)和生存曲线对患者28 d存活及死亡进行分析。结果:AKI患者血SerpinA3[158250(107025,259575)ng/mL vs 125850(80775,196575)ng/mL,P<0.05]和尿SerpinA3[1618(678.8,5496)ng/mL vs 345.0(173.8,675.0)ng/mL,P<0.05]均较非AKI组显著增高。Spearman分析显示,尿SerpinA3与血清肌酐呈正相关(r=0.213,P<0.05)。尿SerpinA3在预测AKI患者的28 dd内病死率ROC曲线下面积为0.8,敏感度和特异度分别为72.73%和77.24%。Kaplan-Meier生存曲线分析结果显示,发生AKI时尿SerpinA3>5496 ng/mL的患者,28 d内生存率显著降低,预后较差。结论:SerpinA3对AKI诊断和预测患者预后有一定的价值,可作为AKI患者诊断和预后判断的生物学标志物。展开更多
Dysregulation of the Wnt pathway has been extensively studied in multiple diseases,including some angiogenic disorders.Wnt signaling activation is a major stimulator in pathological angiogenesis and thus,Wnt antagonis...Dysregulation of the Wnt pathway has been extensively studied in multiple diseases,including some angiogenic disorders.Wnt signaling activation is a major stimulator in pathological angiogenesis and thus,Wnt antagonists are believed to have therapeutic potential for neovascular disorders.Actually,some Wnt antagonists have been identified directly from the anti-angiogenic factor family.This review summarizes the recent progress toward understanding of the roles of Wnt pathway antagonists in angiogenic regulation and their mechanism of action,and exploring their therapeutic potential.展开更多
本研究旨在克隆西农萨能奶山羊SERPINA1基因的CDS区,采用生物软件和在线预测工具进行生物信息学分析,通过实时荧光定量PCR技术检测SERPINA1基因在西农萨能奶山羊各组织间mRNA的表达水平。根据GenBank中山羊SERPINA1基因CDS区序列(登录号...本研究旨在克隆西农萨能奶山羊SERPINA1基因的CDS区,采用生物软件和在线预测工具进行生物信息学分析,通过实时荧光定量PCR技术检测SERPINA1基因在西农萨能奶山羊各组织间mRNA的表达水平。根据GenBank中山羊SERPINA1基因CDS区序列(登录号:XM_018066209.1),利用Primer Premier 5.0软件设计特异性引物,RT-PCR扩增目的基因,构建原核表达载体测序后对序列进行生物信息学分析;采集西农萨能奶山羊心脏、肝脏、脾脏、肺脏、乳腺、肾脏、肌肉、瘤胃和小肠组织,提取组织RNA,反转录为cDNA模板,设计特异性定量引物,进行实时荧光定量PCR,检测SERPINA1基因在不同组织中的表达差异。结果显示,西农萨能奶山羊SERPINA1基因CDS区全长1326 bp,编码441个氨基酸;同源性比对分析显示,西农萨能奶山羊与山羊、绵羊、牛和小鼠SERPINA1基因核苷酸序列同源性分别为100%、98.6%、95.7%和71.6%,与山羊亲缘关系最近,其次是绵羊。SERPINA1蛋白分子质量为48.71 ku,等电点为5.71,为跨膜亲水蛋白;SERPINA1氨基酸序列分别有62个磷酸化位点,3个跨膜区结构。组织表达分析显示,SERPINA1基因在西农萨能奶山羊肝脏组织中显著高表达(P<0.05),其次是乳腺组织,在肺脏组织中表达量最低。研究结果为进一步探究SERPINA1基因在奶山羊乳蛋白合成代谢中的作用提供理论依据。展开更多
AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mea...AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene(mutation): ATP7B(H1069Q), HFE(C282Y, H63D),UGT1A1(TA)7, and SERPINA1(PiZ)] were detected by polymerase chain reaction(PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61(76%), 7(9%), and 12(15%) patients, respectively. Among all 86 patients, 50(58%) reached an early viral response and 70(81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls(patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The(TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels(beta regression coefficient =-295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.展开更多
