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
目的观察冠状动脉再灌注治疗对急性心肌梗死(AMI)患者血浆外泌体微小RNA(miRNA,miR)差异表达的影响。方法选取2022年10月至11月于深圳市龙岗区第三人民医院确诊的3例老年男性AMI患者,进行冠状动脉再灌注治疗,留取患者入院时、术后2 h和...目的观察冠状动脉再灌注治疗对急性心肌梗死(AMI)患者血浆外泌体微小RNA(miRNA,miR)差异表达的影响。方法选取2022年10月至11月于深圳市龙岗区第三人民医院确诊的3例老年男性AMI患者,进行冠状动脉再灌注治疗,留取患者入院时、术后2 h和术后24 h静脉血,应用miRNA测序技术筛选3例患者血浆外泌体中共同差异表达miRNA后,对其靶基因进行生信分析,利用定量聚合酶链反应验证其中差异表达的miR-499a-5p。结果与入院时比较,术后2 h血浆外泌体miRNA有418个上调和406个下调,术后24 h血浆外泌体miRNA有320个上调和225个下调(P<0.05);与术后2 h比较,术后24 h血浆外泌体miRNA有344个上调和350个下调(P<0.05)。Kyoto Encyclopedia of Genes and Genomes富集分析显示,差异表达的miRNA富集在磷脂酰肌醇-3-激酶-蛋白激酶B、缺氧诱导因子1和血管平滑肌收缩等通路。Gene Ontology富集分析显示,差异表达的miRNA靶基因分子功能方面主要富集于蛋白结合和DNA结合;细胞组分方面主要富集于细胞膜和细胞质;生物学过程方面主要富集于信号转导和DNA模板转录。术后2 h miR-499a-5p水平显著低于入院时[(0.577±0.020)vs(1.000±0.023),P<0.05],术后24 h miR-499a-5p水平显著低于术后2 h[(0.068±0.006)vs(0.577±0.020),P<0.05]。结论血浆外泌体miRNA可作为早期诊断老年AMI患者和预测冠状动脉再灌注治疗效果的生物标志物。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.
文摘目的观察冠状动脉再灌注治疗对急性心肌梗死(AMI)患者血浆外泌体微小RNA(miRNA,miR)差异表达的影响。方法选取2022年10月至11月于深圳市龙岗区第三人民医院确诊的3例老年男性AMI患者,进行冠状动脉再灌注治疗,留取患者入院时、术后2 h和术后24 h静脉血,应用miRNA测序技术筛选3例患者血浆外泌体中共同差异表达miRNA后,对其靶基因进行生信分析,利用定量聚合酶链反应验证其中差异表达的miR-499a-5p。结果与入院时比较,术后2 h血浆外泌体miRNA有418个上调和406个下调,术后24 h血浆外泌体miRNA有320个上调和225个下调(P<0.05);与术后2 h比较,术后24 h血浆外泌体miRNA有344个上调和350个下调(P<0.05)。Kyoto Encyclopedia of Genes and Genomes富集分析显示,差异表达的miRNA富集在磷脂酰肌醇-3-激酶-蛋白激酶B、缺氧诱导因子1和血管平滑肌收缩等通路。Gene Ontology富集分析显示,差异表达的miRNA靶基因分子功能方面主要富集于蛋白结合和DNA结合;细胞组分方面主要富集于细胞膜和细胞质;生物学过程方面主要富集于信号转导和DNA模板转录。术后2 h miR-499a-5p水平显著低于入院时[(0.577±0.020)vs(1.000±0.023),P<0.05],术后24 h miR-499a-5p水平显著低于术后2 h[(0.068±0.006)vs(0.577±0.020),P<0.05]。结论血浆外泌体miRNA可作为早期诊断老年AMI患者和预测冠状动脉再灌注治疗效果的生物标志物。
