目的:探讨microRNA-29c对人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2)生物学特性的影响。方法:培养1种人正常胰腺上皮细胞(HPDE)及4种人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2),采用real-time PCR法观察5种细胞系...目的:探讨microRNA-29c对人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2)生物学特性的影响。方法:培养1种人正常胰腺上皮细胞(HPDE)及4种人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2),采用real-time PCR法观察5种细胞系中microRNA-29c的表达差异,以microRNA-29c过表达腺病毒感染的PANC-1和MIA Pa Ca2细胞作为实验组,以空载体感染的PANC-1和MIA Pa Ca2细胞作为阴性对照组,采用细胞划痕实验、Transwell法检测两组细胞体外侵袭能力,Western blot检测两组细胞上皮间充质转化(EMT)相关蛋白波形蛋白(Vimentin)及E-钙粘蛋白(E-cadherin)的表达。结果:real-time-PCR显示各胰腺癌细胞系中microRNA-29c水平明显低于正常胰腺细胞系(P<0.05),细胞划痕实验发现感染腺病毒48 h后实验组PANC-1、MIA Pa Ca-2细胞的迁移距离明显短于阴性对照组(P<0.05),Transwell小室细胞侵袭实验发现实验组PANC-1和MIA Pa Ca-2细胞侵袭数量明显低于阴性对照组(P<0.05);Western blot蛋白免疫印迹结果显示PANC-1和MIA Pa Ca-2细胞过表达microRNA-29c后,Vimentin表达减少,E-cadherin表达增加。结论:microRNA-29c的过表达可有效抑制胰腺癌细胞的体外侵袭与转移,可能与Vimentin表达减少,E-cadherin表达增加有关,有望成为胰腺癌生物治疗的潜在靶点。展开更多
Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, do...Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, does not encode viral mi RNA. However, HCV infection alters the expression of host mi RNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host mi RNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular m RNAs. Increasing evidence demonstrates that mi RNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host m RNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host mi RNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special mi RNAs are closely correlated with liver-specific disease progression and the changed levels of mi RNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCVinfected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.展开更多
Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the on...Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers.The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear.In the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers.Here,we briefly describe the current knowledge about microRNAs' involvement in HCV-related molecular oncogenesis.We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HCV genome.Some of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of patients.What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.展开更多
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
Austenite grain size is an important influence factor for ductility of steel at high temperatures during continuous casting. Thermodynamic and kinetics calculations were performed to analyze the characteristics of Ti(...Austenite grain size is an important influence factor for ductility of steel at high temperatures during continuous casting. Thermodynamic and kinetics calculations were performed to analyze the characteristics of Ti(C,N) precipitates formed during the continuous casting of micro-alloyed steel. Based on Andersen-Grong equation, a coupling model of second phase precipitation and austenite grain growth has been established, and the influence of second precipitates on austenite grain growth under different cooling rates is discussed. Calculations show that the final sizes of austenite grains are 2.155, 1.244, 0.965, 0.847 and 0.686 mm, respectively, under the cooling rate of 1, 3, 5, 7, and 10 ℃·s^(-1), when ignoring the pinning effect of precipitation on austenite growth. Whereas, if taking the pinning effect into consideration, the grain growth remains stable from 1,350 ℃, the calculated final sizes of austenite grains are 1.46, 1.02, 0.80, 0.67 and 0.57 mm, respectively. The sizes of final Ti(C,N) precipitates are 137, 79, 61, 51 and 43 nm, respectively, with the increase of cooling rate from 1 to 10 ℃·s^(-1). Model validation shows that the austenite size under different cooling rates coincided with the calculation results. Finally, the corresponding measures to strengthen cooling intensity at elevated temperature are proposed to improve the ductility and transverse crack of slab.展开更多
During the Folin Ciocalteu (F-C) micro-assay for the determination of phenolics in the presence of methanol, fine solids can form. In a previous paper, we hypothesized that the interference from alcohol on the F-C rea...During the Folin Ciocalteu (F-C) micro-assay for the determination of phenolics in the presence of methanol, fine solids can form. In a previous paper, we hypothesized that the interference from alcohol on the F-C reaction can be minimized depending on the particular procedure used to reach the alkalinity condition. In order to demonstrate our hypothesis we studied, by spectrophotometrically monitoring, the time-behaviour of the reactions carried out in the presence of different methanol concentrations at the same alkalinity condition from two protocols. The results showed that the interfering effect of methanol on the F-C micro-method can be affect and even prevented depending on working conditions. In particular, the formation of fine solids can be delayed, slowed down and prevented depending on the initial carbonate concentration used. We have explained why the initial carbonate concentration, used to reach the final alkalinity condition, plays an important role in the F-C reaction carried out in the presence of methanol. Moreover, the results from real-time monitoring showed that, differently from traditional F-C procedure, our procedure allows us to carry out the F-C micro method in the presence of 6% methanol, as an extreme concentration, reading the absorbance at real time 24 min. The real-time monitoring of absorbance can be considered as a useful means to explore the effect of other parameters on precipitate formation caused by the presence of methanol in the F-C reaction.展开更多
