OBJECTIVE To study the effect of the Twist gene on the migration of human hepatocellular carcinoma cells and the possible mechanisms involved. METHODS RT-PCR was used to detect expression of the Twist gene in primary ...OBJECTIVE To study the effect of the Twist gene on the migration of human hepatocellular carcinoma cells and the possible mechanisms involved. METHODS RT-PCR was used to detect expression of the Twist gene in primary (Hep11) and recurrent (Hep12) cell lines from the same HCC patient. Hep11 cells were stably transfected with Twist-cDNA, and Hep12 cells were transiently transfected with Twist RNAi plasmid. Cell migration assays were performed on Twist up-regulated Hep11 cells and Twist RNAi Hep12 cells. RT- PCR and Western blot were used to test the expression of EMT markers. RESULTS Twist was expressed higher level and had increased migration capability in recurrent Hep12 cells than those in primary Hep11 cells. Cell models (Twist-Hep11) in which Twist protein was steadily and highly expressed were obtained. Compared with pcDNA3-Hep11 cells, migration of Twist-Hep11 cells was clearly increased. However, migration of Twist RNAi (Si-Twist-Hep12) Hep12 cells were reduced. Overexpression of Twist in Hep11 cells promoted expression of N-cad and vimentin. CONCLUSION These results indicate that Twist promotes the migration of hepatocellular carcinoma cells in vitro and may play an important role in the upregulation of mesenchymal markers.展开更多
The effects of clinically relevant doses of commonly prescribed stimulants methylphenidate (MPH), d-am- phetamine (d-AMPH), and dl-AMPH or mixed amphetamine salts (MAS) such as Adderall, on short- and long-term ...The effects of clinically relevant doses of commonly prescribed stimulants methylphenidate (MPH), d-am- phetamine (d-AMPH), and dl-AMPH or mixed amphetamine salts (MAS) such as Adderall, on short- and long-term gene neuroadaptations in developing animals have not been widely investigated. In the present review, the effects of oral stimulant administration were compared with those of the subcutaneous or intra-peritoneal route. A selective set of stud- ies between 1979 and 2010, which incorporated in their design developmental period, clinically relevant doses of stimu- lants, and repeated daily doses were reviewed. These studies indicate that neuroadaptation to chronic stimulants includes blunting of stimulated immediate early gene expression, sensitivity of younger (prepubertal) brain to smaller dosages of stimulants, and the persistence of some effects, especially behavioral neuroadaptations, into adulthood. In addition, oral amphetamines (MAS) have more profound effects than does oral MPH. Further animal developmental studies are required to understand potential long-term neuroadaptations to low, daily oral doses of stimulants. Implications for clinical practice were also discussed.展开更多
OBJECTIVE:To investigate the molecular effect of Socheongryong Tang(SCRT,Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology.METHODS:Asthma was induced by intranasal inst...OBJECTIVE:To investigate the molecular effect of Socheongryong Tang(SCRT,Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology.METHODS:Asthma was induced by intranasal instillation of ovalbumin in mouse.After administration of SCRT on asthma-induced mouse,the expression of genes in lung tissue was measured using whole genome microarray.The functional implication of differentially expressed genes was performed using ontological analysis and the similarity of promoter structure of genes was also analyzed.RESULTS:Treatment of SCRT restored expression level of many up- or down-regulated genes in asthma model,and this recovery rate means SCRT could regulate a set of genes having specific TFBS binding sites.CONCLUSION:In this study,we identified a set of genes subjected to similar regulation by SCRT in asthma model in mice.展开更多
