BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important r...BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.展开更多
Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, progn...Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.展开更多
Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome...Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome(Met S)show decreased vitality.A growing number of micro RNAs(mi RNAs)are recognized as key modulators of senescence,but their role in regulating senescence in MSC in Mets is unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet(n=6 each).Next-generation mi RNA sequencing(mi RNA-seq)was performed to identify mi RNAs up-or down-regulated in Met S-MSC compare to Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We found the 7 upregulated mi RNAs,including mi R-27b,and 3 downregulated mi RNAs in Met S-MSCs,which regulate 35 SA genes,particularly MAPK signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions Met S modulate MSC expression of SA-mi RNAs that may play the role in modulating their senescence,and the p16 pathway in Met S-MSCs senescence is the primary pathway.展开更多
目的探讨胃癌患者血清miR-216b和miR-132水平表达与临床预后的关系。方法选取2018年1月~2020年2月在佳木斯市中心医院就诊的87例胃癌患者作为胃癌组,选择同期87例健康体检者作为对照组。实时荧光定量PCR(quantitative real-time PCR,qRT...目的探讨胃癌患者血清miR-216b和miR-132水平表达与临床预后的关系。方法选取2018年1月~2020年2月在佳木斯市中心医院就诊的87例胃癌患者作为胃癌组,选择同期87例健康体检者作为对照组。实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测血清中miR-216b和miR-132表达水平,分析胃癌患者血清miR-216b和miR-132表达水平与临床病理特征的关系。根据胃癌患者随访期间的生存或死亡情况,将胃癌患者分为预后良好组(生存,n=51)和预后不良组(死亡,n=36),用受试者工作特征(receiver operating characteristic,ROC)曲线分析血清miR-216b和miR-132表达水平对胃癌患者预后的预测价值;COX回归分析影响胃癌患者预后的因素。结果与对照组比较,胃癌组血清中miR-216b(0.69±0.20 vs 1.02±0.24)和miR-132(0.73±0.19 vs 1.01±0.22)表达水平降低,差异具有统计学意义(t=9.853,8.984,均P<0.001)。分化程度为低分化、TNM分期为III±IV期、有淋巴结转移、有远处转移的胃癌患者血清miR-216b,miR-132表达水平低于分化程度为中、高分化、TNM分期为I±II期、无淋巴结转移、无远处转移的胃癌患者,差异具有统计学意义(t=6.266,3.412,2.890,2.723;4.999,3.734,4.180,5.502,均P<0.05)。与预后良好组比较,预后不良组胃癌患者血清中miR-216b(0.56±0.16 vs 0.78±0.23)和miR-132(0.60±0.11 vs 0.82±0.25)表达水平降低,差异具有统计学意义(t=4.952,4.946,均P<0.001)。血清miR-216b,miR-132及二者联合预测胃癌患者预后的曲线下面积(area under the cure,AUC)分别为0.797(95%CI:0.706~0.889),0.832(95%CI:0.745~0.918)和0.900(95%CI:0.836~0.964);敏感度和特异度分别为83.3%,68.6%;97.2%,62.7%和79.4%,72.5%;当血清miR-216b,miR-132预测胃癌患者预后不良的截断值分别为0.66,0.76时,预测的敏感度较高。COX回归分析显示,miR-216b低表达、miR-132低表达、分化程度为低分化、TNM分期为III+IV期、有淋巴结转移、有远处转移是胃癌患者预后不良的危险因素(均P<0.05)。结论miR-216b和miR-132在胃癌患者血清中呈低表达,二者可作为预测胃癌患者预后的有效生物标志物。展开更多
基金Science and Technology Development Foundation(STDF),Project NO.3457(TC/4/Health/2010/hep-1.6)
文摘BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.
文摘Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.
基金Guangdong Provincial Center for clinical engineering of blood purification(507204531040)
文摘Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome(Met S)show decreased vitality.A growing number of micro RNAs(mi RNAs)are recognized as key modulators of senescence,but their role in regulating senescence in MSC in Mets is unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet(n=6 each).Next-generation mi RNA sequencing(mi RNA-seq)was performed to identify mi RNAs up-or down-regulated in Met S-MSC compare to Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We found the 7 upregulated mi RNAs,including mi R-27b,and 3 downregulated mi RNAs in Met S-MSCs,which regulate 35 SA genes,particularly MAPK signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions Met S modulate MSC expression of SA-mi RNAs that may play the role in modulating their senescence,and the p16 pathway in Met S-MSCs senescence is the primary pathway.
文摘目的探讨胃癌患者血清miR-216b和miR-132水平表达与临床预后的关系。方法选取2018年1月~2020年2月在佳木斯市中心医院就诊的87例胃癌患者作为胃癌组,选择同期87例健康体检者作为对照组。实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测血清中miR-216b和miR-132表达水平,分析胃癌患者血清miR-216b和miR-132表达水平与临床病理特征的关系。根据胃癌患者随访期间的生存或死亡情况,将胃癌患者分为预后良好组(生存,n=51)和预后不良组(死亡,n=36),用受试者工作特征(receiver operating characteristic,ROC)曲线分析血清miR-216b和miR-132表达水平对胃癌患者预后的预测价值;COX回归分析影响胃癌患者预后的因素。结果与对照组比较,胃癌组血清中miR-216b(0.69±0.20 vs 1.02±0.24)和miR-132(0.73±0.19 vs 1.01±0.22)表达水平降低,差异具有统计学意义(t=9.853,8.984,均P<0.001)。分化程度为低分化、TNM分期为III±IV期、有淋巴结转移、有远处转移的胃癌患者血清miR-216b,miR-132表达水平低于分化程度为中、高分化、TNM分期为I±II期、无淋巴结转移、无远处转移的胃癌患者,差异具有统计学意义(t=6.266,3.412,2.890,2.723;4.999,3.734,4.180,5.502,均P<0.05)。与预后良好组比较,预后不良组胃癌患者血清中miR-216b(0.56±0.16 vs 0.78±0.23)和miR-132(0.60±0.11 vs 0.82±0.25)表达水平降低,差异具有统计学意义(t=4.952,4.946,均P<0.001)。血清miR-216b,miR-132及二者联合预测胃癌患者预后的曲线下面积(area under the cure,AUC)分别为0.797(95%CI:0.706~0.889),0.832(95%CI:0.745~0.918)和0.900(95%CI:0.836~0.964);敏感度和特异度分别为83.3%,68.6%;97.2%,62.7%和79.4%,72.5%;当血清miR-216b,miR-132预测胃癌患者预后不良的截断值分别为0.66,0.76时,预测的敏感度较高。COX回归分析显示,miR-216b低表达、miR-132低表达、分化程度为低分化、TNM分期为III+IV期、有淋巴结转移、有远处转移是胃癌患者预后不良的危险因素(均P<0.05)。结论miR-216b和miR-132在胃癌患者血清中呈低表达,二者可作为预测胃癌患者预后的有效生物标志物。