The cutting performance of particulate reinforced me tallic matrix composites(PRMMCs) SiC p/Al in ultrasonic vibration cutting and c ommon cutting with carbide tools and PCD tools was researched in the paper. Mic rost...The cutting performance of particulate reinforced me tallic matrix composites(PRMMCs) SiC p/Al in ultrasonic vibration cutting and c ommon cutting with carbide tools and PCD tools was researched in the paper. Mic rostructure of machined surface was described, the relation between cutting para meters and surface roughness was presented, and characteristic of the surface re mained stress was also presented. Furthermore, wear regularity and abrasion resi stance ability of tools in ultrasonic vibration cutting and common cutting o f PRMMCs were discussed in detail. The test results show: (1) The surface config urations are obviously different when using different tools to machine such PRMM Cs. The surface machined with carbide tools looks luminous and orderly and there are seldom surface defects on it. The reason is that the soft basal body is apt to flow during cutting, therefore a layer of Al matrix film covers machined sur face. On the contrary, the surface machined with PCD tools looks lackluster. But the profile of machined surface is very clear. Superfine grooves, pits and blac k reinforce particulates can be seen easily without obvious Al film. (2) Because of unstable cutting process in common cutting, the surface is easy to produce s ome defects such as burrs, built-up edges and so on so that the quality of surf ace becomes very poor. Vibration cutting can reduce the influence of tearing, pl astic deformation and built-up edge in cutting and can restrain flutter so as t o make cutting process more stable. Therefore, surface roughness of vibration cu tting is better than that of common cutting. (3) There is an optimum value of fe ed rate in vibration cutting of PRMMCs due to the influence of material characte ristics. Whether feed rate is more than or less than this optimum value, surface roughness will increase. (4) According to analyzing the wear rate of tools in v ibration cutting PRMMCs, it can be concluded that abrasion resistance of tools w ill be improved remarkably when vibration cutting composites have a lower pe rcentage of reinforce particulate. If the percentage of reinforce particulate is higher, the influence on abrasion resistance of carbide tool in vibration cut ting will not be obvious. The research result indicates that vibration cutting effect has a close relation with material characteristics.展开更多
文摘目的:探讨microRNA-29c对人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2)生物学特性的影响。方法:培养1种人正常胰腺上皮细胞(HPDE)及4种人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2),采用real-time PCR法观察5种细胞系中microRNA-29c的表达差异,以microRNA-29c过表达腺病毒感染的PANC-1和MIA Pa Ca2细胞作为实验组,以空载体感染的PANC-1和MIA Pa Ca2细胞作为阴性对照组,采用细胞划痕实验、Transwell法检测两组细胞体外侵袭能力,Western blot检测两组细胞上皮间充质转化(EMT)相关蛋白波形蛋白(Vimentin)及E-钙粘蛋白(E-cadherin)的表达。结果:real-time-PCR显示各胰腺癌细胞系中microRNA-29c水平明显低于正常胰腺细胞系(P<0.05),细胞划痕实验发现感染腺病毒48 h后实验组PANC-1、MIA Pa Ca-2细胞的迁移距离明显短于阴性对照组(P<0.05),Transwell小室细胞侵袭实验发现实验组PANC-1和MIA Pa Ca-2细胞侵袭数量明显低于阴性对照组(P<0.05);Western blot蛋白免疫印迹结果显示PANC-1和MIA Pa Ca-2细胞过表达microRNA-29c后,Vimentin表达减少,E-cadherin表达增加。结论:microRNA-29c的过表达可有效抑制胰腺癌细胞的体外侵袭与转移,可能与Vimentin表达减少,E-cadherin表达增加有关,有望成为胰腺癌生物治疗的潜在靶点。
基金Supported by National Natural Science Foundation of China No.81321004 and No.81322050National Mega-Project for“R&D for Innovative Drugs”+3 种基金Ministry of Science and TechnologyChina No.2012ZX09301-002-001Ministry of EducationChina No.NCET-12-0072
文摘Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, does not encode viral mi RNA. However, HCV infection alters the expression of host mi RNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host mi RNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular m RNAs. Increasing evidence demonstrates that mi RNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host m RNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host mi RNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special mi RNAs are closely correlated with liver-specific disease progression and the changed levels of mi RNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCVinfected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.