文摘目的:探讨miR-2355-3p对口腔鳞状细胞癌放射敏感性的影响及其机制。方法:回顾性收集20例口腔鳞状细胞癌和20例正常口腔黏膜组织,qRT-PCR法检测miR-2355-3p的表达,分析miR-2355-3p表达与患者临床病理特征的关系。利用TCGA数据分析miR-2355-3p在口腔鳞状细胞癌中的表达、预后及诊断价值。qRT-PCR检测细胞中miR-2355-3p、丝氨酸蛋白酶抑制剂家族A成员3(serpin family A member 3,SERPINA3)的相对表达情况,CCK-8、EdU和流式细胞术检测细胞活力、增殖和凋亡。TargetScan 8.0预测miR-2355-3p潜在的下游靶基因及结合位点。双荧光素酶报告基因实验验证miR-2355-3p与SERPINA3的相关性。qRT-PCR和Western blot检测FADU细胞中SERPINA3 mRNA和蛋白的表达。结果:miR-2355-3p在口腔麟状细胞癌中高表达。高水平miR-2355-3p的口腔鳞状细胞癌患者预后较差。miR-2355-3p预测口腔鳞癌的AUC为0.864(95%CI:0.798~0.931)。miR-2355-3p inhibitor下调miR-2355-3p表达。电离辐射(ionizing radiation, IR)处理抑制FADU细胞活性和增殖,促进细胞凋亡。转染miR-2355-3p inhibitor后,miR-2355-3p inhibitor进一步抑制FADU细胞活性和增殖,促进细胞凋亡。miR-2355-3p可直接靶向SERPINA3。miR-2355-3p inhibitor促进FADU细胞SERPINA3 mRNA和蛋白的表达。结论:miR-2355-3p通过靶向SERPINA3增强口腔鳞状细胞癌细胞的放射敏感性。
文摘目的:丝氨酸蛋白酶抑制剂A3(SerpinA3)在急性肾损伤(AKI)中的诊断及其预后价值。方法:前瞻性纳入广东省人民医院重症监护病房(ICU)收治的AKI患者(AKI组)93例和同期ICU非AKI患者(对照组)89例,用ELISA法检测患者的血液和尿液SerpinA3。收集患者临床资料及实验室检测数据。采用Spearman法分析血SerpinA3、尿SerpinA3与临床指标的相关性。对AKI患者随访28 d,用受试者工作曲线(ROC)和生存曲线对患者28 d存活及死亡进行分析。结果:AKI患者血SerpinA3[158250(107025,259575)ng/mL vs 125850(80775,196575)ng/mL,P<0.05]和尿SerpinA3[1618(678.8,5496)ng/mL vs 345.0(173.8,675.0)ng/mL,P<0.05]均较非AKI组显著增高。Spearman分析显示,尿SerpinA3与血清肌酐呈正相关(r=0.213,P<0.05)。尿SerpinA3在预测AKI患者的28 dd内病死率ROC曲线下面积为0.8,敏感度和特异度分别为72.73%和77.24%。Kaplan-Meier生存曲线分析结果显示,发生AKI时尿SerpinA3>5496 ng/mL的患者,28 d内生存率显著降低,预后较差。结论:SerpinA3对AKI诊断和预测患者预后有一定的价值,可作为AKI患者诊断和预后判断的生物学标志物。
文摘Dysregulation of the Wnt pathway has been extensively studied in multiple diseases,including some angiogenic disorders.Wnt signaling activation is a major stimulator in pathological angiogenesis and thus,Wnt antagonists are believed to have therapeutic potential for neovascular disorders.Actually,some Wnt antagonists have been identified directly from the anti-angiogenic factor family.This review summarizes the recent progress toward understanding of the roles of Wnt pathway antagonists in angiogenic regulation and their mechanism of action,and exploring their therapeutic potential.
文摘本研究旨在克隆西农萨能奶山羊SERPINA1基因的CDS区,采用生物软件和在线预测工具进行生物信息学分析,通过实时荧光定量PCR技术检测SERPINA1基因在西农萨能奶山羊各组织间mRNA的表达水平。根据GenBank中山羊SERPINA1基因CDS区序列(登录号:XM_018066209.1),利用Primer Premier 5.0软件设计特异性引物,RT-PCR扩增目的基因,构建原核表达载体测序后对序列进行生物信息学分析;采集西农萨能奶山羊心脏、肝脏、脾脏、肺脏、乳腺、肾脏、肌肉、瘤胃和小肠组织,提取组织RNA,反转录为cDNA模板,设计特异性定量引物,进行实时荧光定量PCR,检测SERPINA1基因在不同组织中的表达差异。结果显示,西农萨能奶山羊SERPINA1基因CDS区全长1326 bp,编码441个氨基酸;同源性比对分析显示,西农萨能奶山羊与山羊、绵羊、牛和小鼠SERPINA1基因核苷酸序列同源性分别为100%、98.6%、95.7%和71.6%,与山羊亲缘关系最近,其次是绵羊。SERPINA1蛋白分子质量为48.71 ku,等电点为5.71,为跨膜亲水蛋白;SERPINA1氨基酸序列分别有62个磷酸化位点,3个跨膜区结构。组织表达分析显示,SERPINA1基因在西农萨能奶山羊肝脏组织中显著高表达(P<0.05),其次是乳腺组织,在肺脏组织中表达量最低。研究结果为进一步探究SERPINA1基因在奶山羊乳蛋白合成代谢中的作用提供理论依据。
基金Supported by The Latvian Council of Science,National Project,Nos.09.1384 and 10.0010.02
文摘AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene(mutation): ATP7B(H1069Q), HFE(C282Y, H63D),UGT1A1(TA)7, and SERPINA1(PiZ)] were detected by polymerase chain reaction(PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61(76%), 7(9%), and 12(15%) patients, respectively. Among all 86 patients, 50(58%) reached an early viral response and 70(81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls(patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The(TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels(beta regression coefficient =-295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.