Buffering exogenous perturbation is crucial to maintain transcriptional homeostasis during development.While mi RNAs have been speculated to play a role in stability maintenance, previous studies seeking to check this...Buffering exogenous perturbation is crucial to maintain transcriptional homeostasis during development.While mi RNAs have been speculated to play a role in stability maintenance, previous studies seeking to check this conjecture focused on measurements of transcript levels at steady state or involved individual mi RNA targets. We measured whole-genome expression dynamics by introducing a transient perturbation and establishing a perturbation and recovery system in Drosophila larvae. We inhibited all transcription and assayed transcriptomes at several time points during recovery from inhibition. We performed these experiments in the wild type and mi RNA-deficient genetic backgrounds. Consistent with theories about mi RNAs’ function in stabilizing the transcriptome, we find that attenuating mi RNA expression leads to weak impairment in degradation of targets but strong destabilization of target genes when transcription is re-activated. We further fitted a model that captures the essential aspects of transcription dynamics in our experiments and found that the mi RNA target transcripts uniformly overshoot the original steady state as they recover from a general inhibition of transcription if global mi RNA levels are reduced. Collectively, our results provide experimental evidence for the idea that mi RNAs act cumulatively to stabilize the transcriptional regulatory network. We therefore found a promising approach to assess the effect of these molecules on transcription dynamics.展开更多
The dynamics of constitutive gene expression with delayed m RNA degradation is investigated, where the intrinsic noise caused by the small number of reactant molecules is introduced. It is found that the oscillatory b...The dynamics of constitutive gene expression with delayed m RNA degradation is investigated, where the intrinsic noise caused by the small number of reactant molecules is introduced. It is found that the oscillatory behavior claimed in previous investigations does not appear in the approximation of small time delay, and the steady state distribution still follows the Poisson law. Furthermore, we introduce the extrinsic noise induced by surrounding environment to explore the effects of this noise and time delay on the Fano factor. Based on a delay Langevin equation and the corresponding Fokker–Planck equation, the distribution of m RNA copy-number is achieved analytically. The time delay and extrinsic noise play similar roles in the gene expression system, that is, they are able to result in the deviation of the Fano factor from 1 evidently. The measured Fano factor for constitutive gene expression is slightly larger than 1, which is perhaps attributed to the time-delay effect.展开更多
基金supported by grants from the National Natural Science Foundation of China (No.30671060)Program for New Century Excellent Talent in Universities,China (No.NCET-07-0031)
文摘OBJECTIVE To study the effect of the Twist gene on the migration of human hepatocellular carcinoma cells and the possible mechanisms involved. METHODS RT-PCR was used to detect expression of the Twist gene in primary (Hep11) and recurrent (Hep12) cell lines from the same HCC patient. Hep11 cells were stably transfected with Twist-cDNA, and Hep12 cells were transiently transfected with Twist RNAi plasmid. Cell migration assays were performed on Twist up-regulated Hep11 cells and Twist RNAi Hep12 cells. RT- PCR and Western blot were used to test the expression of EMT markers. RESULTS Twist was expressed higher level and had increased migration capability in recurrent Hep12 cells than those in primary Hep11 cells. Cell models (Twist-Hep11) in which Twist protein was steadily and highly expressed were obtained. Compared with pcDNA3-Hep11 cells, migration of Twist-Hep11 cells was clearly increased. However, migration of Twist RNAi (Si-Twist-Hep12) Hep12 cells were reduced. Overexpression of Twist in Hep11 cells promoted expression of N-cad and vimentin. CONCLUSION These results indicate that Twist promotes the migration of hepatocellular carcinoma cells in vitro and may play an important role in the upregulation of mesenchymal markers.