基金Supported by Grants from 2015 Post-Doc fellowship "Fondazione Umberto Veronesi"(to Gragnani L)2015 AIRC fellowship(to Fognani E)FIRE(to Piluso A)
文摘Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers.The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear.In the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers.Here,we briefly describe the current knowledge about microRNAs' involvement in HCV-related molecular oncogenesis.We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HCV genome.Some of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of patients.What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.
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.
基金supported by the National Natural Science Foundation of China(No.51504172)and(No.51474163)China Postdoctoral Science Foundation(No.2015M572212)
文摘Austenite grain size is an important influence factor for ductility of steel at high temperatures during continuous casting. Thermodynamic and kinetics calculations were performed to analyze the characteristics of Ti(C,N) precipitates formed during the continuous casting of micro-alloyed steel. Based on Andersen-Grong equation, a coupling model of second phase precipitation and austenite grain growth has been established, and the influence of second precipitates on austenite grain growth under different cooling rates is discussed. Calculations show that the final sizes of austenite grains are 2.155, 1.244, 0.965, 0.847 and 0.686 mm, respectively, under the cooling rate of 1, 3, 5, 7, and 10 ℃·s^(-1), when ignoring the pinning effect of precipitation on austenite growth. Whereas, if taking the pinning effect into consideration, the grain growth remains stable from 1,350 ℃, the calculated final sizes of austenite grains are 1.46, 1.02, 0.80, 0.67 and 0.57 mm, respectively. The sizes of final Ti(C,N) precipitates are 137, 79, 61, 51 and 43 nm, respectively, with the increase of cooling rate from 1 to 10 ℃·s^(-1). Model validation shows that the austenite size under different cooling rates coincided with the calculation results. Finally, the corresponding measures to strengthen cooling intensity at elevated temperature are proposed to improve the ductility and transverse crack of slab.
文摘During the Folin Ciocalteu (F-C) micro-assay for the determination of phenolics in the presence of methanol, fine solids can form. In a previous paper, we hypothesized that the interference from alcohol on the F-C reaction can be minimized depending on the particular procedure used to reach the alkalinity condition. In order to demonstrate our hypothesis we studied, by spectrophotometrically monitoring, the time-behaviour of the reactions carried out in the presence of different methanol concentrations at the same alkalinity condition from two protocols. The results showed that the interfering effect of methanol on the F-C micro-method can be affect and even prevented depending on working conditions. In particular, the formation of fine solids can be delayed, slowed down and prevented depending on the initial carbonate concentration used. We have explained why the initial carbonate concentration, used to reach the final alkalinity condition, plays an important role in the F-C reaction carried out in the presence of methanol. Moreover, the results from real-time monitoring showed that, differently from traditional F-C procedure, our procedure allows us to carry out the F-C micro method in the presence of 6% methanol, as an extreme concentration, reading the absorbance at real time 24 min. The real-time monitoring of absorbance can be considered as a useful means to explore the effect of other parameters on precipitate formation caused by the presence of methanol in the F-C reaction.
文摘The cutting performance of particulate reinforced me tallic matrix composites(PRMMCs) SiC p/Al in ultrasonic vibration cutting and c ommon cutting with carbide tools and PCD tools was researched in the paper. Mic rostructure of machined surface was described, the relation between cutting para meters and surface roughness was presented, and characteristic of the surface re mained stress was also presented. Furthermore, wear regularity and abrasion resi stance ability of tools in ultrasonic vibration cutting and common cutting o f PRMMCs were discussed in detail. The test results show: (1) The surface config urations are obviously different when using different tools to machine such PRMM Cs. The surface machined with carbide tools looks luminous and orderly and there are seldom surface defects on it. The reason is that the soft basal body is apt to flow during cutting, therefore a layer of Al matrix film covers machined sur face. On the contrary, the surface machined with PCD tools looks lackluster. But the profile of machined surface is very clear. Superfine grooves, pits and blac k reinforce particulates can be seen easily without obvious Al film. (2) Because of unstable cutting process in common cutting, the surface is easy to produce s ome defects such as burrs, built-up edges and so on so that the quality of surf ace becomes very poor. Vibration cutting can reduce the influence of tearing, pl astic deformation and built-up edge in cutting and can restrain flutter so as t o make cutting process more stable. Therefore, surface roughness of vibration cu tting is better than that of common cutting. (3) There is an optimum value of fe ed rate in vibration cutting of PRMMCs due to the influence of material characte ristics. Whether feed rate is more than or less than this optimum value, surface roughness will increase. (4) According to analyzing the wear rate of tools in v ibration cutting PRMMCs, it can be concluded that abrasion resistance of tools w ill be improved remarkably when vibration cutting composites have a lower pe rcentage of reinforce particulate. If the percentage of reinforce particulate is higher, the influence on abrasion resistance of carbide tool in vibration cut ting will not be obvious. The research result indicates that vibration cutting effect has a close relation with material characteristics.
