AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/...AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.展开更多
BACKGROUND Early gastric cancer(EGC), compared with advanced gastric cancer(AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biom...BACKGROUND Early gastric cancer(EGC), compared with advanced gastric cancer(AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method.AIM To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs(miRNAs) in EGC and AGC and compared them with those in benign gastritis(BG).METHODSWe examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori(H. pylori)-negative gastritis(Control-1), and H. pylori-positive atrophic gastritis(Control-2).To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups.RESULTS Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis(Control-1) and H. pyloripositive atrophic gastritis(Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs,miR-7641, miR-425-5 p, miR-1180-3 p and miR-122-5 p, were used to effectively distinguish the Cancer group(EGC + AGC) from the Control group [area under the curve(AUC) = 0.799, 95% confidence interval(CI): 0.691-0.908, P < 0.001].Additionally, miR-425-5 p, miR-24-3 p, miR-1180-3 p and miR-122-5 p were utilized to distinguish EGC from the Control group(AUC = 0.829, 95%CI: 0.657-1.000, P =0.001). Moreover, the miR-24-3 p expression level in EGC was lower than that in the AGC(AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5 p expression level in EGC was significantly higher than that in AGC(AUC = 0.791,95%CI: 0.574-1.000, P = 0.024).CONCLUSION The differentially expressed circulatory plasma miR-425-5 p, miR-1180-3 p, miR-122-5 p, miR-24-3 p and miR-4632-5 p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.展开更多
目的研究脂多糖(LPS)和植物血凝素(PHA)两种淋巴细胞多克隆激活剂对小鼠外周血单个核细胞(PBMC)中microRNA(miRNA)水平的影响。方法分别采用100 ng/m L LPS刺激培养1、2 h的小鼠PBMC,2.5μg/m L PHA刺激培养2、4 h的小鼠PBMC。应用实时...目的研究脂多糖(LPS)和植物血凝素(PHA)两种淋巴细胞多克隆激活剂对小鼠外周血单个核细胞(PBMC)中microRNA(miRNA)水平的影响。方法分别采用100 ng/m L LPS刺激培养1、2 h的小鼠PBMC,2.5μg/m L PHA刺激培养2、4 h的小鼠PBMC。应用实时荧光定量PCR检测培养细胞和上清中miR-9、miR-122-3p、miR-181d及miR-342-3p的表达水平。结果与相应空白对照组相比,LPS刺激1 h或2 h后,培养上清及PBMC中miR-9、miR-122-3p、miR-181d及miR-342-3p的表达水平未见明显改变。PHA刺激未改变培养上清和PBMC中miR-9、miR-122-3p及miR-342-3p的水平,但显著上调培养上清和PBMC中miR-181d的水平。PHA刺激4 h组与PHA刺激2 h组间,miR-181d表达水平未见明显差异。结论 PHA刺激可促进小鼠PBMC中miR-181d的表达与分泌。展开更多
目的:探讨不同microRNA的表达及评估血浆microRNA作为早期乳腺癌诊断的新标志物的价值。方法:我们收集了49例早期乳腺癌的术前血浆作为实验样本和36例健康女性血浆作为对照样本。应用反转录和实时荧光定量聚合酶链反应,我们检测miR-21,m...目的:探讨不同microRNA的表达及评估血浆microRNA作为早期乳腺癌诊断的新标志物的价值。方法:我们收集了49例早期乳腺癌的术前血浆作为实验样本和36例健康女性血浆作为对照样本。应用反转录和实时荧光定量聚合酶链反应,我们检测miR-21,miR-205,miR-222这三个候选基因的相对表达量并分析了这三个候选microRNA表达与临床病理特征的关系。结果:我们发现,与健康对照相比,miR-21(1.565,P=0.022)and miR-222(2.258,P<0.001)在乳腺癌病人血浆中的表达明显升高,而miR-205(0.591,P=0.001)在乳腺癌病人血浆中的表达明显下降。并且在临床病例资料数据的比较中,miR-21(P=0.0101)在乳腺癌病人中的表达水平与雌激素受体和孕激素受体相关。血浆中miR-222的表达水平在肿瘤不同分期中明显不同。结论:本实验证明miR-21,miR-205 and miR-222的表达水平与乳腺癌的病理特征明显相关,可以作为乳腺癌的潜在标志物。展开更多
目的探讨microRNA-432(miR-432)在T2DM患者外周血清中的表达及其与IS的关系。方法收集在我院就诊的T2DM前期患者(n=19)、T2DM患者(n=23)和健康志愿者(NC组,n=20)外周血液标本,qRT-PCR检测miR-432水平,分析其与糖脂代谢、炎症因子及与IR...目的探讨microRNA-432(miR-432)在T2DM患者外周血清中的表达及其与IS的关系。方法收集在我院就诊的T2DM前期患者(n=19)、T2DM患者(n=23)和健康志愿者(NC组,n=20)外周血液标本,qRT-PCR检测miR-432水平,分析其与糖脂代谢、炎症因子及与IR的相关性。结果外周血中miR-432在NC组、T2DM前期组和T2DM组中呈下降趋势(1.00 vs 0.66 vs 0.35,P<0.05)。Pearson相关分析显示,miR-432与TC、LDL-C、载脂蛋白B/载脂蛋白A-1(ApoB/ApoA-1)、FPG、HOMA-IR、高敏C反应蛋白(hsC-RP)呈负相关,与ApoA-1、FIns和HDL-C呈正相关(P<0.05)。多元线性回归分析分析显示,BMI(β=0.465,95%CI=0.005~0.019,P=0.001)和miR-432(β=0.254,95%CI=0.039~0.146,P=0.045)是IS下降的独立影响因素。结论 miR-432在T2DM前期和T2DM患者外周血中下降,可能通过对糖脂代谢的影响参与IS的调节。展开更多
基金Supported by PHS grant DK075635 to Szabo G and McNeil Consumer Healthcare, a division of McNeil-PCC Inc. to Ward J
文摘AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.