基金supported by the IWK Health Centre, Nova Scotia Heath Research Foundation (NSHRF), Canadian Institute of Health Research (CIHR), the Atlee Endowment and NRC-Marine Biosciences
文摘The effects of clinically relevant doses of commonly prescribed stimulants methylphenidate (MPH), d-am- phetamine (d-AMPH), and dl-AMPH or mixed amphetamine salts (MAS) such as Adderall, on short- and long-term gene neuroadaptations in developing animals have not been widely investigated. In the present review, the effects of oral stimulant administration were compared with those of the subcutaneous or intra-peritoneal route. A selective set of stud- ies between 1979 and 2010, which incorporated in their design developmental period, clinically relevant doses of stimu- lants, and repeated daily doses were reviewed. These studies indicate that neuroadaptation to chronic stimulants includes blunting of stimulated immediate early gene expression, sensitivity of younger (prepubertal) brain to smaller dosages of stimulants, and the persistence of some effects, especially behavioral neuroadaptations, into adulthood. In addition, oral amphetamines (MAS) have more profound effects than does oral MPH. Further animal developmental studies are required to understand potential long-term neuroadaptations to low, daily oral doses of stimulants. Implications for clinical practice were also discussed.
文摘OBJECTIVE:To investigate the molecular effect of Socheongryong Tang(SCRT,Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology.METHODS:Asthma was induced by intranasal instillation of ovalbumin in mouse.After administration of SCRT on asthma-induced mouse,the expression of genes in lung tissue was measured using whole genome microarray.The functional implication of differentially expressed genes was performed using ontological analysis and the similarity of promoter structure of genes was also analyzed.RESULTS:Treatment of SCRT restored expression level of many up- or down-regulated genes in asthma model,and this recovery rate means SCRT could regulate a set of genes having specific TFBS binding sites.CONCLUSION:In this study,we identified a set of genes subjected to similar regulation by SCRT in asthma model in mice.
基金supported by the National Natural Science Foundation of China (31801094 to C.L. and 31771416 to X.L.)the Key Research Program of the Chinese Academy of Sciences (KFZD-SW-220-1 to X.L.)+3 种基金CAS “Light of West China” Program (to X.L.)the National Natural Science Foundation of China (31900417 to G.L.)the National Key Basic Research Program of China (2014CB542006 to C.L.)China Postdoctoral Science Foundation (2019M653162 to G.L.)。
文摘Buffering exogenous perturbation is crucial to maintain transcriptional homeostasis during development.While mi RNAs have been speculated to play a role in stability maintenance, previous studies seeking to check this conjecture focused on measurements of transcript levels at steady state or involved individual mi RNA targets. We measured whole-genome expression dynamics by introducing a transient perturbation and establishing a perturbation and recovery system in Drosophila larvae. We inhibited all transcription and assayed transcriptomes at several time points during recovery from inhibition. We performed these experiments in the wild type and mi RNA-deficient genetic backgrounds. Consistent with theories about mi RNAs’ function in stabilizing the transcriptome, we find that attenuating mi RNA expression leads to weak impairment in degradation of targets but strong destabilization of target genes when transcription is re-activated. We further fitted a model that captures the essential aspects of transcription dynamics in our experiments and found that the mi RNA target transcripts uniformly overshoot the original steady state as they recover from a general inhibition of transcription if global mi RNA levels are reduced. Collectively, our results provide experimental evidence for the idea that mi RNAs act cumulatively to stabilize the transcriptional regulatory network. We therefore found a promising approach to assess the effect of these molecules on transcription dynamics.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11405223 and 81370970by the Youth Innovation Promotion Association of Chinese Academy of Sciences
文摘The dynamics of constitutive gene expression with delayed m RNA degradation is investigated, where the intrinsic noise caused by the small number of reactant molecules is introduced. It is found that the oscillatory behavior claimed in previous investigations does not appear in the approximation of small time delay, and the steady state distribution still follows the Poisson law. Furthermore, we introduce the extrinsic noise induced by surrounding environment to explore the effects of this noise and time delay on the Fano factor. Based on a delay Langevin equation and the corresponding Fokker–Planck equation, the distribution of m RNA copy-number is achieved analytically. The time delay and extrinsic noise play similar roles in the gene expression system, that is, they are able to result in the deviation of the Fano factor from 1 evidently. The measured Fano factor for constitutive gene expression is slightly larger than 1, which is perhaps attributed to the time-delay effect.