AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene ...AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000TM. At 48-72 h after siRNAs transfection, MTT assay,RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.RESULTS: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2cells.CONCLUSION: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method,synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.展开更多
The thiopurine drugs,6-mercaptopurine(6-MP) and azathioprine,are efficacious in the arsenal of inflammatory bowel disease(IBD) therapy.Previous reports indicate that 6-thioguanine nucleotide(6-TGN) levels correlate wi...The thiopurine drugs,6-mercaptopurine(6-MP) and azathioprine,are efficacious in the arsenal of inflammatory bowel disease(IBD) therapy.Previous reports indicate that 6-thioguanine nucleotide(6-TGN) levels correlate with therapeutic efficacy,whereas high 6-methylmercaptopurine(6-MMP) levels are associated with hepatotoxicity and myelotoxicity.Due to their complex metabolism,there is wide individual variation in patient response therein,both in achieving therapeutic drug levels as well as in developing adverse reactions.Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects.In this report,we will review different approaches to administer the thiopurine medications,including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine;coadministration of thiopurine with allopurinol;co-administration of thiopurine with anti-tumor necrosis factor α;6-TGN administration;desensitization trials;and split dosing of 6-MP.展开更多
Heroin is considered potent and addictive and users are often stigmatised as the other. On the internet, however, hegemonic ideas about drugs can be resisted. This study elucidates how efforts to uormalise and demonis...Heroin is considered potent and addictive and users are often stigmatised as the other. On the internet, however, hegemonic ideas about drugs can be resisted. This study elucidates how efforts to uormalise and demonise heroin meet at a Swedish online message board (Flashback Forum). The study aims at analysing how heroin use is given meaning by discussants in a thread called "I will start with heroin". The data were perceived and structured as a collaborative, overarching narrative about when, why, and for whom heroin use can make sense. Discussants used stories about pleasure-seekers, miserable junkies, and self-medicating addicts to depict the activity as unproblematic and rational, problematic and irrational, or as problematic and rational. No stories about heroin use departed from the plot-lines of pleasure maximisation and pain minimisation. Results elucidate a discursive battle in which: (1) heroin use as minimisation of pain "wins" over heroin use as maximisation of pleasure; and (2) there is a general agreement that heroin use cannot be irrational and unproblematic at the same time. It is suggested that these features are central to contemporary drug discourse, and that they probably hinder public understanding of why people use heroin and therefore contribute to keep users stigmatised.展开更多
Traditionally, differentiation of syndromes of Traditional Chinese Medicine (TCM) mainly depends on the information obtained from four diagnosis methods. Now many physicochemical parameters are available in clinic. Th...Traditionally, differentiation of syndromes of Traditional Chinese Medicine (TCM) mainly depends on the information obtained from four diagnosis methods. Now many physicochemical parameters are available in clinic. There exists great correlation between TCM syndromes and physicochemical parameters. The objective of the paper is to analyze the correlation between TCM syndromes and physicochemical parameters quantitatively. Correlation analysis has been widely studied and many analysis methods have been developed. Mutual information based on entropy can measure arbitrary dependence between variables. It has been applied to many kinds of fields, especially to pattern recognition. But most works are restricted to discrete variables and little work has been done to study the relation between discrete and continuous variables. A novel algorithm is proposed to calculate the mutual information between discrete and continuous variables. It is used to analyze the correlation between TCM syndromes and physicochemical parameters.展开更多
基金Supported by the National Natural Science Foundation of China, No. 30371662
文摘AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000TM. At 48-72 h after siRNAs transfection, MTT assay,RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.RESULTS: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2cells.CONCLUSION: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method,synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.
基金Supported by Grant from Inflammatory Bowel and Immunobiology Research Institute,Cedars-Sinai Medical Center
文摘The thiopurine drugs,6-mercaptopurine(6-MP) and azathioprine,are efficacious in the arsenal of inflammatory bowel disease(IBD) therapy.Previous reports indicate that 6-thioguanine nucleotide(6-TGN) levels correlate with therapeutic efficacy,whereas high 6-methylmercaptopurine(6-MMP) levels are associated with hepatotoxicity and myelotoxicity.Due to their complex metabolism,there is wide individual variation in patient response therein,both in achieving therapeutic drug levels as well as in developing adverse reactions.Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects.In this report,we will review different approaches to administer the thiopurine medications,including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine;coadministration of thiopurine with allopurinol;co-administration of thiopurine with anti-tumor necrosis factor α;6-TGN administration;desensitization trials;and split dosing of 6-MP.
文摘Heroin is considered potent and addictive and users are often stigmatised as the other. On the internet, however, hegemonic ideas about drugs can be resisted. This study elucidates how efforts to uormalise and demonise heroin meet at a Swedish online message board (Flashback Forum). The study aims at analysing how heroin use is given meaning by discussants in a thread called "I will start with heroin". The data were perceived and structured as a collaborative, overarching narrative about when, why, and for whom heroin use can make sense. Discussants used stories about pleasure-seekers, miserable junkies, and self-medicating addicts to depict the activity as unproblematic and rational, problematic and irrational, or as problematic and rational. No stories about heroin use departed from the plot-lines of pleasure maximisation and pain minimisation. Results elucidate a discursive battle in which: (1) heroin use as minimisation of pain "wins" over heroin use as maximisation of pleasure; and (2) there is a general agreement that heroin use cannot be irrational and unproblematic at the same time. It is suggested that these features are central to contemporary drug discourse, and that they probably hinder public understanding of why people use heroin and therefore contribute to keep users stigmatised.
基金The research has been supported by National Basic Research Program of China(973 Grant 2003CB517106) MOSTProjects (No.2004DFB02100)
文摘Traditionally, differentiation of syndromes of Traditional Chinese Medicine (TCM) mainly depends on the information obtained from four diagnosis methods. Now many physicochemical parameters are available in clinic. There exists great correlation between TCM syndromes and physicochemical parameters. The objective of the paper is to analyze the correlation between TCM syndromes and physicochemical parameters quantitatively. Correlation analysis has been widely studied and many analysis methods have been developed. Mutual information based on entropy can measure arbitrary dependence between variables. It has been applied to many kinds of fields, especially to pattern recognition. But most works are restricted to discrete variables and little work has been done to study the relation between discrete and continuous variables. A novel algorithm is proposed to calculate the mutual information between discrete and continuous variables. It is used to analyze the correlation between TCM syndromes and physicochemical parameters.