基金Supported by the Health Industry Research Project of Gansu Province,No.GSWSKY2017-26the Gansu Province Science Foundation for Distinguished Young Scholars,No.1606RJDA317+1 种基金the Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province,No.zdsyskfkt-201704the Foundation of The First Hospital of Lanzhou University,No.ldyyyn2015-16
文摘BACKGROUND Early gastric cancer(EGC), compared with advanced gastric cancer(AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method.AIM To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs(miRNAs) in EGC and AGC and compared them with those in benign gastritis(BG).METHODSWe examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori(H. pylori)-negative gastritis(Control-1), and H. pylori-positive atrophic gastritis(Control-2).To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups.RESULTS Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis(Control-1) and H. pyloripositive atrophic gastritis(Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs,miR-7641, miR-425-5 p, miR-1180-3 p and miR-122-5 p, were used to effectively distinguish the Cancer group(EGC + AGC) from the Control group [area under the curve(AUC) = 0.799, 95% confidence interval(CI): 0.691-0.908, P < 0.001].Additionally, miR-425-5 p, miR-24-3 p, miR-1180-3 p and miR-122-5 p were utilized to distinguish EGC from the Control group(AUC = 0.829, 95%CI: 0.657-1.000, P =0.001). Moreover, the miR-24-3 p expression level in EGC was lower than that in the AGC(AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5 p expression level in EGC was significantly higher than that in AGC(AUC = 0.791,95%CI: 0.574-1.000, P = 0.024).CONCLUSION The differentially expressed circulatory plasma miR-425-5 p, miR-1180-3 p, miR-122-5 p, miR-24-3 p and miR-4632-5 p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.
基金Qingdao Science and Technology Project(08-2-1-4-nsh)~~
文摘目的:探讨不同microRNA的表达及评估血浆microRNA作为早期乳腺癌诊断的新标志物的价值。方法:我们收集了49例早期乳腺癌的术前血浆作为实验样本和36例健康女性血浆作为对照样本。应用反转录和实时荧光定量聚合酶链反应,我们检测miR-21,miR-205,miR-222这三个候选基因的相对表达量并分析了这三个候选microRNA表达与临床病理特征的关系。结果:我们发现,与健康对照相比,miR-21(1.565,P=0.022)and miR-222(2.258,P<0.001)在乳腺癌病人血浆中的表达明显升高,而miR-205(0.591,P=0.001)在乳腺癌病人血浆中的表达明显下降。并且在临床病例资料数据的比较中,miR-21(P=0.0101)在乳腺癌病人中的表达水平与雌激素受体和孕激素受体相关。血浆中miR-222的表达水平在肿瘤不同分期中明显不同。结论:本实验证明miR-21,miR-205 and miR-222的表达水平与乳腺癌的病理特征明显相关,可以作为乳腺癌的潜在标志物。
文摘目的探讨microRNA-432(miR-432)在T2DM患者外周血清中的表达及其与IS的关系。方法收集在我院就诊的T2DM前期患者(n=19)、T2DM患者(n=23)和健康志愿者(NC组,n=20)外周血液标本,qRT-PCR检测miR-432水平,分析其与糖脂代谢、炎症因子及与IR的相关性。结果外周血中miR-432在NC组、T2DM前期组和T2DM组中呈下降趋势(1.00 vs 0.66 vs 0.35,P<0.05)。Pearson相关分析显示,miR-432与TC、LDL-C、载脂蛋白B/载脂蛋白A-1(ApoB/ApoA-1)、FPG、HOMA-IR、高敏C反应蛋白(hsC-RP)呈负相关,与ApoA-1、FIns和HDL-C呈正相关(P<0.05)。多元线性回归分析分析显示,BMI(β=0.465,95%CI=0.005~0.019,P=0.001)和miR-432(β=0.254,95%CI=0.039~0.146,P=0.045)是IS下降的独立影响因素。结论 miR-432在T2DM前期和T2DM患者外周血中下降,可能通过对糖脂代谢的影响参与IS的调节。
